The potential use of serum HBV RNA to guide the functional cure of chronic hepatitis B
10.3760/cma.j.issn.1007-3418.2017.02.005
- VernacularTitle: 乙型肝炎病毒RNA病毒样颗粒的发现及其对抗病毒治疗临床实践的潜在影响
- Author:
Fengmin LU
1
;
Jie WANG
1
;
Xiangmei CHEN
1
;
Jianning JIANG
2
;
Wenhong ZHANG
3
;
Jingmin ZHAO
4
;
Hong REN
5
;
Jinlin HOU
6
;
Ningshao XIA
7
Author Information
1. Department of Microbiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
2. The Fist Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
3. Huashan Hospital, Fudan University, Shanghai 200040, China
4. 302 Military Hospital, Beijing 100039, China
5. The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
6. Nanfang Hospital of Southern Medical University, Guangzhou 510515, China
7. National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen 361102, China
- Publication Type:Journal Article
- Keywords:
Hepatitis B, chronic;
Antiviral therapy;
Serum HBV RNA;
cccDNA;
Safe discontinuation;
Functional cure
- From:
Chinese Journal of Hepatology
2017;25(2):105-110
- CountryChina
- Language:Chinese
-
Abstract:
Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) in infected hepatocytes is the main cause of off-therapy viral rebound. The half-life of cccDNA is only 33-50 days, so the conversion of newly synthesized rcDNA to cccDNA in the nucleus is essential for the maintenance of cccDNA pool in infected hepatocytes. Though not directly targeting the existing cccDNA, current nucleos(t)ide analogues (NAs) may exhaust the cccDNA reservoir by blocking the rcDNA formation. Indeed, a prolonged consolidation therapy post loss of serum HBV DNA can achieve sustained remission and thus safe drug discontinuation in a small proportion of chronic hepatitis B (CHB) patients. In recent studies, we and others have demonstrated that it is the serum HBV RNA that reflects the cccDNA activity in infected hepatocytes, particularly among the patients on NAs. Here we suggest that instead of measuring serum HBV DNA only, simultaneous measurement of both viral DNA and RNA would improve the accuracy to reflect the cccDNA activity; therefore, the virological response should be redefined as consistent loss (less than the lower limit of detection) of both serum HBV DNA and RNA, which indicates the safety of drug discontinuation. Accumulating evidence has suggested that for the CHB patients with lower serum HBsAg, switch-to or add-on pegylated interferon (Peg-IFN) treatment would result in loss of serum HBsAg in a relatively large proportion of CHB patients. Since serum HBV RNA is an ideal biomarker to reflect the intrahepatic cccDNA activity, for the patients with a serum HBsAg level lower than 1 500 IU/ml after long-term NAs treatment, the serum HBV RNA should be measured. If serum HBV RNA is detected, peg-IFN should be added on; if serum HBV RNA is not detected, NAs treatment should be switched to peg-IFN treatment. We believe the therapy based on serum HBV RNA would make the functional cure of CHB (serum HBsAg loss or even conversion to anti-HBs) more efficient.
