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Molecular characteristics of Hepatitis B and chronic liver disease in a cohort of HB carriers from Bamako, Mali.

Traoré F, Gormally E, Villar S, Friesen MD, Groopman JD, Vernet G, Diallo S, Hainaut P, Maiga MY - BMC Infect. Dis. (2015)

Bottom Line: Among 105 subjects tested, 60% had detectable levels of R249S copies (>40 copies/mL plasma).Chronic HB carriage in adults in Bamako district is well over epidemic threshold.These results support introduction of anti-HB therapies to reduce the progression towards severe liver disease.

View Article: PubMed Central - PubMed

Affiliation: Centre d'Infectiologie Charles Mérieux, Bamako, République du Mali. fatimtraorefaye@hotmail.fr.

ABSTRACT

Background: Hepatitis B (HB) infection is common in Mali. However, there is little information on molecular and biochemical characteristics of HB carriers.

Methods: A group of 1466 adult volunteers was recruited in the district of Bamako. Confirmed HB carriers were tested for HB viral load by quantitative PCR and HBV was genotyped by sequencing of HBS. Fibrosis and hepatitis activity were measured using the Fibrotest-Actitest. A mutation of TP53 at codon 249 (R249S), specific for exposure to aflatoxin, was detected in cell-free DNA extracted from plasma.

Results: Overall, 276 subjects were HBsAg-positive (18.8%). Among 152 subjects tested for HBV load, 49 (32.2%) had over 10(4) copies/mL and 16 (10.5%) had levels below the limit of detection. The E genotype was found in 91.1% of carriers. Fibrotest scores ≥ F2 were observed in 52 subjects (35.4%). Actitest scores ≥ A2 were detected in 15 subjects (10.2%) and were correlated with Fibrotest scores (p = 0.0006). Among 105 subjects tested, 60% had detectable levels of R249S copies (>40 copies/mL plasma).

Conclusion: Chronic HB carriage in adults in Bamako district is well over epidemic threshold. About 1/3 of carriers have moderate to severe liver fibrosis and 60% have detectable aflatoxin-related TP53 R249S mutation. These results support introduction of anti-HB therapies to reduce the progression towards severe liver disease.

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Related in: MedlinePlus

Flow chart of subject recruitment and selection for analysis. 1466 subjects were initially recruited. Due to practical reasons in a resource-constrained context (in which extensive and systematic follow-up of healthy subjects is not feasible), studies on biomarkers have been carried out on second or third blood samples collected at recall of subjects who were confirmed chronic carriers. From the initial recruitment, a total of 199 subjects reported for the first recall and carrier status was confirmed for 195 subjects. Among these subjects, 152 reported for a third sample, which was used to measure viral load (152 subjects) and to perform Actitest/Fibrotest (147 subjects; data on 5 subjects not available due to experimental failure). Among these 147 subjects, DNA could be extracted from the plasma for 105 subjects, who were tested for R249S, HBX (n = 105), HBe testing (n = 103) or HBV genotype (n = 90). The reduction in numbers for HBe and HBV genotype is due to experimental failure.
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Fig1: Flow chart of subject recruitment and selection for analysis. 1466 subjects were initially recruited. Due to practical reasons in a resource-constrained context (in which extensive and systematic follow-up of healthy subjects is not feasible), studies on biomarkers have been carried out on second or third blood samples collected at recall of subjects who were confirmed chronic carriers. From the initial recruitment, a total of 199 subjects reported for the first recall and carrier status was confirmed for 195 subjects. Among these subjects, 152 reported for a third sample, which was used to measure viral load (152 subjects) and to perform Actitest/Fibrotest (147 subjects; data on 5 subjects not available due to experimental failure). Among these 147 subjects, DNA could be extracted from the plasma for 105 subjects, who were tested for R249S, HBX (n = 105), HBe testing (n = 103) or HBV genotype (n = 90). The reduction in numbers for HBe and HBV genotype is due to experimental failure.

Mentions: A total of 1466 adult volunteers were recruited between March and September 2009. These volunteers were contacted through on-site information among different groups, including students (Faculty of Medicine and Pharmacy and National School for Police, Bamako), university hospital staff and visitors (Kati hospital; Point G and Gabriel Touré hospitals in Bamako) (Figure 1). None of the subjects recruited had been referred to this study on the basis of prevalent hepatic symptoms and none had been previously tested for HB status. At the start of the study, a blood sample (4 mL) was obtained by venipuncture using standard vacutainers. Blood samples were processed immediately for initial serological tests. A second sample was obtained at least 6 months after the initial sample. This second sample was used for confirming the HB carrier status. Confirmed carriers were requested to complete a questionnaire with basic demographic information, history of liver disease and hepatitis. A third sample was obtained from 152 subjects and was used for biochemical and molecular tests. Molecular analyses were performed using blood products (plasma) stored at −80°C. Prior to inclusion into the study, subjects received individual information by a medical doctor of the Hepato-Gastroenterology department, Hospital Gabriel Touré and oral informed consent was obtained. The study protocol was approved by the ethical committee of INRSP (Institut National de Recherche en Santé Publique, decision N°09-000008/CE-INRSP, 19th of May 2009), according to national regulations in Mali.Figure 1


Molecular characteristics of Hepatitis B and chronic liver disease in a cohort of HB carriers from Bamako, Mali.

