Prevalence of Occult Hepatitis B Virus Infection（OBI） in Subjects With Chronic Hepatitis B（CHB） Family History

Sponsor

First Affiliated Hospital Xi'an Jiaotong University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04672915

Collaborator

(none)

2,000

Enrollment

Location

24.3

Anticipated Duration (Months)

82.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Mother to Child transmission is the main route of hepatitis B virus (HBV) transmission in China, attributing to over 50% HBV infection. Familial aggregation in HBV infection is well recognized with underlying stipulations like mother-to-child transmission（MTCT）, susceptible genes, close contact and other factors. Not surprisingly, a large proportion of hepatitis B virus infected population in China have a family history of hepatitis B virus infection. In clinical practice those family members usually undergo merely hepatitis B virus serology tests without HBV DNA test, which ruled out false HBsAg (-) or Occult HBV Infection (OBI) from Screening and linkage to care (SLTC). Unfortunately, the missed-out OBI in CHB family members was of a greater prevalence compared to those from general population (8.0% vs. 2.6%) . Moreover, OBI has been well recognized as strong risk factor in hepatocellular carcinoma （HCC） development with significant HBV DNA integration into host genome . In light of the latest 2019 China CHB guidelines, treatment criteria covered subjects with family history of CHB related cirrhosis or hepatocellular carcinoma(HCC). Therefore, subjects of HBsAg (+) with normal alanine aminotransferase（ALT） or OBI are eligible for further consideration of HBV anti-viral treatment.

This study proposed will explore the prevalence of OBI in subjects with family history of HBV related cirrhosis or HCC. The screened HBsAg (+) with normal alanine aminotransferase(ALT) and OBI subjects would be linked to anti-viral therapies.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis b	Diagnostic Test: test of HBV DNA

Detailed Description

Serum samples were tested for liver enzymes and liver synthesis function including ALT, aspartate aminotransferase（AST）, and albumin, etc. using a Hitachi 7600 automatic analyzer and reagent system (Hitachi, Tokyo, japan). HBsAg quantification was performed using automated electrochemiluminescence Immunoassay (ECLIA) manufactured by Roche. HBsAb, HBeAg, HBeAb and HBcAb were measured semi-quantitatively using Chemiluminescence Immunoassay (CLIA) manufactured by Abbott Diagnostics (USA). Serum HBV DNA levels were measured using the COBAS TaqMan HBV Monitor Test, with a lower limit of detection of 20 IU/mL (100 copies/mL).

The false negative result excluding OBI due to Real time PCR (lower limit of 20 IU/ml) technically may exist. The study group plan to carry out nested PCR (specifically target the HBV Pre-S, S, Pre-C/Core, and X open reading frames) on subjects with HBsAg (-) HBV DNA (-) and HBcAb(+) to double check the potential false negative result in HBV DNA from Real time PCR. Quantitation of intrahepatic HBV cccDNA by quantitative real-time PCR (qPCR).

Study Design

Study Type:

Observational

Anticipated Enrollment :

2000 participants

Observational Model:

Family-Based

Time Perspective:

Prospective

Official Title:

Prevalence of Occult Hepatitis B Virus Infection（OBI） in Subjects With Chronic Hepatitis B (CHB） Family History and Cascading of Care Linked to Treatment in West China

Actual Study Start Date :

Dec 21, 2020

Anticipated Primary Completion Date :

Nov 15, 2022

Anticipated Study Completion Date :

Dec 30, 2022

Outcome Measures

Primary Outcome Measures

Prevalence of OBI in subjects with CHB family history [1 year]
Serum samples were tested for liver enzymes and liver synthesis function including ALT, Aspartate aminotransferase（AST）, and albumin, etc. using a Hitachi 7600 automatic analyzer.HBsAg quantification was performed using automated electrochemiluminescence Immunoassay (ECLIA) manufactured by Roche, with limit of detection at 0.05 IU/mL or confirmed by the HBsAg confirmatory assay ,with limit of detection at 0.005 IU/mL. HBsAb, HBeAg, HBeAb and HBcAb were measured semi-quantitatively using Chemiluminescence Immunoassay (CLIA) manufactured by Abbott Diagnostics (USA). Serum HBV DNA levels were measured using the COBAS TaqMan HBV Monitor Test, with a lower limit of detection of 20 IU/mL (100 copies/mL).

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

First- and second-degree relatives of CHB patients in west China；
Subjects with family history of CHB related cirrhosis or HCC;
Subjects with ability to understand and sign a written informed consent form.

Exclusion Criteria:

Positive antibody against hepatitis C virus(HCV),hepatitis D Virus(HDV), or human immunodeficiency virus(HIV) (anti-HCV, anti-HDV, or anti-HIV)
Evidence of other autoimmune or metabolic liver diseases (except non-alcoholic fatty liver disease).
Moribund state including advanced/pre-terminal liver cancer or other non-hepatic cancers
Non-hepatic cancer undergoing chemotherapy within last 6 months