High frequency of the 1896 precore mutation in patients and blood donors with hepatitis B virus infection from the Indian subcontinent.
OBJECTIVE
Hepatitis B virus (HBV) e antigen (HBeAg)-negative variants are reported to harbor 1896 precore mutants, and predict a worse clinical outcome. The aim of this study was to estimate the incidence of a precore mutation (1896) in both patients with chronic hepatitis B (CH-B) infection and blood donors in a tertiary care hospital in south India.


METHODS
One hundred and twenty-two consecutive HBV DNA-positive CH-B patients (group I) and 102 HBsAg-positive 'healthy' blood donors (group II) were recruited. Samples found to be positive for HBV DNA were further studied. A nested PCR was used for the detection of HBV DNA. The 1896 precore mutation was detected using PCR-restriction fragment length polymorphism (RFLP). Nucleotide sequencing was performed on representative samples to confirm PCR-RFLP findings. The study population was stratified comprising: group IA: 17 HBeAg-positive CH-B patients; group IB: 105 HBeAg-negative CH-B patients; group IIA: 12 HBeAg-positive blood donors; and group IIB: 55 HBeAg-negative blood donors.


RESULTS
There was no significant difference in the HBeAg-positive status between groups I and II. Significantly higher levels of alanine transaminase (ALT) were seen in groups IA and IB than in groups IIA and IIB, respectively (p = 0.033; p = 0.004). A significantly higher proportion of CH-B patients (32.7%) were positive for anti-HBc IgM compared with the blood donor groups (10.4%; p = 0.0006). Among the HBeAg-negative subjects, 69% of the CH-B patients and 65% of the blood donors showed evidence of 1896 precore mutant. This infection included the 1896 mutant exclusively or mixed infection involving the 1896 mutant and 1896 wild-type.


CONCLUSIONS
The absence of detectable HBeAg in most of the viremic blood donors and patients emphasizes the need for HBV DNA testing irrespective of HBeAg status. Mixed infection was detected in a higher proportion (42.6%) of CH-B patients than in blood donors (26.8%; p = 0.031). Among those with mixed infection, a significant proportion (44.2%) of CH-B patients, had ALT levels greater than the upper limit of normal (ULN), as compared with the blood donor groups (16.6%; p = 0.036).


CONCLUSIONS
The majority of CH-B patients and blood donors were negative for HBeAg despite their positive HIV DNA status. About two-thirds of the HBsAg-positive blood donors were viremic. Mixed infection was detected more frequently in CH-B patients and appears to be associated with more pronounced liver damage, as indicated by increased ALT levels.
Vivekanandan
Perumal
P
Department of Clinical Virology, Christian Medical College, Vellore, India.
Abraham
Priya
P
Sridharan
Gopalan
G
Chandy
George
G
Shaji
Ramachandran V
RV
Daniel
Dolly
D
Raghuraman
Sukanya
S
Daniel
Hubert Darius
HD
Subramaniam
Thenmozhi
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D001782:Blood Donors; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000097:blood / Q000235:genetics; D005260:Female; D005814:Genes, Viral; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000201:enzymology / Q000821:virology*; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis
D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D000410:Alanine Transaminase