Molecular characterization of hepatitis B virus in liver disease patients and asymptomatic carriers of the virus in Sudan

Abstract

BackgroundHepatitis B virus is hyperendemic in Sudan. Our aim was to molecularly characterize hepatitis B virus from Sudanese individuals, with and without liver disease, because genotypes play an important role in clinical manifestation and treatment management.MethodsNinety-nine patients - 30 asymptomatic, 42 cirrhotic, 15 with hepatocellular carcinoma, 7 with acute hepatitis and 5 with chronic hepatitis- were enrolled. Sequencing of surface and basic core promoter/precore regions and complete genome were performed.ResultsThe mean ± standard deviation, age was 45.7±14.8 years and the male to female ratio 77:22. The median (interquartile range) of hepatitis B virus DNA and alanine aminotransferase levels were 2.8 (2.2-4.2) log IU/ml and 30 (19–49) IU/L, respectively. Using three genotyping methods, 81/99 (82%) could be genotyped. Forty eight percent of the 99 patients were infected with genotype D and 24% with genotype E, 2% with putative D/E recombinants and 7% with genotype A. Patients infected with genotype E had higher frequency of hepatitis B e antigen-positivity and higher viral loads compared to patients infected with genotype D. Basic core promoter/precore region mutations, including the G1896A in 37% of HBeAg-negative individuals, could account for hepatitis B e antigen-negativity. Pre-S deletion mutants were found in genotypes D and E. Three isolates had the vaccine escape mutant sM133T.ConclusionSudanese hepatitis B virus carriers were mainly infected with genotypes D or E, with patients infected with genotype E having higher HBeAg-positivity and higher viral loads. This is the first study to molecularly characterize hepatitis B virus from liver disease patients in Sudan.

Genotyping and virological characteristics of hepatitis B virus in HIV-infected individuals in Sudan

“…[23][24][25] In Sudan, close to 60% of liver disease patients were found to be infected with genotype D (predominantly subgenotype D1), 30% with genotype E, 8.5% with genotype A, and 2.5% with D/E recombinant. 26 In contrast, in Sudanese blood donors, genotype E was found to predominate (55%), followed by genotype D (39%), D/ E recombinant (4%), and genotype A (2%). 3 No information exists regarding the distribution of HBV genotypes in HIV-infected individuals in Sudan.…”

Genotypes and Genetic Variability of Hepatitis B Virus

“…Subgenotype D4, which is found in aboriginal populations in Papua New Guinea and Australia [12] and in a small percentage of the Canadian Inuit population [29], may be an early subgenotype dating from the time of early human intercontinental migrations. Moreover, a recombinant of subgenotype D4 has been identified in Sudan [30]. It is possible that D4 originated in Africa but has subsequently been replaced by other subgenotypes of D and the recombinant is a remnant of the original strain/s [30].…”

“…Moreover, a recombinant of subgenotype D4 has been identified in Sudan [30]. It is possible that D4 originated in Africa but has subsequently been replaced by other subgenotypes of D and the recombinant is a remnant of the original strain/s [30]. Subgenotype D4 carriers were significantly older than both D3 and B6 carriers [23].…”

“…Patients infected with genotypes A, B, D, and F show earlier and more frequent spontaneous HBeAg seroconversion compared to those infected with genotype C, independent of ethnicity [48,51,52]. Patients infected with genotype E have a higher frequency of HBeAg positivity and higher viral loads compared to patients infected with genotype D [30]. Individuals infected with subgenotype A1 lose HBeAg much earlier than those infected with subgenotype A2 [53].…”

“…Alaskans infected with genotype C or F are more likely to revert to HBeAg positivity and therefore are at more risk at developing severe liver disease than those infected with genotypes A, B, and D [52]. In Sudan, genotype E is found to prevail in asymptomatic blood donors [65], whereas genotype D predominates in liver disease patients [30]. Occult HBV infection, characterized by low viral loads, is common in patients infected with genotype H, and the development of HCC is rare [37].…”