HBsAg Seroclearance in chronic hepatitis B in Asian patients: replicative level and risk of hepatocellular carcinoma.
OBJECTIVE
Our aims were to study the virologic, histologic, and clinical outcome in chronic hepatitis B (CHB) patients with hepatitis B surface antigen (HBsAg) seroclearance.


METHODS
We determined the age of HBsAg seroclearance that is associated with a lower risk for hepatocellular carcinoma (HCC) in 298 CHB patients (median follow-up, 108 months). The following virologic and histologic features were also determined: liver stiffness (n = 229), liver histology, serum HBV DNA levels over time (n = 265), intrahepatic HBV DNA with covalently closed circular DNA (cccDNA) levels, and messenger RNA (mRNA) expression.


RESULTS
The median age of HBsAg seroclearance was 49.6 years. Seven (2.4%) patients developed HCC. Cumulative risk for HCC was higher in patients with HBsAg seroclearance at ages >or=50 years compared with those with HBsAg seroclearance at ages <50 (P = .004) years. Of these 2 groups of patients, 29.5% and 7.9%, respectively, had significant fibrosis by liver stiffness measurement (P = .001), and 15.4% of patients had mild histologic fibrosis. Intrahepatic total HBV DNA and cccDNA were detected in 100% and 79.3% of patients, respectively. All patients had undetectable surface and precore/pregenomic RNA transcripts. One (9.1%) patient had X mRNA expression. Serum HBV DNA were detectable in 13.4%, 6.1%, and 3.7% of patients within 1 year and 5-10 and >10 years after HBsAg seroclearance, respectively, and 82.1% patients had persistently normal alanine aminotransferase levels.


CONCLUSIONS
HBV persisted at low replicative and transcriptional levels after HBsAg seroclearance. HBsAg seroclearance at age <50 years was associated with a lower risk for the development of HCC.
Yuen
Man-Fung
MF
Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong. mfyuen@hkucc.hku.hk
Wong
Danny Ka-Ho
DK
Fung
James
J
Ip
Philip
P
But
David
D
Hung
Ivan
I
Lau
Kevin
K
Yuen
John Chi-Hang
JC
Lai
Ching-Lung
CL
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000706:statistics & numerical data*; D006528:Carcinoma, Hepatocellular / Q000208:ethnology* / Q000473:pathology / Q000821:virology*; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006510:Hepatitis B Antibodies / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D019694:Hepatitis B, Chronic / Q000208:ethnology* / Q000276:immunology / Q000473:pathology; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D007223:Infant; D008099:Liver / Q000473:pathology / Q000821:virology; D008103:Liver Cirrhosis / Q000208:ethnology / Q000473:pathology / Q000821:virology; D008113:Liver Neoplasms / Q000208:ethnology* / Q000473:pathology / Q000821:virology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D016036:Seroepidemiologic Studies
D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens