Occult hepatitis B virus infection in HIV positive patients at a tertiary healthcare unit in eastern India.
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ABSTRACT:
SUBMITTER: Saha D
PROVIDER: S-EPMC5462430 | biostudies-literature | 2017
REPOSITORIES: biostudies-literature
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Occult hepatitis B virus infection in HIV positive patients at a tertiary healthcare unit in eastern India.
Saha Debraj D Pal Ananya A Sarkar Neelakshi N Das Dipanwita D Blackard Jason T JT Guha Subhasish Kamal SK Saha Bibhuti B Chakravarty Runu R
PloS one 20170607 6
Occult HBV infection (OBI), defined by the presence of HBV DNA in absence of hepatitis B surface antigen (HBsAg), is a significant concern in the HIV-infected population. Of 441 HIV+/HBsAg- patients analyzed, the overall prevalence of OBI was 6.3% (28/441). OBI was identified in 21 anti-HBc positives (17.8%), as well as among those who lacked any HBV-specific serological markers (2.2%). Comparison with HIV/HBV co-infection revealed that the levels of CD4, ALT, and HBV DNA were significantly lowe ...[more]
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Project description:Background & objectivesIndia has the third highest burden of HIV and highest number of cervical cancer in the world. A cross-sectional study was performed to determine the prevalence and types of human papillomavirus (HPV) infection, and the factors associated with HPV infection and abnormal cervical cytology in HIV-positive women attending the Antiretroviral Therapy (ART) Centre in a tertiary care hospital in eastern India.MethodsWe screened 216 HIV- positive women with Papanicolau smear cytology and HPV testing. HPV DNA was detected by using consensus primers followed by sequencing.ResultsOf the 216 HIV-positive women screened, 58 (26.85%) were HPV-positive; 56 (25.9%) were of high-risk (HR) HPV type. The most prevalent HPV type was HPV-16 (7.9%); non 16 and 18 HPV types were present in 17.6 per cent patients. Age ≤ 35 yr [(OR), 2.56 (1.26-5.19)], illiteracy [OR, 2.30 (1.19-4.46)], rural residence [OR, 3.99 (1.27-12.56)] and CD4 ≤ 350/µl [OR, 2.46 (1.26-4.83)] were associated with increased risk of acquisition of HPV. One hundred thirty nine (74.33%) patients had normal/ negative for intraepithelial lesions (NILM) cytology, three (1.60%) had atypical squamous cells of undetermined significance (ASCUS), 32 (17.11%) had low-grade squamous intraepithelial lesions (LSIL), 10 (5.35%) had high-grade squamous intraepithelial lesions (HSIL) and three (1.60%) had carcinoma cervix. WHO clinical Stage III and IV [OR, 2.83 (1.07-7.49)] and CD4 ≤ 350/µl [OR, 2.84 (1.30-6.20)] were risk factors for abnormal cytology.Interpretation & conclusionsOur study showed 26.85 per cent HPV positivity in HIV infected women in this region, with HPV-16 as the commonest genotype. Abnormal cervical cytology was seen in about 25 per cent women. Regular Pap smear screening as recommended by the National AIDS Control Organization will help in early detection of cervical abnormalities in HIV- positive women.
| S-EPMC4822373 | biostudies-literature
Project description:Occult hepatitis B is characterized by the absence of hepatitis B surface antigen (HBsAg) but the presence of HBV DNA. Because diagnosis of hepatitis B virus (HBV) typically includes HBsAg detection, occult HBV remains largely undiagnosed. Occult HBV is associated with increased risk of hepatocellular carcinoma, reactivation to chronic HBV during immune suppression, and transmission during blood transfusion and liver transplant. The mechanisms leading to occult HBV infection are unclear, although viral mutations are likely a significant factor. In this study, sera from 394 HIV-positive South Africans were tested for HBV DNA and HBsAg. For patients with detectable HBV DNA, the overlapping surface and polymerase open reading frames (ORFs) were sequenced. Occult-associated mutations-those mutations found exclusively in individuals with occult HBV infection but not in individuals with chronic HBV infection from the same cohort or GenBank references-were identified. Ninety patients (22.8%) had detectable HBV DNA. Of these, 37 had detectable HBsAg, while 53 lacked detectable surface antigen. The surface and polymerase ORFs were cloned successfully for 19 patients with chronic HBV and 30 patients with occult HBV. In total, 235 occult-associated mutations were identified. Ten occult-associated mutations were identified in more than one patient. Additionally, 15 amino acid positions had two distinct occult-associated mutations at the same residue. Occult-associated mutations were common and present in all regions of the surface and polymerase ORFs. Further study is underway to determine the effects of these mutations on viral replication and surface antigen expression in vitro.
