Molecular and clinical characteristics of hepatitis B virus in Korea.
Korea is an endemic area of hepatitis B virus (HBV) infection but very little is known about the molecular characteristics of HBV isolates from Korean patients or the association with disease progression. The complete HBV genome sequences from 53 Korean patients with chronic hepatitis B, advanced cirrhosis, or hepatocellular carcinoma (HCC) were analyzed to identify (i) subgenotype distribution and genetic diversity and (ii) signature mutations associated with liver disease progression. With the exception of 1 patient infected with HBV/B, all 52 patients (98.1%) were infected with HBV/C, subgenotype C2. These strains were 98.4% identical and the frequency of amino acid substitutions occurring within key immunological epitopes increased with disease severity. A number of amino acid/nucleotide substitutions were associated with HCC, namely sR24K (HBsAg), SI126T (HBsAg), and pcA1846T (precore gene) mutations (P = 0.029, 0.001, and 0.008, respectively). HBV harboring deletions in the pre-S region were also associated with increased liver disease severity (chronic hepatitis B vs. cirrhosis, P = 0.040; chronic hepatitis B vs. HCC, P = 0.040). Despite the high degree of sequence conservation, several key HBV mutations were associated with disease progression. Prospective studies with larger cohorts of patients are required to evaluate further the clinical manifestation of HBV/C2 in Korea.
Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea.
Sang Hoon
SH
Ahn
Lilly
L
Yuen
Kwang-Hyub
KH
Han
Margaret
M
Littlejohn
Hye Young
HY
Chang
Hans
H
Damerow
Anna
A
Ayres
Jeong
J
Heo
Stephen
S
Locarnini
Peter A
PA
Revill
D000368:Aged; D019943:Amino Acid Substitution; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D016679:Genome, Viral; D006515:Hepatitis B virus / Q000145:classification / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000473:pathology* / Q000821:virology*; D006801:Humans; D008103:Liver Cirrhosis / Q000473:pathology*; D008113:Liver Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010802:Phylogeny; D056910:Republic of Korea; D055815:Young Adult