Hepatitis B virus subgenotypes D1 and D3 are prevalent in Pakistan

<p>Abstract</p> <p>Background</p> <p>As the hepatitis B genotyping is important for assessing its clinical implications and geographical distribution, the sub-genotypes have been found useful for determination of specific genomic markers related to hepatocarcinogenesis. In Pakistan, there is no reported data on molecular evolutionary analysis of HBV. A study was, therefore, much needed to evaluate the spectra of mutations present in the strains prevalent here.</p> <p>Findings</p> <p>to confirm specificity of PCR typing, phylogenetic analysis of the pre-S1 region and the divergence was studied through 13 sequences of 362 bp (accession number <ext-link ext-link-type="gen" ext-link-id="EF432765">EF432765</ext-link> – <ext-link ext-link-type="gen" ext-link-id="EF432777">EF432777</ext-link>). A total of 315 serum samples, selected from HBsAg positive patients representing the major ethnic groups, residing in Karachi, Sindh were tested for genotyping. Genotype D (219/315) was found to be the most prevalent (70%) amongst our patients. The rest of the genotypes A and a mixture of A and D (AD) were distributed as 20%, and 10% respectively. Phylogenetic tree demonstrated clustering of 11 samples with subgenotype D1 sequences and the remaining two strains on a branch within D3 samples. All samples intermixed with strains from other countries and were found to be closely related to Indian, Iranian and Egyptian HBV strains with 98.7 – 99.0% homology.</p> <p>Conclusion</p> <p>This study confirms the predominance of genotype D in southeastern Asia and presence of subgenotypes DI and D3 in the Pakistani infected patients. More studies are required to investigate the reason for fewer inclusions of D3 compared to the D1 in Pakistani HBV strains.</p

Drug Trafficking Routes and Hepatitis B in Injection Drug Users, Manipur, India

Prevalence of hepatitis B genotype C in injection drug users in the northeastern Indian state of Manipur, neighboring the "Golden Triangle," correlates well with overland drug-trafficking routes, the injection drug use epidemic, and the spread of HIV. Further spread to other regions of India through mobile populations is possible

Distribution of hepatitis B virus genotypes: Phylogenetic analysis and virological characteristics of Genotype C circulating among HBV carriers in Kolkata, Eastern India

Aim: To evaluate the genotype distribution of hepatitis B virus (HBV) in Eastern India and to clarify the phylogenetic origin and virological characteristics of the recently identified genotype C in this region. Methods: Genotype determination, T1762/A1764 mutation in the basal core promoter (BCP) and A1896 mutation in the precore region of 230 subjects were determined by restriction fragment length polymorphism method (RFLP) and the result was confirmed by direct sequencing. Results: The predominant genotypes D (HBV/D) and A (HBV/A) were detected in 131/230 (57%) and 57/230 (25%) samples. In addition, genotype C (HBV/C) was detected in 42/230 (18%) isolates. Surface gene region was sequenced from 45 isolates (27 HBV/C, 9 HBV/A and 9 HBV/D). Phylogenetic analysis revealed that all of the HBV/C sequences clustered with South East Asian subgenotype (HBV/Cs). The sequence data showed remarkable similarity with a Thai strain (AF068756) (99.5% ± 0.4% nucleotide identities) in 90% of the genotype C strains analyzed. T1762/A1764 mutation in BCP region, associated with high ALT was significantly higher in HBeAg negative isolates than HBeAg positive isolates. Frequency of A1896 mutation leading to HBeAg negativity was low. Conclusion: The present study reports the genotypic distribution and the characteristics of partial genome sequences of HBV/C isolates from Eastern India. Low genetic diversity and confinement of HBV/C in Eastern India possibly indicate a recent, limited, spread in this region. Genotype C with T1762/A1764 mutation has been reported to increase the risk for hepatocellular carcinoma; therefore genotype C carriers in Eastern India should be carefully monitored

Anti-hepatitis B core antigen testing with detection and characterization of occult hepatitis B virus by an in-house nucleic acid testing among blood donors in Behrampur, Ganjam, Orissa in southeastern India: implications for transfusion

<p>Abstract</p> <p>Background</p> <p>Occult hepatitis B virus (HBV) infection might transmit viremic units into the public blood supply if only hepatitis B surface antigen (HBsAg) testing is used for donor screening. Our aim was to evaluate the prevalence of occult HBV infection among the HBsAg negative/antiHBc positive donations from a highly HIV prevalent region of India.</p> <p>Methods</p> <p>A total of 729 HBsAg negative donor units were included in this study. Surface gene and precore region were amplified by in house nucleic acid test (NAT) for detection of occult HBV infection and surface gene was analyzed after direct sequencing.</p> <p>Results</p> <p>A total of 220 (30.1%) HBsAg negative donors were antiHBc positive, of them 66 (30%) were HBV DNA positive by NAT. HBV DNA positivity among 164 antiHBc only group, was 27.1% and among 40 antiHBs positive group was 30.0%. HBV/D (93.3%) was predominant and prevalence of both HBV/C and HBV/A was 3.3%. Single or multiple amino acids substitutions were found in 95% samples.</p> <p>Conclusion</p> <p>Thus, a considerable number of HBV infected donors remain undiagnosed, if only HBsAg is used for screening. Addition of antiHBc testing for donor screening, although will lead to rejection of a large number of donor units, will definitely eliminate HBV infected donations and help in reducing HBV transmission with its potential consequences, especially among the immunocompromised population. The HBV genetic diversity found in this donor population are in accordance with other parts of India.</p

