title: Naturally occurring core immune-escape and carboxy-terminal mutations\truncations in patients with e antigen negative chronic hepatitis B.
abstract: BACKGROUND
  Hepatocellular injury is often progressive in patients with hepatitis B e antigen negative chronic hepatitis B (HBeAg -ve CHB). There is scant data on association of core mutations occurring in patients with HBeAg -ve CHB with severity of liver disease.
  
  
  METHODS
  Hundred and eighteen patients with chronic infection who were HBeAg negative, anti-HBe, and HBV DNA positive were enrolled. Precore and core regions were amplified, sequenced, and analyzed for precore, T helper, cytotoxic T lymphocytes (CTLs), B-cell epitope, and core carboxy-terminal region mutations.
  
  
  RESULTS
  Majority of patients were infected with HBV genotype D: 96 (81%) [D1: 16, D2: 55 and D5: 25] followed by genotype A1: 15 (13%) and genotype C: 7 (6%) [C1: 5 and unidentified subgenotype C: 2]. Classical (A1896) as well as nonclassical precore region mutations were detected in 30 (25%) and in 9 (7.6%) patients, respectively. Core immune escape, core carboxy-terminal mutations and truncations were detected in 61 (52%), 11 (9.3%), and 14 (12%) patients, respectively. Three core immune escape mutations were significantly higher in patients with coexisting precore stop codon compared with patients without precore stop codon mutation, cT12S (43 vs. 8%, p < 0.001), cS21T (16 vs. 3.4%, p < 0.026), and cE77D (30 vs. 4.5%, p < 0.002). When frequency of core immune escape mutations was compared among CHB and decompensated patients, and cT12S: (27 vs. 10%, p < 0.05), cS21T (16 vs. 1.35%, p < 0.01), cT67P/N: (20 vs. 4%, p < 0.001), cE113D (11.37 vs. 1.35%, p < 0.05), and cP130T/Q (7 vs. 0%, p < 0.001) mutations were found to be significantly higher in decompensated patients.
  
  
  CONCLUSIONS
  Core immune-escape mutations cT12S, cS21T, cT67P, cE113D, and cP130T/Q are significantly higher in decompensated liver disease patients and could influence the severity of liver disease in HBeAg -ve CHB patients.
authors.affiliation: Department of Gastroenterology and Advanced Centre for Liver Diseases, G.B. Pant Hospital, Room No. 201, New Delhi, 110002, India.|Department of Biochemistry, Lady Hardinge Medical College, New Delhi, 110002, India.
authors.forename: Ranjit
authors.initials: R
authors.lastname: Chauhan
authors.affiliation: Department of Gastroenterology and Advanced Centre for Liver Diseases, G.B. Pant Hospital, Room No. 201, New Delhi, 110002, India. sksarin@nda.vsnl.net.in.
authors.forename: Shiv K
authors.initials: SK
authors.lastname: Sarin
authors.affiliation: Department of Gastroenterology and Advanced Centre for Liver Diseases, G.B. Pant Hospital, Room No. 201, New Delhi, 110002, India.
authors.forename: Manoj
authors.initials: M
authors.lastname: Kumar
authors.affiliation: Department of Biochemistry, Lady Hardinge Medical College, New Delhi, 110002, India.
authors.forename: Jayashree
authors.initials: J
authors.lastname: Bhattacharjee
keywords: Carboxy-terminal; Core; Genotype; HBV; HBeAg; Immune-escape; Mutation