| S-EPMC4562318 | biostudies-literature
Project description: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.
| S-EPMC3834618 | biostudies-literature
Project description:ObjectiveThe study was designed to assess the hepatitis B virus (HBV) and hepatitis C virus (HCV) co-infection scenario among the human immunodeficiency virus (HIV) infected patients attending a tertiary healthcare unit in eastern India. Additionally, clinical and virological characterization of these viruses, prior to antiretroviral therapy (ART) initiation was also done for better understanding of the disease profile.MethodsPool of ART-naive HIV/HBV co-infected and HIV mono-infected patients, participating in two different studies, were included in this study. HBV DNA was detected by nested-PCR amplification followed by HBV genotype determination and HBV reverse transcriptase (RT) region amplification and direct sequencing for detecting drug resistance.ResultsThe prevalence of HBsAg (11.3%) was higher compared to anti-HCV (1.9%) among the HIV infected ART-naive patients. Moreover, majority of the HBeAg positive HIV/HBV co-infected patients (87.7%) had HBV DNA ?20,000 IU/ml with median HBV DNA significantly higher than that of HBeAg negative subjects (5.7 log10 IU/ml vs. 4.2 log10 IU/ml; p<0.0001). Multivariate analysis also showed that HBeAg-positive status was independently associated with higher HBV DNA level (p?=?<0.001). Notably, 60.9% of the HBeAg negative co-infected subjects had HBV DNA ?2,000 IU/ml of which 37.0% had HBV DNA ?20,000 IU/ml. Genotype HBV/D (68.2%) was the predominant genotype followed by HBV/A (24.3%) and HBV/C (7.5%). Anti-HBV drug resistant mutations were detected in two (3.8%) of the ART-naive patients.ConclusionThe prevalence of HIV/HBV co-infection was relatively higher in our study subjects. HBeAg testing might provide clue for early treatment initiation. Furthermore, HBeAg negative patients are also associated with high HBV DNA levels and therefore require appropriate medical attention. Pre-treatment screening for anti-HBV drug resistant mutations is not necessary before ART initiation.
| S-EPMC3758335 | biostudies-literature
Project description:ObjectiveTo investigate the prevalence of occult HBV infection (OBI) among children and to characterize virology of occult HBV, we conducted an epidemiological survey.Methods186 HB-vaccinated infants born to HBsAg-positive mothers were included in the study. Serological tests for HBV markers were performed using commercial ELISA kits. Real-time quantitative PCR and nested PCR were used to detect HBV DNA. PCR products of the C and pre-S/S regions were sequenced and analyzed.Results1.61% (3/186) infants were HBsAg positive, and 4.92% (9/183) infants were considered as occult infection. The viral load of mothers was associated with occult infection (P?=?0.020). Incomplete three-dose injections of HB vaccine was associated with HBV infection (P?=?0.022). Six OBI infants were positive for anti-HBs, but their titers were not greater than 100 mIU/mL. Seven isolated HBV pre-S/S sequences were obtained from nine OBI infants. Three of the sequences were genotype C, and four of the sequences were genotype C/D. Escape mutation S143L was found in the four sequences of genotype C/D. All seven sequences lacked G145R and other escape mutation in S region.ConclusionsOccult HBV infection was detected in anti-HBs positive infants born to HBsAg-positive mothers in China. Occult infection was associated with absent anti-HBs or with low anti-HBs level, high maternal viral loads and escape mutations in the S gene.
