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

BMC Infectious Diseases

Moussa Y Maiga⁵  Pierre Hainaut¹  Souleymane Diallo³  Guy Vernet⁴  John D Groopman²  Marlin D Friesen²  Stéphanie Villar⁷  Emmanuelle Gormally⁶  Fatou Traoré³ 

[1]International Prevention Research Institute, Lyon, France

[2]Bloomberg School of Public Health, Johns Hopkins University, Baltimore, USA

[3]Centre d’Infectiologie Charles Mérieux, Bamako, République du Mali

[4]Centre Pasteur du Cameroun, Yaoundé, Cameroun

[5]Service de Gastroentérologie et Hépatologie, Centre Hospitalier Universitaire Gabriel Touré, Bamako, République du Mali

[6]Université de Lyon, UMRS 449

[7] Laboratoire de Biologie générale, Université Catholique de Lyon

[8] Reproduction et développement comparé, EPHE, Lyon, France

[9]International Agency for Research on Cancer, Lyon, France

关键词: Mali;    TP53 R249S mutation;    Fibrotest/Actitest;    Chronic carriage;    Viral load;    HBV;   

Others  :  1172446
DOI  :  10.1186/s12879-015-0916-x

 received in 2014-09-24, accepted in 2015-03-27,  发布年份 2015

【 摘 要 】

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 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).

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.

