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Predictive value of precore hepatitis B virus mutations in spontaneous and interferon‐induced hepatitis B e antigen clearance
Author(s) -
Lok Anna S. F.,
Akarca Ulus S.,
Greene Sheila
Publication year - 1995
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840210105
Subject(s) - virology , hepatitis b virus , interferon , predictive value , antigen , hepatitis b , medicine , virus , immunology
We previously reported two mutually exclusive mutations in the precore region of hepatitis B virus: M1 (T‐1856, proline‐serine substitution at codon 15) and M2 (A‐1896, stop codon at codon 28). This study was conducted to determine if the presence of precore mutants affect spontaneous or interferon (IFN)‐induced hepatitis B e antigen (HBeAg) clearance. Sera from 201 hepatitis B e antigen posititis B virus (HBV) infection were analyzed by direct sequencing of HBV DNA after amplification by polymerase chain reaction (PCR) assay. Forty‐three (21%) patients had M1 (T‐1856), and 20 patients (10%) had M2 (A‐1896). During a follow‐up period of 1 to 7 years, 75%, 28%, and 26% of those with M2 (A‐1896), M1 (T‐1856), and wild type sequence respectively, cleared HBeAg ( P <.0001). Eighteen (67%) of 27 patients with wild‐type sequence but none of 10 patients who had M1 (T‐1856) in their initial samples developed M2 (A‐1896) after loss of HBeAg ( P <.0001). Sustained antiviral response was achieved in 55%, 0%, and 17% of interferontreated patients who had M2 (A‐1896), M1 (T‐1856), and wild‐type sequence, respectively, initially ( P = 0.04). However, patients with M2 (A‐1896) were also more likely to have elevated pretreatment aminotransferase levels ( P = 0.02). In summary, HBeAg‐positive Chinese patients with M2 (A‐1896) were more likely to clear HBeAg, and to do so earlier. Neverthless, development or selection of M2 (A‐1896) was not a prerequisite for HBeAg clearance. Interferon therapy did not increase the rate of HBeAg clearance in patients with M2 (A‐1896) when stratified for aminotransferase levels. (Hepatology 1995;21:19–24).