A 13-year longitudinal study of the impact of double mutations in the core promoter region of hepatitis B virus on HBeAg seroconversion and disease progression in patients with genotype C chronic active hepatitis.
The pathogenic role of core promoter (CP) mutations (T1762/A1764) of hepatitis B virus (HBV) in hepatitis B e antigen (HBeAg) seroconversion or disease progression remains unclear. We investigated the clinical relevance of these mutants over a long-term follow-up period of up to 15 years. In this longitudinal cohort study, 29 HBeAg-positive patients with biopsy-proved chronic active hepatitis without cirrhosis were regularly monitored for >10 years. The viral isolates were characterized, using the frozen liver tissue obtained on the day of biopsy. Long-term outcomes were compared between patients with and without CP mutations of HBV at baseline. HBV genotyping showed that 100% of study subjects were infected with genotype C HBV. During a median follow-up period of 12.5 years, patients without double CP mutations of HBV at baseline showed a tendency towards achieving an earlier HBeAg seroconversion than those with (6.9 vs 9.4 years, P = 0.062) double CP mutations. Double CP mutations at baseline were also significantly associated with the eventual development of cirrhosis or hepatocellular carcinoma (P = 0.013), whereas the absence of double CP mutations predicted inactive carrier status at the last follow-up (P = 0.027). At 10 years, liver-related tests were also significantly better in patients without double CP mutations of HBV than in those with these mutations, as reflected by higher platelet counts and albumin levels (P = 0.036 and P = 0.044, respectively). Double T1762/A1764 mutations are significantly related to liver deterioration in HBeAg-positive genotype C active hepatitis patients. A longer period of immune clearance coupled with delayed HBeAg seroconversion appears to contribute to disease progression in patients harbouring these mutations in the CP region of HBV.
Jang
J W
JW
Department of Internal Medicine, College of Medicine, Seoul, South Korea.
Lee
Y C
YC
Kim
M S
MS
Lee
S Y
SY
Bae
S H
SH
Choi
J Y
JY
Yoon
S K
SK
D000293:Adolescent; D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000821:virology; D002353:Carrier State / Q000821:virology; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006510:Hepatitis B Antibodies / Q000097:blood*; D006513:Hepatitis B e Antigens / Q000097:blood / Q000276:immunology*; D006515:Hepatitis B virus / Q000235:genetics*; D006521:Hepatitis, Chronic / Q000150:complications / Q000276:immunology / Q000473:pathology / Q000821:virology*; D006801:Humans; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000821:virology; D008111:Liver Function Tests; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011401:Promoter Regions, Genetic
D006510:Hepatitis B Antibodies; D006513:Hepatitis B e Antigens