【 授权许可】

   
2015 Traoré et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Plymoth A, Viviani S, Hainaut P: Control of hepatocellular carcinoma through hepatitis B vaccination in areas of high endemicity: perspectives for global liver cancer prevention. Cancer Lett 2009, 286:15-21.
• [2]Pujol FH, Navas M-C, Hainaut P, Chemin I: Worldwide genetic diversity of HBV genotypes and risk of hepatocellular carcinoma. Cancer Lett 2009, 286:80-8.
• [3]Ferlay J, Shin H-R, Bray F, Forman D, Mathers C, Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010, 127:2893-917.
• [4]Umoh NJ, Lesi OA, Mendy M, Bah E, Akano A, Whittle H, et al.: Aetiological differences in demographical, clinical and pathological characteristics of hepatocellular carcinoma in The Gambia. Liver Int 2011, 31:215-21.
• [5]Kirk GD, Bah E, Montesano R: Molecular epidemiology of human liver cancer: insights into etiology, pathogenesis and prevention from The Gambia, West Africa. Carcinogenesis 2006, 27:2070-82.
• [6]Popalis C, Yeung LTF, Ling SC, Ng V, Roberts EA: Chronic hepatitis B virus (HBV) infection in children: 25 years’ experience. J Viral Hepat 2013, 20:e20-6.
• [7]Kirk GD, Lesi OA, Mendy M, Akano AO, Sam O, Goedert JJ, et al.: The Gambia Liver Cancer Study: infection with hepatitis B and C and the risk of hepatocellular carcinoma in West Africa. Hepatology 2004, 39:211-9.
• [8]Szymañska K, Chen J-G, Cui Y, Gong YY, Turner PC, Villar S, et al.: TP53 R249S mutations, exposure to aflatoxin, and occurrence of hepatocellular carcinoma in a cohort of chronic hepatitis B virus carriers from Qidong, China. Cancer Epidemiol Biomarkers Prev 2009, 18:1638-43.
• [9]Villar S, Le Roux-Goglin E, Gouas DA, Plymoth A, Ferro G, Boniol M, et al. Seasonal Variation in TP53 R249S-mutated Serum DNA With Aflatoxin Exposure And Hepatitis B Virus Infection. Environ Health Perspect. 2011. doi:10.1289/ehp.1103539.
• [10]Diarra A, Kouriba B, Baby M, Murphy E, Lefrere J-J: HIV, HCV, HBV and syphilis rate of positive donations among blood donations in Mali: lower rates among volunteer blood donors. Transfus Clin Biol 2009, 16:444-7.
• [11]Diarra M, Konate A, Minta D, Sounko A, Dembele M, Toure CS, et al.: Epidemiologic aspects of human immunodeficiency virus and hepatitis virus infections. Mali Med 2006, 21:27-30.
• [12]Koné MC, Sidibé ET, Mallé KK, Beye SA, Lurton G, Dao S, et al.: Seroprevalence of human immunodeficiency virus, hepatitis B virus and hepatitis C virus among blood donors in Segou, Mali. Med Sante Trop 2012, 22:97-8.
• [13]MacLean B, Hess RF, Bonvillain E, Kamate J, Dao D, Cosimano A, et al.: Seroprevalence of hepatitis B surface antigen among pregnant women attending the Hospital for Women & Children in Koutiala, Mali. S Afr Med J 2012, 102:47-9.
• [14]Maiga YI, Gassin M, Rhaly AA, Pillot J, Marjolet M, Morel D, et al.: Prevalence of hepatitis B virus in women of childbearing age in Mali. Bull Soc Pathol Exot 1990, 83:93-9.
• [15]Maiga YI, Marjolet M, Ag Rhaly A, Pillot J: Transmission of hepatitis B virus from mother to child in Bamako-Mali. Bull Soc Pathol Exot 1992, 85:5-9.
• [16]Sidibe S, Sacko BY, Traoré I: Prevalence of serologic markers of the hepatitis B virus in pregnant women of Bamako, Mali. Bull Soc Pathol Exot 2001, 94:339-41.
• [17]Tounkara A, Sarro YS, Kristensen S, Dao S, Diallo H, Diarra B, et al.: Seroprevalence of HIV/HBV coinfection in Malian blood donors. J Int Assoc Physicians AIDS Care (Chic) 2009, 8:47-51.
• [18]Maiga MY, Dembele M, Maiga I, Sanago B, Sangare D, Traoré HA: Case–control study of hepatitis C HBs Ag and antivirus antibodies in chronic hepatopathies. Sante 2002, 12:389-92.
• [19]Diarra M, Konaté A, Soukho A, Dicko M, Kallé A, Doumbia K, et al.: Changing aspects of cirrhotic disease in a hepato-gastroenterology service in Mali. Mali Med 2010, 25:42-6.
• [20]Ngo Y, Benhamou Y, Thibault V, Ingiliz P, Munteanu M, Lebray P, et al. An Accurate Definition of the Status of Inactive Hepatitis B Virus Carrier by a Combination of Biomarkers (FibroTest-ActiTest) and Viral Load. PLoS One. 2008;3. doi: 10.1371/journal.pone.0002573.
• [21]Poynard T, Morra R, Ingiliz P, Imbert-Bismut F, Thabut D, Messous D, et al.: Biomarkers of liver fibrosis. Adv Clin Chem 2008, 46:131-60.
• [22]Villar S, Le Roux-Goglin E, Gouas DA, Plymoth A, Ferro G, Boniol M, et al.: Seasonal variation in TP53 R249S-mutated serum DNA with aflatoxin exposure and hepatitis B virus infection. Environ Health Perspect 2011, 119:1635-40.
• [23]Lleonart ME, Kirk GD, Villar S, Lesi OA, Dasgupta A, Goedert JJ, et al.: Quantitative analysis of plasma TP53 249Ser-mutated DNA by electrospray ionization mass spectrometry. Cancer Epidemiol Biomarkers Prev 2005, 14:2956-62.
• [24]Ma N-F, Lau SH, Hu L, Xie D, Wu J, Yang J, et al.: COOH-Terminal truncated HBV X protein plays key role in hepatocarcinogenesis. Clin Cancer Res 2008, 14:5061-8.
• [25]Gouas DA, Shi H, Hautefeuille AH, Ortiz-Cuaran SL, Legros PC, Szymanska KJ, et al.: Effects of the TP53 p.R249S mutant on proliferation and clonogenic properties in human hepatocellular carcinoma cell lines: interaction with hepatitis B virus X protein. Carcinogenesis 2010, 31:1475-82.
• [26]Ortiz-Cuaran S, Villar S, Gouas D, Ferro G, Plymoth A, Khuhaprema T, et al.: Association between HBX status, aflatoxin-induced R249S TP53 mutation and risk of hepatocellular carcinoma in a case–control study from Thailand. Cancer Lett 2013, 331:46-51.
• [27]Abedi-Ardekani B, Gouas D, Villar S, Sotoudeh M, Hainaut P: TP53 mutations and HBX status analysis in hepatocellular carcinomas from Iran: evidence for lack of association between HBV genotype D and TP53 R249S mutations. Hepat Res Treat 2011, 2011:1-6.
• [28]Gouas D, Shi H, Hainaut P: The aflatoxin-induced TP53 mutation at codon 249 (R249S): biomarker of exposure, early detection and target for therapy. Cancer Lett 2009, 286:29-37.
• [29]Groopman JD, Kensler TW, Wild CP: Protective interventions to prevent aflatoxin-induced carcinogenesis in developing countries. Annu Rev Public Health 2008, 29:187-203.
• [30]Kuniholm MH, Lesi OA, Mendy M, Akano AO, Sam O, Hall AJ, et al.: Aflatoxin exposure and viral hepatitis in the etiology of liver cirrhosis in the Gambia, West Africa. Environ Health Perspect 2008, 116:1553-7.
• [31]Vray M, Debonne JM, Sire JM, Tran N, Chevalier B, Plantier JC, et al.: Molecular epidemiology of hepatitis B virus in Dakar, Sénégal. J Med Virol 2006, 78:329-34.
• [32]Viviani S, Carrieri P, Bah E, Hall AJ, Kirk GD, Mendy M, et al.: 20 years into the Gambia Hepatitis Intervention Study: assessment of initial hypotheses and prospects for evaluation of protective effectiveness against liver cancer. Cancer Epidemiol Biomarkers Prev 2008, 17:3216-23.
• [33]Olinger CM, Venard V, Njayou M, Oyefolu AOB, Maïga I, Kemp AJ, et al.: Phylogenetic analysis of the precore/core gene of hepatitis B virus genotypes E and A in West Africa: new subtypes, mixed infections and recombinations. J Gen Virol 2006, 87:1163-73.
• [34]Mendy ME, Welzel T, Lesi OA, Hainaut P, Hall AJ, Kuniholm MH, et al.: Hepatitis B viral load and risk for liver cirrhosis and hepatocellular carcinoma in The Gambia, West Africa. J Viral Hepat 2010, 17:115-22.
• [35]Mbaye PS, Sarr A, Sire J-M, Evra M-L, Ba A, Daveiga J, et al.: Liver stiffness measurement and biochemical markers in Senegalese Chronic Hepatitis B patients with normal ALT and high viral load. PLoS One 2011., 6Article ID e22291
• [36]Zhao S-S, Tang L-H, Dai X-H, Wang W, Zhou R-R, Chen L-Z, et al.: Comparison of the efficacy of tenofovir and adefovir in the treatment of chronic hepatitis B: a systematic review. Virol J 2011, 8:111. BioMed Central Full Text
• [37]Quaye IK: Haptoglobin, inflammation and disease. Trans R Soc Trop Med Hyg 2008, 102:735-42.
• [38]Szymańska K, Lesi OA, Kirk GD, Sam O, Taniere P, Scoazec J-Y, et al.: Ser-249TP53 mutation in tumour and plasma DNA of hepatocellular carcinoma patients from a high incidence area in the Gambia, West Africa. Int J Cancer 2004, 110:374-9.