| S-EPMC3741317 | biostudies-literature
Project description:In Gabon, a central African country, human immunodeficiency virus (HIV) and hepatitis B virus (HBV) are endemic. In a recent study, conducted in a semi-urban area (Franceville, Gabon), HBV infection was found to be more prevalent among HIV infected individuals. This study aims to investigate the prevalence and genetic diversity of hepatitis B virus infection among HIV infected individuals, predominantly under antiretroviral therapy, living in fully urbanized area: Libreville, capital of Gabon. Serological and molecular tests were performed to detect HBV infection among patients living with HIV/AIDS (PLHA). We used Monolisa HBsAg ULTRA, Anti-HBc Plus and Anti-HBs Plus EIA kits for serological analyses. HBV DNA viral load (HBV DNA VL) was determined by real time PCR and molecular characterization of HBV strains was performed by sequencing and phylogenetic analysis of partial HBV surface and core genes. At all, 70.2% of patients were under antiretroviral therapy. The prevalence of HBsAg was 8.8% (43/487). Detectable HBV DNA was found in 69.7% (30/43) of HBsAg positive patients and in 17.5% (24/137) HBsAg negative patients. HBV DNA VL was significantly higher among patient with CD4 cell counts less than 200 cells/mm3 than those with CD4 cell counts greater than 500 cells/mm3 (p = 0.008). We confirmed the presence of HBV sub-genotypes QS-A3 (40%), and A4 (20%) and HBV-E genotype (40%). The percentage of resistance to Lamivudine was high (40%) and varied according to the M204V/I motif. Occult hepatitis B infection (OBI) was found in patients with isolated HBcAb and among patients who had completed their HBsAg seroconversion. We detected HBV DNA for one patient without any HBV serological marker. This study provides a new landmark for the comprehension of HBV infection in PLHA in urban areas. OBI enhances HBV DNA prevalence and should be investigated in all HBsAg negative individuals.
| S-EPMC5760027 | biostudies-literature
Project description:The prevalence of occult Hepatitis B virus (HBV) infection in children was considerably varied from 0.1-64% in different reports. In this study we aimed to investigate the prevalence of occult HBV infection among the children born to mothers with positive hepatitis B surface antigen (HBsAg) in Jiangsu, China. Serum samples were collected from 210 children of 207 mothers with positive HBsAg. HBV serological markers were detected by ELISA and HBV DNA was detected by nested PCR. Homology comparison of HBV sequences recovered from the child and mother was used to define the infection. Three children (1.43%) were positive for HBsAg, in whom the HBV pre S and S gene sequence in each child was identical to that in her mother. Of the 207 HBsAg-negative children, nine displayed HBV DNA positive by two nested PCR assays using primers derived from S and C genes. However, the sequence alignment showed that the sequences in each child were considerably different from those in his/her mother. Therefore, the sequences amplified from the children were very likely resultant from the cross-contaminations. Furthermore, the nine children with 'positive HBV DNA' were all negative for anti-HBc, and one had anti-HBs 3.42 mIU/ml and eight others had anti-HBs from 72 to >1000 mIU/ml, indicating that the nine children were less likely infected with HBV. Therefore, none of the 207 HBsAg-negative children of HBV-infected mothers was found to have occult HBV infection. We conclude that the prevalence of occult HBV infection in vaccinated children born to HBsAg positive mothers should be extremely low. We recommend that homology comparison of sequences recovered from the child and mother be used to define the occult HBV infection in children born to HBV infected mothers.
