Serum HBV RNA and HBeAg are useful markers for the safe discontinuation of nucleotide analogue treatments in chronic hepatitis B patients

• Published in: Journal of gastroenterology Vol. 48; no. 10; pp. 1188 - 1204
• Main Authors: Tsuge, Masataka, Murakami, Eisuke, Imamura, Michio, Abe, Hiromi, Miki, Daiki, Hiraga, Nobuhiko, Takahashi, Shoichi, Ochi, Hidenori, Nelson Hayes, C., Ginba, Hiroyuki, Matsuyama, Kazuhiro, Kawakami, Hiroiku, Chayama, Kazuaki
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01-10-2013; Springer; Springer Nature B.V
• Subjects: Abdominal Surgery; Adefovir dipivoxil; Adult; Aged; Alanine transaminase; Alanine Transaminase - blood; Analysis; Antiviral Agents - administration & dosage; Biliary Tract; Biomarkers - blood; Colorectal Surgery; Development and progression; DNA; DNA, Viral - blood; Drug therapy; Female; Gastroenterology; Hepatitis B; Hepatitis B e Antigens - blood; Hepatitis B virus; Hepatitis B virus - genetics; Hepatitis B, Chronic - blood; Hepatitis B, Chronic - drug therapy; Hepatology; Humans; Japan; Male; Medical research; Medicine; Medicine & Public Health; Medicine, Experimental; Middle Aged; Original Article—Liver; Pancreas; Real-Time Polymerase Chain Reaction; Recurrence; RNA; RNA, Viral - blood; Surgical Oncology; Japan; Nucleotide analogue; HBV replication; HBV; HBV RNA
• ISSN: 0944-1174; 1435-5922
• DOI: 10.1007/s00535-012-0737-2

Background
Treatment for chronic hepatitis B has improved drastically with the use of nucleot(s)ide analogues (NAs). However, NA therapy typically fails to eliminate Hepatitis B virus (HBV) completely, and it is difficult to discontinue these therapies. We previously demonstrated that NA therapy induced immature viral particles, including HBV RNA in sera of chronic hepatitis B patients. In the study reported here, we analyzed the association between HBV RNA titer and the recurrence rate of hepatitis after discontinuation of NA therapy.
Methods
The study cohort comprised 36 patients who had discontinued NA therapy. Serum HBV DNA or DNA plus RNA levels were measured by real time PCR and statistical analyses were performed using clinical data and HBV markers.
Results
At 24 weeks after discontinuation of NA therapy, HBV DNA rebound was observed in 19 of the 36 patients (52.8 %), and alanine aminotransferase (ALT) rebound was observed in 12 of 36 patients (33.3 %). Multivariate statistical analysis was used to identify factors predictive of HBV DNA rebound. The HBV DNA + RNA titer following 3 months of treatment was significantly associated with HBV DNA rebound [
P
 = 0.043, odds ratio (OR) 9.474, 95 % confidence interval (CI) 1.069–83.957)]. Absence of hepatitis B e antigen (HBeAg) at the end of treatment was significantly associated with ALT rebound (
P
 = 0.003, OR 13.500, 95 % CI 2.473–73.705). In HBeAg-positive patients, the HBV DNA + RNA titer after 3 months of treatment was marginally associated with ALT rebound (
P
 = 0.050, OR 8.032, 95 % CI 0.997–64.683).
Conclusions
Monitoring of serum HBV DNA + RNA levels may be a useful method for predicting re-activation of chronic hepatitis B after discontinuation of NA therapy.