Clinical trial NCT04672915: Prevalence of Occult Hepatitis B Virus Infection（OBI） in Subjects With Chronic Hepatitis B（CHB） Family History
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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Chronic Hepatitis b
Lead sponsor: First Affiliated Hospital Xi'an Jiaotong University
Sponsor class: OTHER
First posted: 2020-12-17
Enrollment: 2000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: FAMILY_BASED
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Study population from the family with the history of CHB related cirrhosis or HCC.

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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: Prevalence of OBI in subjects with CHB family history
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Xi'an
country: China
facility: First Affiliated Hospital of Xi'an JiaotongUniversity
state: Shaanxi
Study officials:
affiliation: First Affiliated Hospital of Xian JiaotongUniversity
name: Yingren Zhao
role: STUDY_DIRECTOR
References: