Characterization of occult hepatitis B virus infection among HIV positive patients in Cameroon

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Abstract

Purpose

Occult hepatitis B infection (OBI) among HIV positive patients varies widely in different geographic regions. We undertook a study to determine the prevalence of occult hepatitis B infection among HIV infected individuals visiting a health facility in South West Cameroon and characterized occult HBV strains based on sequence analyses.

Methods

Plasma samples (n = 337), which previously tested negative for hepatitis B surface antigen (HBsAg), were screened for antibodies against hepatitis B core (anti-HBc) and surface (anti-HBs) antigens followed by DNA extraction. A 366 bp region covering the overlapping surface/polymerase gene of HBV was then amplified in a nested PCR and the amplicons sequenced using Sanger sequencing. The resulting sequences were then analyzed for genotypes and for escape and drug resistance mutations.

Results

Twenty samples were HBV DNA positive and were classified as OBI giving a prevalence of 5.9%. Out of these, 9 (45%) were anti-HBs positive, while 10 (52.6%) were anti-HBc positive. Additionally, 2 had dual anti-HBs and anti-HBc reactivity, while 6 had no detectable HBV antibodies. Out of the ten samples that were successfully sequenced, nine were classified as genotype E and one as genotype A. Three sequences possessed mutations associated with lamivudine resistance. We detected a number of mutations within the major hydrophilic region of the surface gene where most immune escape mutations occur.

Conclusions

Findings from this study show the presence of hepatitis B in patients without any of the HBV serological markers. Further prospective studies are required to determine the risk factors and markers of OBI.

Electronic supplementary material

The online version of this article (doi:10.1186/s12981-017-0136-0) contains supplementary material, which is available to authorized users.

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Most cited references 22

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Epidemiology of viral hepatitis and HIV co-infection.

Miriam J Alter (2006)

Worldwide, hepatitis B virus (HBV) accounts for an estimated 370 million chronic infections, hepatitis C virus (HCV) for an estimated 130 million, and HIV for an estimated 40 million. In HIV-infected persons, an estimated 2-4 million have chronic HBV co-infection and 4-5 million have HCV co-infection. HBV, HCV and HIV share common routes of transmission, but they differ in their prevalence by geographic region and the efficiency by which certain types of exposures transmit them. Among HIV-positive persons studied from Western Europe and the USA, chronic HBV infection has been found in 6-14% overall, including 4-6% of heterosexuals, 9-17% of men who have sex with men (MSM), and 7-10% of injection drug users. HCV infection has been found in 25-30% of HIV-positive persons overall; 72-95% of injection drug users, 1-12% of MSM and 9-27% of heterosexuals. The characteristics of HIV infected persons differ according to the co-infecting hepatitis virus, their epidemiologic patterns may change over time, and surveillance systems are needed to monitor their infection patterns in order to ensure that prevention measures are targeted appropriately.

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Hepatitis B virus and human immunodeficiency virus co-infection in sub-Saharan Africa: a call for further investigation.

Brian G. Leroux, M. Jeffrey Mphahlele, Dan Burnett … (2005)

A growing body of evidence indicates that human immunodeficiency virus (HIV)-positive individuals are more likely to be infected with hepatitis B virus (HBV) than HIV-negative individuals, possibly as a result of shared risk factors. There is also evidence that HIV-positive individuals who are subsequently infected with HBV are more likely to become HBV chronic carriers, have a high HBV replication rate, and remain hepatitis Be antigen positive for a much longer period. In addition, it is evident that immunosuppression brought about by HIV infection may cause reactivation or reinfection in those previously exposed to HBV. Furthermore, HIV infection exacerbates liver disease in HBV co-infected individuals, and there is an even greater risk of liver disease when HIV and HBV co-infected patients are treated with highly active anti-retroviral therapy (HAART). Complicating matters further, there have been several reports linking HIV infection to 'sero-silent' HBV infections, which presents serious problems for diagnosis, prevention, and control. In sub-Saharan Africa, where both HIV and HBV are endemic, little is known about the burden of co-infection and the interaction between these two viruses. This paper reviews studies that have investigated HIV and HBV co-infection in sub-Saharan Africa, against a backdrop of what is currently known about the interactions between these two viruses. Copyright Blackwell Munksgaard 2005

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High risk of occult hepatitis B virus infection in HIV-positive patients from South Africa.

