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

Fatou Traoré,Emmanuelle Gormally,Guy Vernet,Marlin D Friesen,Moussa Y Maiga,Stéphanie Villar,Souleymane Diallo,Pierre Hainaut,John D Groopman

doi:10.1186/s12879-015-0916-x

Abstract

BackgroundHepatitis B (HB) infection is common in Mali. However, there is little information on molecular and biochemical characteristics of HB carriers.MethodsA 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.ResultsOverall, 276 subjects were HBsAg-positive (18.8%). Among 152 subjects tested for HBV load, 49 (32.2%) had over 104 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).ConclusionChronic 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.

Highlights

Hepatitis B (HB) infection is common in Mali
We have studied a group of volunteers recruited from various groups of the population in the district of Bamako, Mali, for HB carriage and we have further characterized several molecular, serological and biochemical parameters in the sub-set of those who were confirmed HB carriers
The results show that the rate of HB chronic carriage is high in this study population (18.8%), and that at least 1/ 3 of the carriers have significant signs of liver fibrosis or active hepatitis

Summary

Introduction

Hepatitis B (HB) infection is common in Mali. there is little information on molecular and biochemical characteristics of HB carriers. Chronic carriage of Hepatitis B Virus (HBV) reaches endemic levels (≥8% of the general populations) in many parts of Sub-Saharan Africa, South East Asia and Latin America. HB chronic infection is the main attributable risk factor worldwide for severe chronic liver disease and, significantly, hepatocellular carcinoma (HCC) [1,2]. In West Africa, where rates of chronic HB carriage in the general, non-vaccinated populations are 10-18%, HCC is the leading cancer in males (standardized incidence rates (ASRW) of 15-30/105 person years) and the third in females (ASRW of 7-15/105 person years) [3]. Most HCC patients are aged 35–50 and present with advanced tumors with an average time since first symptoms of only 2–3 months. Very few patients are diagnosed with cirrhosis before HCC detection. A clinical study in The Gambia has shown that, at HCC diagnosis, ultrasonography reveals concomitant cirrhosis in about 65% of the cases, corresponding in many cases to reactive, rather than precursor cirrhosis [4]

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