Characterization of the Occult Hepatitis B Virus Variants Circulating among the Blood Donors from Eastern India

A previous study from West Bengal documented very high rate of occult HBV infection (OBI) among the HBsAg negative blood donors. This study was aimed to characterize the OBI strains circulating among the blood donors and to estimate the risk associated with the prevailing viral variants/mutants. Blood samples from 2195 voluntary blood donors were included in the study. HBsAg, HBeAg, anti-HBc, and anti-HBs statuses of the samples were done by ELISA based detection. PCR amplification and sequencing were done to determine HBV genotypes, basal core promoter (BCP), and precore (Pre-C) mutations. Among the study samples, 268 were anti-HBc positive/HBsAg negative, among which 65 (24.25%) were HBV DNA positive. Phylogenetic analysis revealed the presence of HBV/D (87.23%), HBV/A (8.51%), and HBV/C (4.26%) (P<0.0001). HBV/D3 (65.85%) was the significantly prevalent subgenotype over HBV/D2 (26.83%) and HBV/D1 (7.31%) (P=0.0003). Considerable prevalence of differential BCP (1752C, 1753C, 1762T/1764A, 1753C+1762T/1764A, 1773C, and 1814C) and reverse transcriptase (rt) gene (rtI91L, rtL93P, rtS106C, rtR110G, rtN118T, rtS119T, rtY126H, rtG127W/R, rtC136R, and rtY158H) mutations was identified. Association of specific HBV subgenotypes with OBI was interesting and needs further study. Clinically relevant mutations were prevalent among the OBI strains which are of serious concern

Characterization of the Occult Hepatitis B Virus Variants Circulating among the Blood Donors from Eastern India

A previous study from West Bengal documented very high rate of occult HBV infection (OBI) among the HBsAg negative blood donors. This study was aimed to characterize the OBI strains circulating among the blood donors and to estimate the risk associated with the prevailing viral variants/mutants. Blood samples from 2195 voluntary blood donors were included in the study. HBsAg, HBeAg, anti-HBc, and anti-HBs statuses of the samples were done by ELISA based detection. PCR amplification and sequencing were done to determine HBV genotypes, basal core promoter (BCP), and precore (Pre-C) mutations. Among the study samples, 268 were anti-HBc positive/HBsAg negative, among which 65 (24.25%) were HBV DNA positive. Phylogenetic analysis revealed the presence of HBV/D (87.23%), HBV/A (8.51%), and HBV/C (4.26%) ( &lt; 0.0001). HBV/D3 (65.85%) was the significantly prevalent subgenotype over HBV/D2 (26.83%) and HBV/D1 (7.31%) ( = 0.0003). Considerable prevalence of differential BCP (1752C, 1753C, 1762T/1764A, 1753C+1762T/1764A, 1773C, and 1814C) and reverse transcriptase (rt) gene (rtI91L, rtL93P, rtS106C, rtR110G, rtN118T, rtS119T, rtY126H, rtG127W/R, rtC136R, and rtY158H) mutations was identified. Association of specific HBV subgenotypes with OBI was interesting and needs further study. Clinically relevant mutations were prevalent among the OBI strains which are of serious concern

An insight into interaction of cell cycle regulating miRNAs and Hepatitis B virus X protein: DOI: 10.14800/rd.818

The perspective of disease development can often be attributed for deregulation of gene expression. Hepatocellular carcinoma (HCC) is the one of most common malignancies worldwide and chronic Hepatitis B Virus (HBV) infection is one of the major risk factors in development of HCC. Information about microRNA mediated regu­lation of viral infections is just emerging. MicroRNAs are about 19- 23 base pair long functional transcripts that regulate gene expression by cleavage or translational repression of target mRNA. Oncogenic (or tumor suppressive) roles of miRNA in many aspects of cancer biology and wide spread differential expression of miRNAs in different stages of HBV related Hepatocellular Carcinoma (HCC) compared with normal tissues are well documented. During HBV infection, perturbations of miRNA expression particularly cell cycle regulating miRNAs might have significant correlation with HCC development. Hepatitis B virus X protein (HBx) is a multifunctional protein that balances cell proliferation and programmed cell death by its anti and pro-apoptotic function. It affects transcriptional activation via its interaction with nuclear transcription factors as also cytoplasmic modulation in various signal transduction pathways contributing to cell proliferation and survival. HBx is often referred as oncoprotein for its crucial role in the development of HCC. HBx-miRNA interaction in HBV related HCC was the focus of much attention over last few years. HBx is found to modulate several miRNAs that are associated with HBV related HCC. This review concentrates on the interaction of HBx protein with some of the miRNAs that are essentially associated with cell proliferation and found modulated in HCC. HBx-miRNA interactions provide new insight into possible way by which viral protein acts through microRNA and thereby regulate host functioning. Finally, the HBx-miRNA interaction can be utilized as a therapeutic strategy for management of HBV related HCC