Hepatitis B, ChronicNCT04886102
Molecular Epidemiology of Hepatitis B in Cayenne General Hospital, French Guiana
An observational study of Hepatitis B, Chronic and Adults, run by Centre Hospitalier de Cayenne at 1 site in French Guiana.
Trial summary
In South America, the prevalence of HBV is variable but high (> 8%) in the Amazon basin. In some areas, a third of HBsAg carriers are also infected with HDV, a major comorbidity factor. The pre-core mutations are associated with the negative HBe Ag phenotype which is associated with a more severe course. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatitis B, Chronic, Adults
- What is being tested?
- An additional 5 mL venous blood tube taken from patients during their routine medical check-up at the hospital
- How many people
- 400 participants
- Where
- 1 siteFrench Guiana
- Study dates
- 11 Feb 2021to 1 Feb 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adult patients infected with hepatitis B followed at the Cayenne hospital center (adult day hospital consultations, consultations with the infectious and tropical diseases department and hepatology B medicine consultations) Estimated size of target population: 1000
Who may be able to join
- Age ≥ 18 years old
- Person with confirmed chronic hepatitis B
- Person who does not object to their participation in the protocol
- HBV viral load> = 500 copies / mL
- Person who has planned / is willing to have their next HBV assessment of current care taken at the Cayenne Hospital center
Who cannot join
- Refusal to participate
- Age <18 years old
- Person opposing their participation in the protocol
- HBV viral load <500 copies / mL
- Person who has not planned / been unwilling to have their next HBV assessment of current care taken at the Cayenne Hospital center
Trial locations and contacts
1 site in 1 country.
French Guiana1 site, 1 recruiting
- Recruiting
General Hospital of Cayenne
Cayenne, 97306
Mathieu Nacher, MD, PhD, +594 594 39 50 24 ext. 5024, mathieu.nacher@ch-cayenne.fr
About this study
In South America, the prevalence of HBV is variable but high (> 8%) in the Amazon basin. In some areas, a third of HBsAg carriers are also infected with HDV, a major comorbidity factor. The pre-core mutations are associated with the negative HBe Ag phenotype which is associated with a more severe course. These mutations are of increasing and high frequency. French Guiana is populated by populations of African, European and Asian origins with chains of viral transmission which are not known and viruses probably of different origins with variable virulence and transmission potentials.
Read the detailed description
Human demography and migrations play a crucial role in the phylogeography of viral populations. Hepatitis B viruses are characterized by a high genetic diversity which results from the fact that this virus uses a reverse transcriptase during its replicative cycle, which induces errors and therefore variation. A dozen genotypes have so far been described and are subdivided into sub-genotypes which have a distinct ethnogeographic distribution. Genotypes A and D are ubiquitous and represent the most common genotypes in Europe; genotypes B and C are very common in Asia and Oceania, genotype E in Central Africa and West Africa, genotypes H and F in Latin America and Alaska, and Genotype I in Southeast Asia. The populations originating from these different continents are all represented in Guyana and it is therefore interesting to understand what are the chains of transmission and the phylodynamic aspects of the epidemic in French Guiana. In addition, the different genotypes have variable clinical consequences, and this in different ways depending on the ethnicity of the host. Thus, in Mexico, the F and H genotypes appear to be rather benign in the Amerindians among whom they have circulated for a long time. On the other hand, genotypes F, A and D are of rather severe evolution in Mexicans of Caucasian origin, thus suggesting that the immunogenetic factors of the host are important determinants of the pathogenic power of the viruses (Roman and al WJG 2014).
Some pre-core mutations leave the virus with the capacity to replicate. The absence of the HBe antigen deprives the immune system of an important target and the virus can therefore continue to replicate. These pre-core mutations are associated with the HBe Ag negative phenotype (7 to 30% of patients) which is associated with a more severe course of chronic hepatitis. These mutations are of increasing and high frequency (Funk ML, and al 2001).
Addiction to crack cocaine is widespread in French Guiana and appears to be one of the drivers of the epidemic. The pipes used to smoke crack cause burns on the lips and when sharing the pipe could contribute to increasing the risk of transmission (Fischer and al 2008). Risky sexual behavior is associated with the use of crack cocaine, suggesting that there may be specific chains of transmission around crack users.
Primary objective Identify the factors associated with different genotypes (age, sex, country of birth, sexual orientation, sexual risk taking, notion of IV drug addiction, crack ...) in order to identify specific chains of transmission in French Guiana.
Secondary objectives
- Describe the molecular epidemiology of hepatitis B (AgS and pre-core mutations) in French Guiana
- Carry out the phylodynamic study of the different HBV genotypes in order to reconstruct the history of the epidemic in French Guiana
- Identify the clinical prognostic factors associated with the different genotypes and phylogenetic aspects in order to identify the viruses with the greatest pathogenic potential in French Guiana
- Describe the molecular epidemiology of hepatitis D in B-D coinfected in French Guiana
Cross-sectional, monocentric, observational study with biological collection.