M. Jeffrey Mphahlele, Lucky Moropeng, Johannes Ngobeni … (2005)

This was a retrospective, unmatched case control, laboratory-based study, investigating the impact of human immunodeficiency virus (HIV) infection on the outcome of routine laboratory detection of HBsAg and prevalence of active HBV infection in 295 samples from 167 HIV-positive and 128 HIV-negative patients. The samples were tested for HBV (HBsAg, anti-HBc, anti-HBs, HBeAg and anti-HBe) and anti-HIV 1 and 2 (Axsym assays, Abbott Laboratories), as part of routine diagnosis. A nested PCR assay, with detection limit of 800 copies/ml and employing independent sets of primers to core and surface genes, was used to investigate HBV DNA. Quantification of HBV DNA was determined with the Cobas Amplicor HBV Monitor assay (Roche Diagnostics). Of the 295 samples, the frequency of anti-HBc was almost similar; 82% for the HIV-negatives and 85% for the HIV-positives, indicating that both groups were equally exposed to HBV infection. The HIV-positives had a higher rate of anti-HBs (76.0% versus 47.7%) and a lower rate of HBsAg carriage (16.2% versus 35.2%), suggesting that HIV-positive individuals are less likely to experience chronic HBV infection. However, analysis of HBV DNA indicated that many of the anti-HBs positives (20.5% versus 8.2%) and HBsAg-negatives (22.1% versus 2.4%) had active HBV infection in the HIV-positive group. There was a statistically significant difference in the prevalence of HBV DNA in the HBsAg-negatives between the two groups (Odds ratio: 11.52; chi-square: p=0.00006). Additionally, 33.3% (5/15) of sera with "anti-HBc alone" serological pattern were HBV viremic in the HIV-positive group, compared to 0% (n=31) in the HIV-negatives. Quantification of HBV DNA from HBsAg-negative/HIV-positive patients demonstrated low level HBV viremia (below 10,000 copies/ml). In conclusion, these findings strongly support that HIV infection is a risk factor for occult HBV infections.

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Author and article information

Contributors

George Gachara: ggachara@gmail.com

Tshifhiwa Magoro: magorotshifhiwa@gmail.com

Lufuno Mavhandu: Lufuno.Mavhandu@univen.ac.za

Emmaculate Lum: ngongpanemma@yahoo.co.uk

Helen K. Kimbi: hkimbi@yahoo.co.uk

Roland N. Ndip: ndip3@yahoo.com

Pascal O. Bessong: +27737985920 , bessong@univen.ac.za , pascal.bessong@gmail.com

Journal

Journal ID (nlm-ta): AIDS Res Ther

Journal ID (iso-abbrev): AIDS Res Ther

Title: AIDS Research and Therapy

Publisher: BioMed Central (London )

ISSN (Electronic): 1742-6405

Publication date (Electronic): 8 March 2017

Publication date PMC-release: 8 March 2017

Publication date Collection: 2017

Volume: 14

Electronic Location Identifier: 11

Affiliations

[1 ]ISNI 0000 0004 0610 3705, GRID grid.412964.c, HIV/AIDS & Global Health Research Program, Department of Microbiology, , University of Venda, ; Private Bag X5050, Thohoyandou, 0950 Limpopo South Africa

[2 ]ISNI 0000 0000 8732 4964, GRID grid.9762.a, Department of Medical Laboratory Sciences, , Kenyatta University, ; Nairobi, Kenya

[3 ]ISNI 0000 0001 2288 3199, GRID grid.29273.3d, Department of Zoology and Animal Physiology, Faculty of Science, , University of Buea, ; Buea, Cameroon

[4 ]ISNI 0000 0001 2173 8504, GRID grid.412661.6, Department of Biological Sciences, Higher Teachers’ Training College, , University of Yaounde, ; Yaounde, Cameroon

[5 ]GRID grid.449799.e, Department of Medical Laboratory Science, Faculty of Health Sciences, , University of Bamenda, ; Bambili, Bamenda, Cameroon

[6 ]ISNI 0000 0001 2152 8048, GRID grid.413110.6, Department of Biochemistry and Microbiology, Faculty of Science and Agriculture, , University of Fort Hare, ; Alice, South Africa

[7 ]ISNI 0000 0001 2288 3199, GRID grid.29273.3d, Department of Microbiology and Parasitology, , University of Buea, ; Buea, Cameroon

Article

Publisher ID: 136

DOI: 10.1186/s12981-017-0136-0

PMC ID: 5341455

PubMed ID: 28270215

SO-VID: 42b21596-3af6-4bac-b0fe-6c4a1c30a48c

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 23 September 2016

Date accepted : 15 February 2017

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100001322, South African Medical Research Council;

Funded by: FundRef http://dx.doi.org/10.13039/501100001321, National Research Foundation;

Funded by: FundRef http://dx.doi.org/10.13039/100000061, Fogarty International Center;

Award ID: D43 TW009359

Award Recipient : George Gachara

Custom metadata

ScienceOpen disciplines: Infectious disease & Microbiology

Keywords: hepatitis b virus,occult hepatitis b infection,hiv,cameroon

Data availability:

ScienceOpen disciplines: Infectious disease & Microbiology

Keywords: hepatitis b virus, occult hepatitis b infection, hiv, cameroon

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Characterization of occult hepatitis B virus infection among HIV positive patients in Cameroon

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Abstract

Purpose

Methods

Results

Conclusions

Electronic supplementary material

Related collections

Point-Of-Care Testing for Hepatitis

Most cited references 22

Epidemiology of viral hepatitis and HIV co-infection.

Hepatitis B virus and human immunodeficiency virus co-infection in sub-Saharan Africa: a call for further investigation.

High risk of occult hepatitis B virus infection in HIV-positive patients from South Africa.

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Cited by 16

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