Off-Treatment Hepatitis B Virus (HBV) DNA Levels and the Prediction of Relapse After Discontinuation of Nucleos(t)ide Analogue Therapy in Patients With Chronic Hepatitis B: A Prospective Stop Study.
The optimal management remains unknown after nucleos(t)ide analogue (NA) discontinuation in patients with chronic hepatitis B (CHB). This prospective study investigated the role of off-treatment viral kinetics in predicting relapse after discontinuation of NA therapy.



A total of 82 noncirrhotic Asian patients with CHB who discontinued NA therapy according to international guidelines were prospectively followed. Patients with a hepatitis B virus (HBV) DNA level of >2000 IU/mL and an alanine aminotransferase (ALT) level of >2 times the upper limit of normal (clinical relapse) were retreated.



Sixty patients were HBV envelope antigen (HBeAg) positive at the start of treatment, and 22 were HBeAg negative. Clinical relapse developed in 28 patients (2-year rates, 31% among HBeAg-positive patients and 53% among HBeAg-negative patients). Age of ≤35 years (hazard ratio [HR], 0.37; P = .026) and end-of-treatment HBsAg level of ≤200 IU/mL (HR, 0.39; P = .078) were independently associated with lower relapse rates. A high risk of biochemical relapse (defined as an ALT level of >2 times the upper limit of normal) was observed if the HBV DNA level was >200000 IU/mL when the level was initially elevated, compared with HBV DNA levels of >2000 to ≤200000 IU/mL (HR, 8.42; P < .001). The risk of biochemical relapse was also high in patients with persistent elevation in the HBV DNA level (confirmed to be >2000 IU/mL within 3 months), compared with the group with transient elevation (HR, 6.87; P < .001).



After NA discontinuation, a lower relapse rate was observed in younger patients and in those with low end-of-treatment HBsAg levels. The level and persistence of off-treatment elevated HBV DNA levels were useful in the prediction of a subsequent biochemical relapse and may thus be used to guide off-treatment management.
Department of Infectious Diseases, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Jiawei
J
Cao
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, The Netherlands.
Heng
H
Chi
Department of Infectious Diseases, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Tao
T
Yu
Department of Infectious Diseases, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Zhandong
Z
Li
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, The Netherlands.
Bettina E
BE
Hansen
Department of Infectious Diseases, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Xiaoyong
X
Zhang
Department of Infectious Diseases, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Chunxiu
C
Zhong
Department of Infectious Diseases, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Jian
J
Sun
Department of Infectious Diseases, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Jinlin
J
Hou
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, The Netherlands.|Toronto Centre of Liver Disease, University Health Network, Toronto General Hospital, University of Toronto, Canada.
Harry L A
HLA
Janssen
Department of Infectious Diseases, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Jie
J
Peng
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000494:pharmacology*; D044466:Asian People; D004279:DNA, Viral / Q000302:isolation & purification*; D023381:Endpoint Determination; D005260:Female; D005500:Follow-Up Studies; D006514:Hepatitis B Surface Antigens / Q000097:blood / Q000276:immunology; D006513:Hepatitis B e Antigens / Q000097:blood / Q000276:immunology; D006515:Hepatitis B virus / Q000187:drug effects / Q000302:isolation & purification*; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D057230:Limit of Detection; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009705:Nucleosides / Q000494:pharmacology*; D009711:Nucleotides / Q000494:pharmacology*; D011446:Prospective Studies; D012008:Recurrence; D012307:Risk Factors; D016896:Treatment Outcome
D000998:Antiviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D009705:Nucleosides; D009711:Nucleotides; D000410:Alanine Transaminase
Treatment cessation; antiviral agents; hepatitis B; off-treatment management