Know Cancer

or
forgot password

Human Genes Involved in Susceptibility or Resistance to Hepatitis B Virus


N/A
8 Years
N/A
Not Enrolling
Both
Hepatitis B

Thank you

Trial Information

Human Genes Involved in Susceptibility or Resistance to Hepatitis B Virus


Persistent hepatitis B viral (HBV) infection is a significant public health problem because
of the occurence of chronic liver disease, cirrhosis, and hepatocarcinoma (HCC) [1-3].
Roughly one-third of the world population has been infected with HBV and there are about 350
million (5-6%) persistent carriers. HBV causes 80% of all liver cancer and is the second
most important carcinogen, after smoking tobacco. There is an approximate 90% risk of
becoming a persistent carrier following perinatal infection in infants born to e antigen
positive carrier mothers and 30% risk in pre-school children. Only 5-10% of adults become
persistent carriers following infection. Like HIV, HBV is transmitted by contaminated blood
through transfusion or intravenous drug use and by high-risk sexual behavior.

The purpose of this investigation is to study how different outcomes of hepatitis B exposure
and infection are affected by host genetic factors in the Chinese population, where more
than 120 million individuals are infected with HBV. Of people persistently infected with
HBV, 10-30% will develop liver cirrhosis (LC) and hepatocellular carcinoma (HCC). These
highly variable outcomes in both clearance rates and disease outcomes in persistently
infected individuals cannot be fully explained by differences in viral or environmental
factors. Thus, differences in host genetic factors may affect hepatitis B natural history.

Blood will be collected from volunteers in China. Healthy donors unexposed to HBV or HCV,
individuals who have cleared HBV, and asymptomatic carriers of HBV will be identified by the
Peking University hospitals and blood bank. HBV infected individuals with chronic
hepatitis, cirrhosis or HCC will be identified by the Peking University hospital hepatitis
clinics. Targeted individuals will be asked to participate by letter or a telephone
interview by trained hospital staff. A database of clinical and family information will be
created from a questionnaire completed by hospital staff. A database of clinical and family
information will be created from a questionnaire completed by hospital staff interviewers.
Blood will be separated into plasma and peripheral blood mononuclear cells (PBMCs) and
cryopreserved in China. Serum will be tested in China for hepatitis viral markers, HBV
genotypes, and HBV viral load. Two vials of PBMC will be transferred to the LGD, NCI-USA,
for mRNA expression assays and host genetic analysis. Lymphoblastoid cell lines will be
established by the LGD-NCI as a source of renewable DNA. RNA will be extracted from PBMCs
for determination of mRNA expression by the microarray method. Results of mRNA expression
assays and literature searches will be used to identify candidate genes. DNA extracted from
cell lines will be genotyped for single nucleotide polymorphisms (SNPs) in candidate genes
and DNA markers, including HLA, cytokines, chomokines, and their receptors, and putative HBV
cell entry targets by DNA genotyping methods. SNPs in candidate genes will be identified
using public and private SNP databases and SNP discovery methods. SNPs will be genotyped
study participants and analyzed to detect associations between polymorphisms and phenotypes
obtained from clinical and laboratory testing. If a genetic marker associated with the
development of a disease phenotype is found, there are potential applications in diagnostics
and therapy. The identification of allelic polymorphisms in genes involved in the pathway
from chronic viral infection to LC and ultimately HCC would provide insight into the
carcinogenic process.

Inclusion Criteria


- INCLUSION CRITERIA:

A Group - HBV Clearance:

1. HBsAg negative and anti-HBs and anti-HBc positive or anti-HBs positive and no HB
Vaccination history.

2. No systemic diseases.

B Group - Asymptomatic persistent infection:

1. HBsAg, anti-HBc positive for at least 6 months.

2. At least one parent or sibling HBsAG positive .

3. ALT and AST have been in normal range (less than 45 IU/L) at least 5 years

4. No clinical symptoms of hepatitis.

5. No clinical liver cirrhosis.

C Group - Chronic Hepatitis B:

1. HBsAg, anti-HBc positive for more than 6 months.

2. At least one parent or sibling HBsAg positive.

3. ALT and/or AST were greater than or equal to 60 IU/L or greater than 2 times upper
limit of normal.

4. No clinical liver cirrhosis.

5. No other systemic diseases.

D Group - Decompensated liver cirrhosis:

1. HBsAg and anti-HBc positive.

2. At least one parent or sibling HbsAg positive.

3. Decompensated liver cirrhosis (gastroesophageal varication, ascites or edema)

E Group - Primary hepatocellular carcinoma:

1. HbsAg or anti-HBc positive.

2. At least one parent or sibling HBsAg positive.

3. HCC confirmed by liver biopsy or by both AFP an ultrasound, CT or MRI.

F Group - Normal Donor Group:

1. HbsAg negative and anti-HBc and anti-HBs negative

2. ALT and AST are in normal range (less than 45 IU/L)

3. No systemic diseases.

Offspring of cases (for haplotype determinations):

1. Natural child of cases.

2. Age 8 or older.

EXCLUSION CRITERIA:

B thru E Groups:

1. Persons born in 1963 or later.

2. Persons not of Han ethnicity.

3. Persons with no first-order relative (parent or sibling) with HBV infection.

4. Persons who resided in Fusui County of Guangzi Zhuang Autonomous Region or in the
Qidong district of Jiangsu Province for at least 6 months prior to 1986.

5. anti-HCV, HCV RNA, anti-HDV, and/or HDAg.

6. Current infection with HAV or HEV (indicated by antibodies and abnormal liver
function).

7. Persons meeting the inclusion criteria but who are unwilling or unable to give
informed consent.

A & F Groups - HBV Clearance & Normal Donors:

1. Persons born in 1963 or later.

2. Persons not of Han ethnicity.

3. Persons who resided in Fusui County of Guangxi Zhuang Autonomous Region or in the
Qidong district of Jiangsu Province for at least 6 months prior to 1986.

4. Anti-HCV, HCV RNA, anti-HDV and/or HGAg positive.

5. Current infection with HAV or HEV (indicated by antibodies and abnormal liver
function).

6. Persons meeting the inclusion criteria but who are unwilling or unable to give
informed consent.

Type of Study:

Observational

Study Design:

N/A

Principal Investigator

Michael Dean, Ph.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)

Authority:

United States: Federal Government

Study ID:

999902323

NCT ID:

NCT00342186

Start Date:

September 2002

Completion Date:

Related Keywords:

  • Hepatitis B
  • Han Chinese
  • Genotyping
  • Predisposition
  • Hepato Cellular Carcinoma
  • Host-Virus Interaction
  • Hepatitis B
  • HBV
  • Disease Susceptibility
  • Hepatitis
  • Hepatitis A
  • Hepatitis B

Name

Location

National Cancer Institute (NCI), 9000 Rockville PikeBethesda, Maryland  20892