Hepatitis B virus pre-S2 start codon mutations in Indonesian liver disease patients.
OBJECTIVE
To identify the prevalence of pre-S2 start codon mutations and to assess their association with liver disease progression.


METHODS
The mutations were identified by direct sequencing from 73 asymptomatic carriers, 66 chronic hepatitis (CH), 66 liver cirrhosis (LC) and 63 hepatocellular carcinoma (HCC) patients. Statistical significances were determined using Fisher's exact test, χ² test, and t-test analyses whenever appropriate. Pre-S mutation as a risk factor for advanced liver disease was estimated by unconditional logistic regression model adjusted with age, sex, and hepatitis B e antigen (HBeAg). P < 0.05 was considered significant.


RESULTS
Mutation of the hepatitis B virus (HBV) pre-S2 start codon was found in 59 samples from 268 subjects (22.0%), with higher prevalence in patients with cirrhosis 27/66 (40.9%) followed by HCC 18/63 (28.6%), chronic hepatitis 12/66 (18.2%) and asymptomatic carriers 2/73 (2.7%) (P < 0.001). Logistic regression analysis showed that pre-S2 start codon mutation was an independent factor for progressive liver disease. Other mutations, at T130, Q132, and A138, were also associated with LC and HCC, although this was not statistically significant when adjusted for age, sex, and HBeAg. The prevalence of pre-S2 start codon mutation was higher in HBV/B than in HBV/C (23.0% vs 19.1%), whilst the prevalence of T130, Q132, and A138 mutation was higher in HBV/C than in HBV/B. The prevalence of pre-S2 start codon mutation was higher in LC (38.9%) and HCC (40.0%) than CH (5.6%) in HBeAg⁺ group, but it was similar between CH, LC and HCC in HBeAg⁻ group.


CONCLUSIONS
Pre-S2 start codon mutation was higher in Indonesian patients compared to other Asian countries, and its prevalence was associated with advanced liver disease, particularly in HBeAg⁺ patients.
Molecular Epidemiology Division, Mochtar Riady Institute for Nanotechnology, Universitas Pelita Harapan, Lippo Karawaci, Tangerang 15810, Banten, Indonesia. autama@mrinstitute.org
Andi
A
Utama
Marlinang Diarta
MD
Siburian
Ismail
I
Fanany
Mariana Destila Bayu
MD
Intan
Rama
R
Dhenni
Tri Shinta
TS
Kurniasih
Syafruddin A R
SA
Lelosutan
Wenny Astuti
WA
Achwan
Nasrul
N
Zubir
Arnelis
Benyamin
B
Lukito
Irawan
I
Yusuf
Laurentius Adrianus
LA
Lesmana
Ali
A
Sulaiman
D000328:Adult; D001483:Base Sequence; D018387:Codon, Initiator; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000032:analysis / Q000302:isolation & purification; D018450:Disease Progression; D005260:Female; D005819:Genetic Markers; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D007214:Indonesia; D008107:Liver Diseases / Q000821:virology*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D011498:Protein Precursors / Q000235:genetics*; D012307:Risk Factors; D017422:Sequence Analysis, DNA
D018387:Codon, Initiator; D004279:DNA, Viral; D005819:Genetic Markers; D006514:Hepatitis B Surface Antigens; D011498:Protein Precursors; C050807:presurface protein 2, hepatitis B surface antigen