| S-EPMC4226608 | biostudies-literature
Project description:BackgroundOccult or latent hepatitis B virus (HBV) infection is defined as infection with detectable HBV DNA and undetectable surface antigen (HBsAg) in patients' blood. The cause of an overt HBV infection becoming an occult one is unknown. To gain insight into the mechanism of the development of occult infection, we compared the full-length HBV genome from a blood donor carrying an occult infection (d4) with global genotype D genomes.ResultsThe phylogenetic analysis of polymerase, core and X protein sequences did not distinguish d4 from other genotype D strains. Yet, d4 surface protein formed the evolutionary outgroup relative to all other genotype D strains. Its evolutionary branch was the only one where accumulation of substitutions suggests positive selection (dN/dS = 1.3787). Many of these substitutions accumulated specifically in regions encoding the core/surface protein interface, as revealed in a 3D-modeled protein complex. We identified a novel RNA splicing event (deleting nucleotides 2986-202) that abolishes surface protein gene expression without affecting polymerase, core and X-protein related functions. Genotype D strains differ in their ability to perform this 2986-202 splicing. Strains prone to 2986-202 splicing constitute a separate clade in a phylogenetic tree of genotype D HBVs. A single substitution (G173T) that is associated with clade membership alters the local RNA secondary structure and is proposed to affect splicing efficiency at the 202 acceptor site.ConclusionWe propose an evolutionary scenario for occult HBV infection, in which 2986-202 splicing generates intracellular virus particles devoid of surface protein, which subsequently accumulates mutations due to relaxation of coding constraints. Such viruses are deficient of autonomous propagation and cannot leave the host cell until it is lysed.
| S-EPMC2637267 | biostudies-literature
Project description:Hepatitis B Virus (HBV) manifests high genetic variability and is classifiable into ten genotypes (A-J). HBV infection can lead to variable clinical outcomes, ranging from self-limiting acute hepatitis to active chronic hepatitis, cirrhosis and hepatocellular carcinoma. The present study characterizes HBV strains circulating among patients with acute (AHB) and chronic HBV infection (CHB). Among a total of 653 HBsAg positive cases, 40 manifested acute infection. After sequencing the surface(S), basal core promoter/pre-core(BCP/PC) and the X gene regions, phylogenetic tree was constructed using MEGA4 by neighbor-joining method. Statistical robustness was established with bootstrap analysis. Nucleotide diversity was determined by Shannon entropy per site using the Entropy program of the Los Alamos National Laboratories. Analyses of acute patients revealed that HBV/D2 is the major circulating sub-genotype and commonly associated with sexual promiscuity and the age group between15-30 years. Comparison of AHB and CHB patients revealed that HBeAg positivity, ALT levels and genotype D were significantly high in AHB, whereas CHB patients were predominantly male, had a high viral load, and were commonly associated with genotype C. The frequencies of mutations in the S, BCP/PC, and X gene were low in AHB as compared to CHB. Drug resistant mutations were not detectable in the polymerase gene of AHB. Average nucleotide diversity in AHB was considerably low as compared to CHB. Further, the highest average ΔH (average difference in entropy between chronic and acute infection) was observed in the BCP/PC region implying that this region was most vulnerable to mutations upon HBV persistence, especially in case of genotype C. Additionally, among all substitutions, the A1762T and G1764A BCP mutations were the strongest indicators of chronicity. In conclusion, the study exhibits a general portrait of HBV strains circulating among acute hepatitis B patients in Eastern India and their intricate differences with chronic patients which should be useful from the clinical point of view.
| S-EPMC4646492 | biostudies-literature
Project description:Occult hepatitis B virus infection (OBI), characterized as the persistence of hepatitis B virus (HBV) surface antigen (HBsAg) seronegativity and low viral load in blood or liver, is a special form of HBV infection. OBI may be related mainly to mutations in the HBV genome, although the underlying mechanism of it remains to be clarified. Mutations especially within the immunodominant "α" determinant of S protein are "hot spots" that could contribute to the occurrence of OBI via affecting antigenicity and immunogenicity of HBsAg or replication and secretion of virion. Clinical reports account for a large proportion of previous studies on OBI, while functional analyses, especially those based on full-length HBV genome, are rare.
| S-EPMC4814639 | biostudies-literature