Naturally occurring core immune-escape and carboxy-terminal mutations\truncations in patients with e antigen negative chronic hepatitis B.

Abstract

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. 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. 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. 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.