Traoré F, Gormally E, Villar S, Friesen MD, Groopman JD, Vernet G, Diallo S, Hainaut P, Maiga MY - BMC Infect. Dis. (2015)

Flow chart of subject recruitment and selection for analysis. 1466 subjects were initially recruited. Due to practical reasons in a resource-constrained context (in which extensive and systematic follow-up of healthy subjects is not feasible), studies on biomarkers have been carried out on second or third blood samples collected at recall of subjects who were confirmed chronic carriers. From the initial recruitment, a total of 199 subjects reported for the first recall and carrier status was confirmed for 195 subjects. Among these subjects, 152 reported for a third sample, which was used to measure viral load (152 subjects) and to perform Actitest/Fibrotest (147 subjects; data on 5 subjects not available due to experimental failure). Among these 147 subjects, DNA could be extracted from the plasma for 105 subjects, who were tested for R249S, HBX (n = 105), HBe testing (n = 103) or HBV genotype (n = 90). The reduction in numbers for HBe and HBV genotype is due to experimental failure.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4403772&req=5

Fig1: Flow chart of subject recruitment and selection for analysis. 1466 subjects were initially recruited. Due to practical reasons in a resource-constrained context (in which extensive and systematic follow-up of healthy subjects is not feasible), studies on biomarkers have been carried out on second or third blood samples collected at recall of subjects who were confirmed chronic carriers. From the initial recruitment, a total of 199 subjects reported for the first recall and carrier status was confirmed for 195 subjects. Among these subjects, 152 reported for a third sample, which was used to measure viral load (152 subjects) and to perform Actitest/Fibrotest (147 subjects; data on 5 subjects not available due to experimental failure). Among these 147 subjects, DNA could be extracted from the plasma for 105 subjects, who were tested for R249S, HBX (n = 105), HBe testing (n = 103) or HBV genotype (n = 90). The reduction in numbers for HBe and HBV genotype is due to experimental failure.
Mentions: A total of 1466 adult volunteers were recruited between March and September 2009. These volunteers were contacted through on-site information among different groups, including students (Faculty of Medicine and Pharmacy and National School for Police, Bamako), university hospital staff and visitors (Kati hospital; Point G and Gabriel Touré hospitals in Bamako) (Figure 1). None of the subjects recruited had been referred to this study on the basis of prevalent hepatic symptoms and none had been previously tested for HB status. At the start of the study, a blood sample (4 mL) was obtained by venipuncture using standard vacutainers. Blood samples were processed immediately for initial serological tests. A second sample was obtained at least 6 months after the initial sample. This second sample was used for confirming the HB carrier status. Confirmed carriers were requested to complete a questionnaire with basic demographic information, history of liver disease and hepatitis. A third sample was obtained from 152 subjects and was used for biochemical and molecular tests. Molecular analyses were performed using blood products (plasma) stored at −80°C. Prior to inclusion into the study, subjects received individual information by a medical doctor of the Hepato-Gastroenterology department, Hospital Gabriel Touré and oral informed consent was obtained. The study protocol was approved by the ethical committee of INRSP (Institut National de Recherche en Santé Publique, decision N°09-000008/CE-INRSP, 19th of May 2009), according to national regulations in Mali.Figure 1

Bottom Line: Among 105 subjects tested, 60% had detectable levels of R249S copies (>40 copies/mL plasma).Chronic HB carriage in adults in Bamako district is well over epidemic threshold.These results support introduction of anti-HB therapies to reduce the progression towards severe liver disease.

View Article: PubMed Central - PubMed

Affiliation: Centre d'Infectiologie Charles Mérieux, Bamako, République du Mali. fatimtraorefaye@hotmail.fr.

ABSTRACT

Background: Hepatitis B (HB) infection is common in Mali. However, there is little information on molecular and biochemical characteristics of HB carriers.

Methods: A group of 1466 adult volunteers was recruited in the district of Bamako. Confirmed HB carriers were tested for HB viral load by quantitative PCR and HBV was genotyped by sequencing of HBS. Fibrosis and hepatitis activity were measured using the Fibrotest-Actitest. A mutation of TP53 at codon 249 (R249S), specific for exposure to aflatoxin, was detected in cell-free DNA extracted from plasma.

Results: Overall, 276 subjects were HBsAg-positive (18.8%). Among 152 subjects tested for HBV load, 49 (32.2%) had over 10(4) copies/mL and 16 (10.5%) had levels below the limit of detection. The E genotype was found in 91.1% of carriers. Fibrotest scores ≥ F2 were observed in 52 subjects (35.4%). Actitest scores ≥ A2 were detected in 15 subjects (10.2%) and were correlated with Fibrotest scores (p = 0.0006). Among 105 subjects tested, 60% had detectable levels of R249S copies (>40 copies/mL plasma).

Conclusion: Chronic HB carriage in adults in Bamako district is well over epidemic threshold. About 1/3 of carriers have moderate to severe liver fibrosis and 60% have detectable aflatoxin-related TP53 R249S mutation. These results support introduction of anti-HB therapies to reduce the progression towards severe liver disease.

Show MeSH
Related in: MedlinePlus