Variability in the precore and core promoter regions of HBV strains in Morocco: characterization and impact on liver disease progression.
BACKGROUND
Hepatitis 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.


RESULTS
A 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 log(10) 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).


CONCLUSIONS
This 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.
Laboratoire des Hépatites Virales, Institut Pasteur du Maroc, Casablanca, Morocco.
Bouchra
B
Kitab
Abdellah
A
Essaid El Feydi
Rajaa
R
Afifi
Christian
C
Trepo
Mustapha
M
Benazzouz
Wafaa
W
Essamri
Fabien
F
Zoulim
Isabelle
I
Chemin
Hanane Salih
HS
Alj
Sayeh
S
Ezzikouri
Soumaya
S
Benjelloun
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006509:Hepatitis B / Q000473:pathology* / Q000821:virology*; D006512:Hepatitis B Core Antigens / Q000235:genetics*; D006801:Humans; D008107:Liver Diseases / Q000473:pathology* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009018:Morocco; D009154:Mutation; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012044:Regression Analysis; D017422:Sequence Analysis, DNA
D006512:Hepatitis B Core Antigens