15 research outputs found
An investigation of hepatitis B virus in antenatal women tested for human immunodeficiency virus, in the Western Cape Province of South Africa
No full textThesis (MScMedSc)--Stellenbosch University, 2012.ENGLISH ABSTRACT: Hepatitis B virus (HBV) immunisation protocols in much of Africa are based on data from the pre-human immunodeficiency virus (pre-HIV) era that indicated that HBV transmission occurs predominantly horizontally between siblings and play-mates rather than vertically from mother to child. The immunosuppression associated with HIV infection however may release HBV from immune control resulting in higher HBV viral loads, which may increase the risk of perinatal mother to child transmission of HBV. The aim of this study was to determine the prevalence and characteristics of chronic HBV infection in HIV-infected pregnant women compared to HIV-uninfected pregnant women in the Western Cape province of South Africa.
Ethical approval was obtained to conduct a retrospective, matched case-control, unlinked anonymous study using residual plasma samples from the 9355 pregnant women included in the Western Cape's 2008 National HIV and Syphilis Antenatal Survey. Samples were tested for HBsAg on the AxSYM (Abbott, Chicago, IL) and confirmed by neutralization. Confirmed HBsAg-positive samples were tested for HBeAg, anti-HBe and anti-HD (Diasorin, Saluggia, Italy) and had HBV viral load and genotyping done. In addition, HBsAg-negative samples were tested for anti-HBc.
Samples from 1549 HIV-infected pregnant women were included and matched to the same number of samples from age- and race-matched HIV-uninfected women. Median age of 26 years, parity and education were similar in the two groups. The prevalence of HBsAg was 3.4% for the HIV-infected group and 2.9% for the HIV-uninfected group. HBV DNA loads of greater than 104 IU/ml were detected in 32.1% of HBsAg-positive, HIV/HBV co-infected women, and in 14.3% HBsAg positive, HBV mono-infected women. Among the HIV-infected group 18.9% of HBsAg-positive were HBeAg positive, with a median viral load of 7.93 log10 IU/ml; whilst 15.5% HIV-uninfected women were positive for HBeAg with a median viral load of 6.07 log10 IU/ml. Genotype A was seen in 92.6% of the isolates while 7.4% of the isolates were genotype D. Serum total anti-HBc antibodies that are a marker of past infection were detected in 42.2% of HIV-infected and in 24.1% of HIV-uninfected women that were negative for HBsAg. No positive sample for anti-HD was seen among all HBsAg-positive samples. This data indicates that there is increased exposure to HBV in HIV-infected pregnant women than in HIV-uninfected women and that a greater proportion of HIV-infected pregnant women compared to HBV mono-infected pregnant women may be at increased risk of transmitting HBV to their infants. Further studies are needed to determine the rate of vertical transmission of HBV in the HIV era.AFRIKAANSE OPSOMMING: Hepatitis B virus (HBV) immunisasie protokolle vir meeste dele van Afrika is gebaseer op data versamel in die era voor MIV. Die data dui aan dat HBV oordrag hoofsaaklik deur horisontale transmissie tussen broers, susters en speelmaats eerder as vertikale transmissie van moeder na kind plaasvind. Die onderdrukking van die immuunstelsel as gevolg van MIV infeksie kan egter lei tot 'n verhoogde risiko van perinatale HBV oordrag van moeder na kind. Die doel van hierdie studie was om die voorkoms en karakter van chroniese HBV infeksie in MIV-positiewe swanger vroue te vergelyk met die van MIV-negatiewe swanger vroue.
Etiese goedkeuring is verkry om 'n retrospektiewe, deursnee-, ongekoppelde anonieme studie uit te voer wat gebruik maak van oorblywende plasma monsters van 9355 swanger vroue wat ingesluit is in die Wes-Kaap 2008 Nasionale MIV en Sifilis Voorgeboortelike Opname. Die monsters was getoets vir HBsAg antiliggame (AxSYM, Abbott, Chicago, IL) en bevestig deur neutralisasie toetse. Positiewe monsters was getoets vir HBeAg en anti-HBe (Diasorin, Saluggia, Italië). HBV viruslading en genotipering was ook op HBsAg positiewe monsters gedoen. Die HBsAg negatiewe monsters was getoets vir die teenwoordigheid van anti-HBc.
