title: [The potential use of serum HBV RNA to guide the functional cure of chronic hepatitis B].
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.
authors.affiliation: Department of Microbiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: F M
authors.initials: FM
authors.lastname: Lu
authors.affiliation: Department of Microbiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Microbiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: X M
authors.initials: XM
authors.lastname: Chen
authors.affiliation: The Fist Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
authors.forename: J N
authors.initials: JN
authors.lastname: Jiang
authors.affiliation: Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: W H
authors.initials: WH
authors.lastname: Zhang
authors.affiliation: 302 Military Hospital, Beijing 100039, China.
authors.forename: J M
authors.initials: JM
authors.lastname: Zhao
authors.affiliation: The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
authors.forename: H
authors.initials: H
authors.lastname: Ren
authors.affiliation: Nanfang Hospital of Southern Medical University, Guangzhou 510515, China.
authors.forename: J L
authors.initials: JL
authors.lastname: Hou
authors.affiliation: National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen 361102, China.
authors.forename: N S
authors.initials: NS
authors.lastname: Xia
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D004270:DNA, Circular / Q000097:blood; D004279:DNA, Viral / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000188:drug therapy*; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D012367:RNA, Viral / Q000097:blood*
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D004270:DNA, Circular; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D012367:RNA, Viral
keywords: Antiviral therapy; Functional cure; Hepatitis B, chronic; Safe discontinuation; Serum HBV RNA; cccDNA