Hepatitis B genotypes/subgenotypes and MHR variants among Moroccan chronic carriers.

International audienceOBJECTIVES: The aim of this study was to determine the prevalence of Hepatitis B Virus (HBV) genotypes, subgenotypes, HBV surface antigen (HBsAg) subtypes and naturally occurring mutations in Major Hydrophilic region (MHR) of HBsAg among Moroccan patients with chronic HBV infection. METHODS: The study included 200 patients chronically infected with HBV. The HBV genotypes, subgenotypes, HBsAg subtypes and MHR variants were determined by direct sequencing of the HBV surface (S) gene and phylogenetic analysis. RESULTS: The S gene was successfully amplified in 134 patients. The mean age was 40.6 ± 12.2 years. Genotype D was predominant (90%, 120/134) and genotype A was less frequent (10%, 14/134). Genotype D strains belonged to subgenotypes D7 (70.8%, 85/120), D1 (25.8%, 31/120) and D2 (0.9%, 1/120). Three strains (2.5%) could not be classified in any subgenotype of genotype D. All genotype A strains belonged to subgenotype A2. HBsAg subtypes found were ayw2 (82.1%, 110/134), adw2 (10.4%, 14/134), ayw3 (3%, 4/134) and ayw4 (3%, 4/134). The global prevalence of MHR variants was 15% (20/134) with substitution P120T/S the most frequent (3.7%, 5/134). The occurrence of MHR variants was significantly associated with advancing age (>40 years) (p = 0.003) and independent of sex, HBeAg status, viral load, genotype, subgenotype and HBsAg subtype. CONCLUSIONS: This study provides the first description of predominance of HBV subgenotype D7/subtype ayw2 among Moroccan HBV chronic carriers. It also showed a significant prevalence of naturally occurring MHR variants in Morocco

Control of progression towards liver fibrosis and hepatocellular carcinoma by SOCS3 polymorphisms in chronic HCV-infected patients

International audienceChronic Hepatitis C is one of the most important risk factors of liver cirrhosis and hepatocellular carcinoma. Before reaching these ultimate steps, insulin resistance triggered by hepatitis C virus infection is known to participate in the progression of liver disease. The present study aims to investigate the influence of two functional polymorphisms on SOCS3 mRNA expression and on the outcomes of CHC progression in a North African context

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

<div><h3>Background</h3><p>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.</p> <h3>Methods/Principal Findings</h3><p>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; <em>p</em> = 0.04). HBV-DNA levels in patients with G1896A were not significantly different from the other patients carrying wild-type strains (<em>p</em> = 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; <em>p</em><0.0001).</p> <h3>Conclusions</h3><p>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.</p> </div

Multiple logistic regression analysis for factors independently associated with AdLD development

<p>Multiple logistic regression analysis for factors independently associated with AdLD development</p

Baseline characteristics of patients

<p>Abbreviations: IC = inactive HBsAg carriers; ACH = active chronic hepatitis; AdLD = Advanced liver disease; ALT = alanine aminotransferase; IU = international units; ND = not determined.</p>*<p>AdLD <i>vs</i> non-AdLD, <i>p</i> = 0.0001</p>†<p>AdLD <i>vs</i> non-AdLD, <i>p</i><0.0001</p>‡<p>IC <i>vs</i> ACH, <i>p</i><0.001; IC <i>vs</i> AdLD, <i>p</i><0.0001; ACH <i>vs</i> AdLD, <i>p</i> = 0.735</p>§<p>IC <i>vs</i> ACH, <i>p</i><0.0001; IC <i>vs</i> AdLD, <i>p</i><0.0001; ACH <i>vs</i> AdLD, <i>p</i> = 0.029</p>¶<p>IC <i>vs</i> ACH, <i>p</i> = 0.798; IC <i>vs</i> AdLD, <i>p</i> = 0.566; ACH <i>vs</i> AdLD, <i>p</i> = 0.361</p><p>∥ IC <i>vs</i> ACH, <i>p</i> = 0.798; IC <i>vs</i> AdLD, <i>p</i> = 0.361; ACH <i>vs</i> AdLD, <i>p</i> = 0.361</p>**<p>IC <i>vs</i> ACH, <i>p</i> = 0.416; IC <i>vs</i> AdLD, <i>p</i> = 0.142; ACH <i>vs</i> AdLD, <i>p</i> = 0.483</p>††<p>Non-AdLD <i>vs</i> AdLD, <i>p</i> = 0.007</p

Prevalence of Pre-C and CP mutations according to HBV genotypes A and D.

<p>Prevalence of Pre-C and CP mutations according to HBV genotypes A and D.</p

Association of the PreC/CP mutational patterns with clinical status (A) and HBV-DNA level (B).

<p>Four patterns (preC−/CP−, preC+/CP−, preC−/CP+, and preC+/CP+) were defined based on the presence (+) or absence (−) of pre-C mutation G1896A and CP A1762T/G1764A double mutation. For HBV-DNA levels, the data are presented as box plots, illustrated as the median (horizontal line) and the range from the 25th to the 75th percentiles. Group 1 <i>vs</i> 2, <i>p</i> = 0.09, Group 3 <i>vs</i> 1, <i>p</i> = 0.009; Group 3 <i>vs</i> 2, <i>p</i> = 0.02; Group 3 <i>vs</i> 4, <i>p</i> = 0.627; Group 4 <i>vs</i> 2, <i>p</i> = 0.02.</p

Prevalence of mutations in the Pre-C and CP regions among different clinical groups

<p>Abbreviations: IC = inactive HBsAg carriers; ACH = active chronic hepatitis; AdLD = advanced liver disease; OM = others mutations; TIM = translation initiation mutation (nts 1814–1819).</p>*<p>IC <i>vs</i> ACH, <i>p</i> = 0.189; AdLD <i>vs</i> non-AdLD, <i>p</i> = 0.04</p>†<p>IC <i>vs</i> ACH, <i>p</i> = 0.251; IC <i>vs</i> AdLD, <i>p</i> = 0.03; ACH <i>vs</i> AdLD, <i>p</i> = 0.114</p>‡<p>IC <i>vs</i> ACH, <i>p</i> = 0.251; IC <i>vs</i> AdLD, <i>p</i><0.0001; ACH <i>vs</i> AdLD, <i>p</i> = 0.0005</p>§<p>IC <i>vs</i> ACH, <i>p</i> = 0.001; IC <i>vs</i> AdLD, <i>p</i><0.0001; ACH <i>vs</i> AdLD, <i>p</i> = 0.02</p>¶<p>IC <i>vs</i> ACH, <i>p</i> = 0.0003; IC <i>vs</i> AdLD, <i>p</i><0.0001; ACH <i>vs</i> AdLD, <i>p</i> = 0.003</p><p>∥ ACH <i>vs</i> AdLD, <i>p</i> = 0.014</p

Frequency of multiple mutations in the CP region among patients at different stages of liver disease.

<p>Wild-type represents strains without mutations in indicated sites.</p