Abstract | AIM: 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. CONCLUSION: 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.
|
Authors | Andi Utama, Marlinang Diarta Siburian, Ismail Fanany, Mariana Destila Bayu Intan, Rama Dhenni, Tri Shinta Kurniasih, Syafruddin A R Lelosutan, Wenny Astuti Achwan, Nasrul Zubir, Arnelis, Benyamin Lukito, Irawan Yusuf, Laurentius Adrianus Lesmana, Ali Sulaiman |
Journal | World journal of gastroenterology
(World J Gastroenterol)
Vol. 18
Issue 38
Pg. 5418-26
(Oct 14 2012)
ISSN: 2219-2840 [Electronic] United States |
PMID | 23082059
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Codon, Initiator
- DNA, Viral
- Genetic Markers
- Hepatitis B Surface Antigens
- Protein Precursors
- presurface protein 2, hepatitis B surface antigen
|
Topics |
- Adult
- Base Sequence
- Codon, Initiator
- Cross-Sectional Studies
- DNA, Viral
(analysis, isolation & purification)
- Disease Progression
- Female
- Genetic Markers
- Hepatitis B Surface Antigens
(genetics)
- Hepatitis B virus
(genetics)
- Humans
- Indonesia
- Liver Diseases
(virology)
- Logistic Models
- Male
- Middle Aged
- Molecular Sequence Data
- Mutation
- Protein Precursors
(genetics)
- Risk Factors
- Sequence Analysis, DNA
|