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World J Gastroenterol. Feb 14, 2011; 17(6): 708-716
Published online Feb 14, 2011. doi: 10.3748/wjg.v17.i6.708
Association of core promoter mutations of hepatitis B virus and viral load is different in HBeAg(+) and HBeAg(-) patients
Andi Utama, Marlinang Diarta Siburian, Sigit Purwantomo, Mariana Destila Bayu Intan, Tri Shinta Kurniasih, Rino Alvani Gani, Wenny Astuti Achwan, Arnelis, Syafruddin AR Lelosutan, Benyamin Lukito, Tantoro Harmono, Nasrul Zubir, Julius, Soewignjo Soemohardjo, Laurentius Adrianus Lesmana, Ali Sulaiman, Susan Tai
Andi Utama, Marlinang Diarta Siburian, Sigit Purwantomo, Mariana Destila Bayu Intan, Tri Shinta Kurniasih, Susan Tai, Molecular Epidemiology Division, Mochtar Riady Institute for Nanotechnology, Universitas Pelita Harapan, Lippo Karawaci, Tangerang, 15810, Indonesia
Rino Alvani Gani, Laurentius Adrianus Lesmana, Ali Sulaiman, Hepatology Division, Department of Internal Medicine, Faculty of Medicine, University of Indonesia, Jakarta, 10430, Indonesia
Wenny Astuti Achwan, Soewignjo Soemohardjo, Department of Internal Medicine, Mataram General Hospital, Mataram, 83127, Indonesia
Arnelis, Nasrul Zubir, Julius, Gastroentero-Hepatology Division, Department of Internal Medicine, Dr. M. Jamil Hospital, Padang, 25127, Indonesia
Syafruddin AR Lelosutan, Gastroentero-Hepatology Division, Department of Internal Medicine, Dr. Gatot Soebroto Hospital, Jakarta, 10410, Indonesia
Benyamin Lukito, Department of Internal Medicine, Siloam Hospital Lippo Village, Tangerang, 15810, Indonesia
Tantoro Harmono, Department of Internal Medicine, Dr. Moewardi Hospital, Surakarta, 57126, Indonesia
Author contributions: Utama A, Siburian MD and Purwantomo S designed and performed the experiments; Intan MDB and Kurniasih TS performed some experiments; Tai S was involved in experiment design and editing the manuscript; Gani RA, Achwan WA, Arnelis, Zubir N, Julius, Soemoharjo S, Lelosutan SAR, Lukito B, Harmono T, Lesmana LA and Sulaiman A coordinated and provided the collection of human materials and were involved in editing the manuscript.
Supported by MRIN Funding (Budget No. cc041/2009)
Correspondence to: Andi Utama, PhD, Molecular Epidemiology Division, Mochtar Riady Institute for Nanotechnology, Universitas Pelita Harapan, Jalan Boulevard Jend. Sudirman 1688, Lippo Karawaci, Tangerang 15810, Banten, Indonesia. autama@mrinstitute.org
Telephone: +62-21-54210123 Fax: +62-21-54210110
Received: September 1, 2010
Revised: November 25, 2010
Accepted: December 2, 2010
Published online: February 14, 2011
AIM: To identify the prevalence of hepatitis B e antigen (HBeAg) and to assess the association of hepatitis B virus (HBV) core promoter mutations and viral load in Indonesian patients.
METHODS: Sixty-four patients with chronic hepatitis, 65 with liver cirrhosis and 50 with hepatocellular carcinoma were included in this study. HBeAg and hepatitis B e antibody (HBeAb) tests were performed using enzyme-linked immunosorbent assay and the mutations were analyzed by sequencing. Viral load was measured by real-time polymerase chain reaction.
RESULTS: Of 179 patients, 108 (60.3%) were HBeAg(-) and 86 (79.6%) of these HBeAg(-) patients had been seroconverted. The A1896 mutation was not found in HBeAg(+) patients, however, this mutation was detected in 70.7% of HBeAg(-) patients. This mutation was frequently found when HBeAg was not expressed (87.7%), compared to that found in HBeAg seroconverted patients (65.1%). The A1899 mutation was also more prevalent in HBeAg(-) than in HBeAg(+) patients (P = 0.004). The T1762/A1764 mutation was frequently found in both HBeAg(+) and HBeAg(-) patients, however, the prevalence of this mutation did not significantly differ among the two groups (P = 0.054). In HBeAg(+) patients, the T1762/A1764 mutation was correlated with lower HBV DNA (P < 0.001). The A1899 mutation did not correlate with HBV DNA (P = 0.609). In HBeAg(-) patients, the T1762/A1764 mutation alone was not correlated with HBV DNA (P = 0.095), however, the presence of either the T1762/A1764 or A1896 mutations was associated with increased HBV DNA (P < 0.001).
CONCLUSION: The percentage of HBeAg(-) patients is high in Indonesia, and most of the HBeAg(-) patients had been seroconverted. The A1896 mutation was most likely the major cause of HBeAg loss. The T1762/A1764 mutation alone was associated with lower viral loads in HBeAg(+) patients, but not in HBeAg(-) patients.