Research protocol involving the human person (Category 3 - Non-interventional research_ not related to a health product)
- Conditions
- Hepatitis B, Chronic, Adults
- Being tested
- An additional 5 mL venous blood tube taken from patients during their routine medical check-up at the hospital
- Keywords
- Hepatitis B, Chronic, Hepatitis B Virus Infection, Adults, French Guiana, Hepatitis C Virus Infection, Co-infection, Chain of transmission, Epidemiology, molecular, Viral phylodynamics, Viral phylogenetics
- Medical subject headings
- Hepatitis B, Chronic, Hepatitis B, Hepatitis C, Coinfection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
An additional 5 mL venous blood tube taken from patients during their routine medical check-up at the hospitalOther
Also called Molecular biology analyzes of hepatitis B and D, Phylogenetic and phylodynamic analyzes of hepatitis B, Phylogenetic and phylodynamic analyzes of hepatitis C
Research protocol involving the human person (Category 3 - Non-interventional research_ not related to a health product) Serology, molecular biology, phylogenetic and phylodynamic analyzes of hepatitis B and D
What is being measured
The primary outcome is the main question the study is designed to answer.
Hepatitis B virus (HBV) sequencing
The mutations studied will be those relating to AgS and to the pre-core regions.
The viral nucleic acids will be extracted using the Qiagen® technique on the Qiacube® machine. The HBV genotyping will be carried out by sequencing the nucleotides of a DNA segment amplified from the HBV S gene (nt 414 to nt 822, reference sequence HBV strain NC003977). In order to study the genetic proximity between the HBV strains, the samples will be subjected to whole genome sequencing based on the method of Ramachandran et al using two amplification steps. The first round of whole genome amplification will be followed by a second round of PCR nested on 6 overlapping fragments of 600bp each.
A phylodynamic approach will estimate the aspects time of viral evolution. Phylogenetic trees will be produced to illustrate the genetic differences between the different types of viruses circulating in French Guiana with Mega software.
Measured: 2 years
Secondary outcomes (2)
Hepatitis D virus (VHD) sequencing
In patients also with HDV infection, HDV genotyping will be performed by nucleotide sequencing and phylogenetic analysis of the amplified R0 regions of the genome (nt 889 to nt 1289). The complete sequences will be characterized by the amplification and sequencing of 4 overlapping regions covering the entire genome: R0 (nt 889 to nt 1289), R1 (nt 320 to nt 1289), R2 (nt 889 to nt 420) and R3 (nt 200 to nt 560).
A phylodynamic approach will estimate the aspects time of viral evolution. Phylogenetic trees will be produced to illustrate the genetic differences between the different types of viruses circulating in French Guiana with Mega software.
Measured: 2 years
Liver function Markers
Various liver function markers will be taken. Several groups will be distinguished and compared in terms of genotype and subclades, thus testing the null hypothesis of an absence of difference between genotypes and markers of evolution. Association will be assessed using Chi square tests for crosstabulation of categorical variables and other genotypes (exploratory analyses).
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2021
- Study start11 Feb 2021
- Primary completion1 Feb 2022 (estimated)
- Study completion1 Feb 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatitis B, ChronicStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier de Cayenne
- Sponsor type
- University, hospital or other
- Collaborators
- Hospital Avicenne, University Hospital, Montpellier, Direction Générale de l'Offre de Soins
- Responsible party
- Sponsor
- Investigators
- Mathieu NACHER, MD, PhD, Principal investigator, Centre Hospitalier de Cayenne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04886102
- Sponsor's protocol ID
- EMOHCAY
- Status last verified
- May 2021
- First submitted
- 27 Jan 2021
- Last updated
- 13 May 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Molecular Epidemiology of Hepatitis B in Cayenne General Hospital, French Guiana
- ClinicalTrials.gov ID
- NCT04886102
- Acronym / sponsor ID
- EMOHCAY
- Conditions
- Hepatitis B, Chronic, Adults
- Keywords
- Hepatitis B, Chronic, Hepatitis B Virus Infection, Adults, French Guiana, Hepatitis C Virus Infection, Co-infection, Chain of transmission, Epidemiology, molecular
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- Centre Hospitalier de CayenneUniversity, hospital or other
- Collaborators
- Hospital Avicenne, University Hospital, Montpellier, Direction Générale de l'Offre de Soins
- Study start
- 11 Feb 2021 (actual)
- Primary completion
- 1 Feb 2022 (estimated)
- Study completion
- 1 Feb 2022 (estimated)
- First posted
- 13 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In South America, the prevalence of HBV is variable but high (> 8%) in the Amazon basin. In some areas, a third of HBsAg carriers are also infected with HDV, a major comorbidity factor. The pre-core mutations are associated with the negative HBe Ag phenotype which is associated with a more severe course. These mutations are of increasing and high frequency. French Guiana is populated by populations of African, European and Asian origins with chains of viral transmission which are not known and viruses probably of different origins with variable virulence and transmission potentials.
