Hepatitis B virus genotypes and pre- orecore promoter mutations in Palestinian patients with chronic HBV and liver complications

Other Title(s)

تحديد النماط الجينية و التغيرات الوراثية في الجين ما قبل الرئيس و موقع التحكم في الجين الرئيس في فيروس التهاب الكبد الوبائي )‎ب( في المرضى الفلسطينيين المصابين بالتهاب الكبد الوبائي(ب)‎ المزمن و مضاعفات المرض على الكبد

Dissertant

Said, Sawsan Sidqi

Thesis advisor

Surur, Mahmud Abd al-Rahman

Comitee Members

Ramlawi, Asad
Farraj, Muhammad A.

University

Birzeit University

Faculty

Faculty of Science

Department

Department Nutrition and Dietetics

University Country

Palestine (West Bank)

Degree

Master

Degree Date

2008

English Abstract

There are eight genotypes (A-H) of hepatitis B virus (HBV).

The HBV genotypes show distinct geographic distribution and have been shown to influence the clinical course of infection.

Genetic mutations in the Pre-core C (PC) and basal Core Promoter (BCP) may predict the development of hepatocellular carcinoma. In this study, we have genotyped 150 HBV clinical isolates from West Bank region, Palestine.

Patients were categorized into three groups, (i) chronic active hepatitis (n=118), (ii) liver cirrhosis (n=27) and (iii) hepatocellular carcinoma (n=5).

Genotyping was performed by multiplex nested-PCR using genotype-specific primers complementary to pre-S1/S gene for A-F genotypes.

While genotype G was genotyped by nested PCR using primers specific for a 36_bp insertion in the core gene. Genotyping was verified by DNA sequencing and phylogenetic analysis.

PCR-RFLP analysis was used to investigate PC / BCP mutations. The most prevalent genotypes were genotype D (25.3 %) and A (4.7 %) in the West Bank region/Palestine.

Remarkably a high prevalence of mixed HBV genotypesinfections mainly due to A+D (35.3 %) were observed.

Genotypes B and C were observed only as part of a mixed infection but not as a single genotype.

Infection with mixed genotypes was more predominant among patients with liver cirrhosis (19/27) xiv than patients without cirrhosis (77/123).

The prevalence of negative HBeAg (68 %) was higher than positive HBeAg among our study population.

However, mixed genotypes particularly A+D (71.1 %), tend to predominate among negative HBeAg patients compared to positive HBeAg patients. Concerning the BCP mutation and precore region/ codon 15 variants, the BCP mutation was the predominant mutation among HBV isolates analysed in this study.

A statistically significant correlation was observed between the HBV genotypes and BCP mutation (p<0.03).

Analysis of the correlation between the HBV genotypes and PC mutation (p<0.16) and codon 15 variants (p<0.16), showed no significant correlation (p<0.16).

But PC mutation tends to occur more predominantly among cirrhosis patients than CAH patients. This study showed that genotype D as the most prevalent one, and a markedly high prevalence of mixed A+D genotypes’ infections among Palestinian patients with chronic HBV.

These findings indicate that mixed genotypes’ infection is associated with a higher risk for development of liver complications or bad clinical outcome (bad prognosis).

The PC mutation is a positive predictive marker for liver cirrhosis and the presence of BCP mutation (G1896A) is a negative predictor for HCC.

Main Subjects

Biology
Medicine

Topics

• Liver
• Genetics
• Diseases
• Palestine

No. of Pages

78

Table of Contents

• APA
• MLA
• AMA

Language

English

Data Type

Arab Theses

Record ID

BIM-303662