Hepatitis B virus (HBV) DNA replication was suppressed and liver inflammation improved in patients with chronic HBV who were treated with long-term nucleos(t)ide analogue (NA) therapy: After 1 year of NA treatment, patients who were HBV pregenomic RNA (pgRNA)-positive required more time to achieve an undetectable HBV DNA load and hepatitis B e antigen (HBeAg) clearance than patients who were HBV pgRNA-negative, according to a study published in the Journal of Viral Hepatitis.
Researchers of this cohort study investigated dynamic changes in HBV DNA and HBeAg status in patients with chronic HBV during NA treatment. The 103 participants who were treatment-naive were categorized according to whether they were HBV pgRNA-negative or HBV pgRNA-positive after NA treatment for 48 weeks. Participants received routine biochemical tests twice a year for 7 years. Over the course of the 7-year study, 21 patients discontinued therapy for various reasons, primarily unwillingness to commit to long-term treatment.
After 48 weeks of treatment, 28 of 58 (48.28%) of HBV DNA undetectable participants were still HBV pgRNA positive, and 5 of 40 (12.5%) HBV DNA detectable participants became HBV pgRNA undetectable. Participants were then divided into HBV pgRNA-negative or HBV pgRNA-positive groups, with 5 patients excluded because of serum sample defects. Of the 98 participants remaining, 63 (64.29%) had detectable HBV pgRNA, and in 35 patients (35.71%), HBV pgRNA was undetectable. More participants in the HBV pgRNA-positive group had also been HBeAg-positive before treatment, and their baseline HBV DNA loads were significantly higher compared with the other group (8.08±1.08 vs 6.64±1.66). Significantly more participants who were HBV pgRNA-negative exhibited HBeAg clearance than those who were HBV pgRNA-positive (19/35 vs 19/63).
After treatment, HBV pgRNA status was significantly different between participants who did achieve HBeAg clearance compared with those who did not (χ²=78), and the logistic regression model showed an association between HBV pgRNA positivity and an increased risk of not clearing HBeAg (hazard ratio, 6.69; 95% CI, 1.88-23.84). Participants who were categorized as being HBV pgRNA-positive experienced a significantly longer median time to HBeAg clearance than those in the HBV pgRNA-negative group (152 weeks; 95% CI, 93.34-210 vs 72 weeks; 95% CI, 34.91-109). Participants who were categorized as being HBV pgRNA-positive also required more time to reach undetectable HBV DNA loads (124 weeks; 95% CI, 103.33-144-67 vs 48 weeks; 95% CI, 34.80-61.20).
Study investigators stated, “In conclusion, HBV DNA replication was suppressed, and liver inflammation was improved in CHB patients during oral antiviral therapy. Patients who were HBV pgRNA-positive after NA treatment were less likely to achieve HBeAg clearance and needed more time to achieve HBeAg clearance and an undetectable HBV DNA load than those who were HBV pgRNA-negative after 1 year of NA treatment.”
Luo H, Tan N, Kang Q, et al. Hepatitis B virus pregenomic RNA status can reveal the long-term prognoses of chronic hepatitis B patients treated with nucleos(t)ide analogues [published online October 31, 2019]. J Viral Hepat. doi: 10.1111/jvh.13227