Detailed description
Human demography and migrations play a crucial role in the phylogeography of viral populations. Hepatitis B viruses are characterized by a high genetic diversity which results from the fact that this virus uses a reverse transcriptase during its replicative cycle, which induces errors and therefore variation. A dozen genotypes have so far been described and are subdivided into sub-genotypes which have a distinct ethnogeographic distribution. Genotypes A and D are ubiquitous and represent the most common genotypes in Europe; genotypes B and C are very common in Asia and Oceania, genotype E in Central Africa and West Africa, genotypes H and F in Latin America and Alaska, and Genotype I in Southeast Asia. The populations originating from these different continents are all represented in Guyana and it is therefore interesting to understand what are the chains of transmission and the phylodynamic aspects of the epidemic in French Guiana. In addition, the different genotypes have variable clinical consequences, and this in different ways depending on the ethnicity of the host. Thus, in Mexico, the F and H genotypes appear to be rather benign in the Amerindians among whom they have circulated for a long time. On the other hand, genotypes F, A and D are of rather severe evolution in Mexicans of Caucasian origin, thus suggesting that the immunogenetic factors of the host are important determinants of the pathogenic power of the viruses (Roman and al WJG 2014).
Some pre-core mutations leave the virus with the capacity to replicate. The absence of the HBe antigen deprives the immune system of an important target and the virus can therefore continue to replicate. These pre-core mutations are associated with the HBe Ag negative phenotype (7 to 30% of patients) which is associated with a more severe course of chronic hepatitis. These mutations are of increasing and high frequency (Funk ML, and al 2001).
Addiction to crack cocaine is widespread in French Guiana and appears to be one of the drivers of the epidemic. The pipes used to smoke crack cause burns on the lips and when sharing the pipe could contribute to increasing the risk of transmission (Fischer and al 2008). Risky sexual behavior is associated with the use of crack cocaine, suggesting that there may be specific chains of transmission around crack users.
Primary objective Identify the factors associated with different genotypes (age, sex, country of birth, sexual orientation, sexual risk taking, notion of IV drug addiction, crack ...) in order to identify specific chains of transmission in French Guiana.
Secondary objectives
- Describe the molecular epidemiology of hepatitis B (AgS and pre-core mutations) in French Guiana
- Carry out the phylodynamic study of the different HBV genotypes in order to reconstruct the history of the epidemic in French Guiana
- Identify the clinical prognostic factors associated with the different genotypes and phylogenetic aspects in order to identify the viruses with the greatest pathogenic potential in French Guiana
- Describe the molecular epidemiology of hepatitis D in B-D coinfected in French Guiana
Cross-sectional, monocentric, observational study with biological collection.
Research protocol involving the human person (Category 3 - Non-interventional research_ not related to a health product)
Study design
- Observational model
- Case only
- Time perspective
- Cross-sectional
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adult patients infected with hepatitis B followed at the Cayenne hospital center (adult day hospital consultations, consultations with the infectious and tropical diseases department and hepatology B medicine consultations) Estimated size of target population: 1000
Key inclusion criteria (5 listed)
- Age ≥ 18 years old
- Person with confirmed chronic hepatitis B
- Person who does not object to their participation in the protocol
- HBV viral load> = 500 copies / mL
- Person who has planned / is willing to have their next HBV assessment of current care taken at the Cayenne Hospital center
Key exclusion criteria (5 listed)
- Refusal to participate
- Age <18 years old
- Person opposing their participation in the protocol
- HBV viral load <500 copies / mL
- Person who has not planned / been unwilling to have their next HBV assessment of current care taken at the Cayenne Hospital center
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| An additional 5 mL venous blood tube taken from patients during their routine medical check-up at the hospitalAlso: Molecular biology analyzes of hepatitis B and D, Phylogenetic and phylodynamic analyzes of hepatitis B, Phylogenetic and phylodynamic analyzes of hepatitis CResearch protocol involving the human person (Category 3 - Non-interventional research_ not related to a health product) Serology, molecular biology, phylogenetic and phylodynamic analyzes of hepatitis B and D | Other | – |
Primary outcome
Hepatitis B virus (HBV) sequencing
Time frame: 2 years
The mutations studied will be those relating to AgS and to the pre-core regions. The viral nucleic acids will be extracted using the Qiagen® technique on the Qiacube® machine. The HBV genotyping will be carried out by sequencing the nucleotides of a DNA segment amplified from the HBV S gene (nt 414 to nt 822, reference sequence HBV strain NC003977). In order to study the genetic proximity between the HBV strains, the samples will be subjected to whole genome sequencing based on the method of Ramachandran et al using two amplification steps. The first round of whole genome amplification will be followed by a second round of PCR nested on 6 overlapping fragments of 600bp each. A phylodynamic approach will estimate the aspects time of viral evolution. Phylogenetic trees will be produced to illustrate the genetic differences between the different types of viruses circulating in French Guiana with Mega software.
2 secondary outcomes
Hepatitis D virus (VHD) sequencing
Time frame: 2 years
Liver function Markers
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mathieu NACHER, MD, PhD principal investigator
Centre Hospitalier de Cayenne
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hepatitis B, Chronic and Adults, run by Centre Hospitalier de Cayenne at 1 site in French Guiana.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 13 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in French Guiana. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Roxane SCHAUB, MD (+594 594 39 55 96, roxane.schaub@ch-cayenne.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hepatitis B virus (HBV) sequencing (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2021.