Hepatitis B virus subgenotypes and basal core promoter mutations in Indonesia

Abstract

AIM:To identify the distribution of hepatitis B virus (HBV) subgenotype and basal core promoter (BCP) mutations among patients with HBV-associated liver disease in Indonesia. METHODS:Patients with chronic hepatitis (CH, n = 61), liver cirrhosis (LC, n = 62), and hepatocellular carcinoma (HCC, n = 48) were included in this study.HBV subgenotype was identified based on S or preS gene sequence, and mutations in the HBx gene including the overlapping BCP region were examined by direct sequencing. RESULTS:HBV genotype B (subgenotypes B2, B3, B4, B5 and B7) the major genotype in the samples, accounted for 75.4%, 71.0% and 75.0% of CH, LC and HCC patients, respectively, while the genotype C (subgenotypes C1, C2 and C3) was detected in 24.6%, 29.0%, and 25.0% of CH, LC, and HCC patients, respectively. Subgenotypes B3 (84.9%) and C1 (82.2%) were the main subgenotype in HBV genotype B and C, respectively. Serotype adw2 (84.9%) and adrq+ (89.4%) were the most prevalent in HBV genotype B and C, respectively. Double mutation (A1762T/G1764A) in the BCP was significantly higher in LC (59.7%) and HCC (54.2%) than in CH (19.7%), suggesting that this mutation was associated with severity of liver disease. The T1753V was also higher in LC (46.8%), but lower in HCC (22.9%) and CH (18.0%), suggesting that this mutation may be an indicator of cirrhosis. CONCLUSION:HBV genotype B/B3 and C/C1 are the major genotypes in Indonesia. Mutations in BCP, such as A1762T/G1764A and T1753V, might have an association with manifestations of liver disease.

High prevalence of hepatitis B virus genotype C/C1 in the Minangkabau ethnic group in Indonesia

“…HBV/C1 was commonly found in Southeast Asia (the western part of Indonesia, Malaysia, Thailand, Vietnam and Bangladesh) and Southern China [12,13,20,21,27]. The Malay populations in the western (Melayu Minangkabau) and southern parts (Melayu Jawa and Melayu Bugis) of the Peninsular Malaysia were believed to have had more historical and cultural links with the populations from the Indonesian archipelago [28].…”

“…They originated from and still mainly reside in the West Sumatra province of Sumatra Island [17]. Previous studies have shown that HBV genotype C is the most prevalent among HBV carriers in this population, which is different from other populations in Sumatra Island [12-14]. However, the numbers of subjects in these studies were low.…”

“…Genotype B is the predominant HBV genotype in Indonesia, followed by genotypes C, D, and A [12-14]. HBV/B is predominant in the western part of Indonesia, whilst HBV/C is dominant on the eastern part [13,14].…”

“…HBV/B is predominant in the western part of Indonesia, whilst HBV/C is dominant on the eastern part [13,14]. Mutations at the BCP region such as A1762T/G1764A and T1753V were found in high prevalence (59.5% and 40.5%, respectively) and were associated with severe liver disease [12]. In a more recent study, the prevalence of pre-S mutation in Indonesian population was also reported [15,16].…”

Ultradeep Sequencing for Detection of Quasispecies Variants in the Major Hydrophilic Region of Hepatitis B Virus in Indonesian Patients

“…Of the Indonesian viruses, some mutations in the HBV genome that are associated with severe liver disease have been reported, including mutations in the basal core promoter region (e.g., A1762T/G1764A and T1753V) (19)(20)(21) and the pre-S region (22,23). Several minor drug-resistant mutations of HBV in Indonesian treatment-naive patients with chronic hepatitis were recently detected using a deep sequencing method (24).…”