Treatment cessation of entecavir in Asian patients with hepatitis B e antigen negative chronic hepatitis B: a multicentre prospective study.
OBJECTIVE
The off-treatment durability of nucleos(t)ide analogue therapy in Asian hepatitis B e antigen (HBeAg) negative chronic hepatitis B (CHB) and the role of hepatitis B surface antigen (HBsAg) levels in predicting off-treatment durability has not been well investigated.


METHODS
Following Asia-Pacific Association for the Study of the Liver guidelines, entecavir was stopped in Asian HBeAg negative patients treated for ≥ 2 years with undetectable HBV DNA levels on ≥ 3 separate occasions 6 months apart before treatment cessation. HBsAg and HBV DNA levels were prospectively monitored every 6-12 weeks for 48 weeks. Entecavir was restarted if there was virologic relapse (defined as HBV DNA >2000IU/mL).


RESULTS
184 patients (mean age 53.9 years, 67.9% male) were recruited. The cumulative rate of virologic relapse at 24 and 48 weeks was 74.2% and 91.4%, respectively. The median HBV DNA level at virologic relapse was 11000 (range 2115 to >1.98×10(8)) IU/mL. 42 (25.8%) patients had elevated alanine aminotransferase (median level 97 U/L, range 37-1058 U/L) during virologic relapse. Mean rate of off-treatment HBsAg decline was 0.018 (± 0.456) log IU/mL/year. No patients cleared HBsAg. There was no correlation between off-treatment serial HBsAg and HBV DNA levels (r=-0.026, p=0.541). HBsAg levels at the time of entecavir commencement, entecavir cessation and the subsequent rate of HBsAg reduction were not associated with virologic relapse (all p>0.05).


CONCLUSIONS
Entecavir cessation in Asian HBeAg negative CHB resulted in high rates of virologic relapse, suggesting nucleos(t)ide analogue therapy should be continued indefinitely until the recognised treatment endpoint of HBsAg seroclearance.
Department of Medicine, The University of Hong Kong, Hong Kong.
Wai-Kay
WK
Seto
Department of Medicine, Alice Ho Miu Ling Nethersole Hospital, Hong Kong.
Aric Josun
AJ
Hui
Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong.
Vincent Wai-Sun
VW
Wong
Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong.
Grace Lai-Hung
GL
Wong
Department of Medicine, The University of Hong Kong, Hong Kong.
Kevin Sze-Hang
KS
Liu
Department of Medicine, The University of Hong Kong, Hong Kong.
Ching-Lung
CL
Lai
Department of Medicine, The University of Hong Kong, Hong Kong.
Man-Fung
MF
Yuen
Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong.
Henry Lik-Yuen
HL
Chan
D000998:Antiviral Agents / Q000008:administration & dosage*; D044466:Asian People; D005260:Female; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012008:Recurrence; D028761:Withholding Treatment
D000998:Antiviral Agents; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; C413685:entecavir; D006147:Guanine
ANTIVIRAL THERAPY; HEPATITIS B; LIVER