HBV genotypes prevalence, precore and basal core mutants in Morocco

Baha, Warda; Ennaji, Moulay Mustapha; Lazar, Fatiha; Melloul, Marouane; Fahime, Elmostafa El; Malki, Abdelouahad El; Bennani, Abdelouaheb

doi:10.1016/j.meegid.2012.04.026

Cited by 25 publications

(30 citation statements)

References 36 publications

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“…HBV/A2 has been observed also in North Africa where HBV genotype D is predominant [48–50]. Besides Africa, HBV/A1 was observed also in South Asia [46,47].…”

Section: Discussionmentioning

confidence: 99%

Disparate distribution of hepatitis B virus genotypes in four sub-Saharan African countries

Forbi¹,

Ben-Ayed²,

Xia³

et al. 2013

Journal of Clinical Virology

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Background Hepatitis B virus (HBV) places a substantial health burden on Africa. Here, we investigated genetic diversity of HBV variants circulating in 4 countries of sub-Saharan Africa using archived samples. In total, 1492 plasma samples were tested from HIV-infected individuals and pregnant women, among which 143 (9.6%) were PCR-positive for HBV DNA (Côte d’Ivoire, 70/608 [11.5%]; Ghana, 13/444 [2.9%]; Cameroon, 33/303 [10.9%]; and Uganda, 27/137 [19.7%]). Study design/results Phylogenetic analysis of the S-gene sequences identified HBV genotypes E (HBV/E, n = 96) and A (HBV/A, n = 47) distributed as follows: 87% of HBV/E and 13% of HBV/A in Côte d’Ivoire; 100% of HBV/E in Ghana; 67% of HBV/E and 33% of HBV/A in Cameroon; and 100% of HBV/A in Uganda. The average and maximal nucleotide distances among HBV/E sequences were 1.9% and 6.4%, respectively, suggesting a greater genetic diversity for this genotype than previously reported (p < 0.001). HBV/A strains were classified into subgenotypes HBV/A1, HBV/A2 and HBV/A3. In Uganda, 93% of HBV/A strains belonged to HBV/A1 whereas HBV/A3 was the only subgenotype of HBV/A found in Cameroon. In Côte d’Ivoire, HBV/A strains were classified as HBV/A1 (11.1%), HBV/A2 (33.3%) and HBV/A3 (55.6%). Phylogeographic analysis of the sequences available from Africa supported earlier suggestions on the origin of HBV/A1, HBV/A2 and HBV/A3 in East, South and West/Central Africa, respectively. Using predicted amino acid sequences, hepatitis B surface antigen (HBsAg) was classified into serotype ayw4 in 93% of HBV/E strains and adw2 in 68% of HBV/A strains. Also, 7.7% of the sequences carried substitutions in HBsAg associated with immune escape. Conclusions The observations of pan-African and global dissemination of HBV/A1 and HBV/A2, and the circulation of HBV/E and HBV/A3 almost exclusively in West and Central Africa suggest a more recent increase in prevalence in Africa of HBV/E and HBV/A3 compared to HBV/A1 and HBV/A2. The broad genetic heterogeneity of HBsAg detected here may impact the efficacy of prevention and control efforts in sub-Saharan Africa.

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“…HBV/A2 has been observed also in North Africa where HBV genotype D is predominant [48–50]. Besides Africa, HBV/A1 was observed also in South Asia [46,47].…”

Section: Discussionmentioning

confidence: 99%

Disparate distribution of hepatitis B virus genotypes in four sub-Saharan African countries

Forbi¹,

Ben-Ayed²,

Xia³

et al. 2013

Journal of Clinical Virology

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“…12.5% of HCC cases are attributable to HBV infection [7]. In addition, previous studies concerning HBV genotype distribution among Moroccan HBV carriers showed a predominance of genotype D, subgenotype D7 with limited circulation of genotype A, subgenotype A2 [8], [9].…”

Section: Introductionmentioning

confidence: 93%

Variability in the Precore and Core Promoter Regions of HBV Strains in Morocco: Characterization and Impact on Liver Disease Progression

et al. 2012

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BackgroundHepatitis B virus (HBV) is one of the most common human pathogens that cause aggressive hepatitis and advanced liver disease (AdLD), including liver cirrhosis and Hepatocellular Carcinoma. The persistence of active HBV replication and liver damage after the loss of hepatitis B e antigen (HBeAg) has been frequently associated with mutations in the pre-core (pre-C) and core promoter (CP) regions of HBV genome that abolish or reduce HBeAg expression. The purpose of this study was to assess the prevalence of pre-C and CP mutations and their impact on the subsequent course of liver disease in Morocco.Methods/Principal FindingsA cohort of 186 patients with HBeAg-negative chronic HBV infection was studied (81 inactive carriers, 69 with active chronic hepatitis, 36 with AdLD). Pre-C and CP mutations were analyzed by PCR-direct sequencing method. The pre-C stop codon G1896A mutation was the most frequent (83.9%) and was associated with a lower risk of AdLD development (OR, 0.4; 95% CI, 0.15–1.04; p = 0.04). HBV-DNA levels in patients with G1896A were not significantly different from the other patients carrying wild-type strains (p = 0.84). CP mutations C1653T, T1753V, A1762T/G1764A, and C1766T/T1768A were associated with higher HBV-DNA level and increased liver disease severity. Multiple logistic regression analysis showed that older age (≥40 years), male sex, high viral load (>4.3 log10 IU/mL) and CP mutations C1653T, T1753V, A1762T/G1764A, and C1766T/T1768A were independent risk factors for AdLD development. Combination of these mutations was significantly associated with AdLD (OR, 7.52; 95% CI, 4.8–8; p<0.0001).ConclusionsThis study shows for the first time the association of HBV viral load and CP mutations with the severity of liver disease in Moroccan HBV chronic carriers. The examination of CP mutations alone or in combination could be helpful for prediction of the clinical outcome.

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“…Ghosh et al described 13 HBV(+) patients with D5 subgenotype from a primitive tribal community in eastern India (15). It has been also reported from Morocco and Russia and Baltic region [57,58,74]. D6: It has been reported as a rare subgenotype from Indonesia, Kenya, Russia and Baltic region [22][23][24][25][26]54,55,74].…”

Section: Subgenotypes Of Genotype Dmentioning

confidence: 99%

“…Subgenotype D7 corresponds to nearly two thirds of all genotype D strains in these countries [57,58,62,63]. In Madagascar, in a study of 45 patients, 8 had D7 subgenotype [56].…”

Section: Subgenotypes Of Genotype Dmentioning

confidence: 99%