Monsters van 1549 MIV-positiewe swanger vroue was ingesluit in die studie. Dieselfde aantal monsters van MIV-negatiewe vroue, met ooreenstemende ouderdom en etnisiteit, was ingesluit as kontroles. Die gemiddelde ouderdom van albei groepe was 26 jaar. Pariteit en opvoeding was dieselfde in albei groepe. Die voorkomssyfer van HbsAg was 3.4% in die MIV-positiewe groep en 2.8% in die MIV-negatiewe groep. HBV DNS ladings van meer as 104 IU/ml was waargeneem in 32.1% van die MIV-mede-geinfekteerde vroue en in 14.3% van die MIV-negatiewe groep. In die MIV-positiewe groep was 18.9% vroue HBeAg positief, met 'n gemiddelde virale lading van 7.93 log10 IU/ml, terwyl 15.5% MIV-negatiewe vroue positief was vir HBeAg met 'n gemiddelde virale lading van 6.07 log10 IU/ml. In ons studie was 92.6% van die monsters genotipe A en 7.4% genotipe D. Toatale anti-HBc antiliggame, 'n merker van vorige infeksie, was gevind in 42.2% van MIV-mede-geïnfekteerde vroue en 24.1% van MIV-negatiewe vroue wat negatief was vir HBsAg antiliggame.
Data van ons studie dui op 'n verhoogde risiko vir vertikale HBV transmissie van MIV-positiewe moeders na hul babas. Verdere studies word benodig om vas te stel of vertikale transmissie van HBV van MIV-positiewe vroue na hul babas plaasvind.Wellcome TrustPoliomyelitis Research Foundatio
Hepatitis B virus-associated hepatocellular carcinoma in South Africa: epidemiology and impact of HIV-1 co-infection and immune dysregulation
No full textThesis (PhD)--Stellenbosch University, 2016ENGLISH ABSTRACT : Co-infection with the human immunodeficiency virus (HIV) negatively impacts the natural progression of hepatitis B virus (HBV) infection, including causing rapid progression to liver fibrosis and hepatocellular carcinoma (HCC). In sub-Saharan Africa the overlap between high HIV and HBV prevalence may increase the incidence of HCC. The aim of this study was to investigate the effect of HIV co-infection on presentation of HCC among HBV-infected patients. Since HCC is thought to be driven by ongoing severe inflammation, the study also evaluated the association between the expression of markers of immune activation/exhaustion and liver inflammation in patients with chronic hepatitis B (CHB) to determine if the risk of hepatofibrosis is increased by exposure to gut microbial products and compared HIV-infected patients with HBV-infected and HIV-HBV co-infected patients.
Ethical approval was obtained to conduct two sub-studies. The first sub-study (HCC Epidemiology Study) involved recruitment of patients diagnosed with HCC at oncology units of selected teaching hospitals in South Africa. A total of 107 HCC cases were recruited between December 2012 and October 2015. Demographic, laboratory and clinical data together with blood specimens were collected. Patients were tested for HBV, hepatitis C virus (HCV) and HIV. Molecular characterization of HBV and HCV was also performed. For the second sub-study (Liver Fibrosis and Immune Markers Study), 46 HBV/HIV co-infected; 47 HBV monoinfected; 39 HIV monoinfected and; 39 HIV-/HBV-uninfected controls were recruited following informed consent. All HIV-infected patients had been on highly active antiretroviral therapy (HAART) for ≥3 months. Liver stiffness measurements were taken using the Fibroscan 402. Cell-based immunomarkers of activation/exhaustion were measured using flow cytometry of fresh whole blood. Soluble serum/plasma immunomarkers were measured using ELISA and Luminex. HIV and HBV viral loads and genotyping of HBV were performed.
Of 107 cases in the HCC Epidemiology study, 83 (78%) were male and 68/106 (64%, 95% CI: 59-77) were positive for HBsAg. HIV seropositivity was seen in 22/100 (22%, 95% CI: 14-30) of all HCC cases. Among HBsAg-positive HCC cases, 19/66 (29%, 95% CI: 18-40) were HIV-infected compared to only 3/34 (9%) among those that were HBsAg-negative, p=0.04. The proportion of females among the HBV/HIV co-infected HCC cases 6/18 (33%, 95% CI: 11-55) was significantly higher compared to those that were HBV-mono-infected 6/47 (13%, 95% CI: 3-23), p=0.005. HIV/HBV co-infected females presented younger, at mean age 36.8 years (95% CI: 32.2-41.5) compared to 50.5 years (95% CI: 30.2-70.8) in HBV-mono-infected women, p=0.09. Males continue to be disproportionally affected with HCC. There is a trend towards younger age at diagnosis of HCC among HIV-positive compared to HIV-negative women.
The Liver Fibrosis and Immune Markers Study showed a high percentage of CD8+ T lymphocytes from co-infected subjects expressing HLA-DR/CD38 and PD-1 (p<0.05). Soluble CD14 and IP-10 were also significantly elevated in plasma of co-infected patients. Co-infected subjects exhibited delayed immune recovery with lower CD4/CD8 T cell ratio; CD4 cell counts and frequent HIV viremia compared to HIV mono-infected participants (p<0.05). The HBV mono-infected group had the highest proportion of participants with moderate/advanced liver fibrosis measured by Fibroscan, together with highest plasma concentrations of most of the cytokines measured. The results showed positive correlation between HIV and HBV viral replication and liver fibrosis. The results suggest that there is persistent T-lymphocyte dysregulation and delayed immune recovery in ART-experienced HBV/HIV co-infected patients. However this does not appear to be associated with severity of liver fibrosis in this cohort. HAART used in HIV is also effective against HBV and may therefore have led to control of viral replication leading to better fibrosis scores compared to the HBV mono-infected patients. Moderate/advanced liver fibrosis in HBV-mono-infection may well be an indicator of poor access to HBV screening and treatment.AFRIKAANSE OPSOMMING : Geen Afrikaanse opsomming geskikbaar nieDoctora
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Hepatitis B virus-associated hepatocellular carcinoma in South Africa in the era of HIV
No full textCITATION: Maponga, T. G., et al. 2020. Hepatitis B virus-associated hepatocellular carcinoma in South Africa in the era of HIV. BMC Gastroenterology, 20:226, doi:10.1186/s12876-020-01372-2.The original publication is available at https://bmcgastroenterol.biomedcentral.comBackground: Patients co-infected with hepatitis B virus (HBV) and the human immunodeficiency virus (HIV) are at
risk of developing hepatocellular carcinoma (HCC). In sub-Saharan Africa, the overlap between high HIV and HBV
prevalence may increase the incidence of HCC. This study investigated the impact of HBV/HIV co-infection on age
at presentation and survival of HCC.
Methods: Ethical approval was obtained to recruit, following informed written consent, patients diagnosed with
HCC at oncology units at four South African hospitals. Between December 2012 and August 2015, patients newly
diagnosed with HCC were recruited and provided demographic and clinical data and blood specimens. Patients
were tested for HBV, hepatitis C virus (HCV) and HIV. Survival data was available for a subset of patients.
Results: Of 107 HCC cases, 83 (78%) were male. Median age was 46 years (range 18 to 90 years), 68/106 (64%) were
HBsAg-positive, and 22/100 (22%) were HIV infected. Among HBV surface antigen (HBsAg)-positive HCC cases, 18/66
(27%) were HIV-infected compared to 3/34 (9%) among those that were HBsAg-negative (p = 0.04). A greater
proportion of HBV/HIV co-infected cases were female than HBV mono-infected (6/18, 33% vs 6/47, 13%; p = 0.005).
In addition, HBV/HIV co-infected females presented at a younger mean age (36.8 years) than HBV mono-infected
women (50.5 years) (p = 0.09). Median survival was 82 days among the HIV-infected HCC patients compared to 181
days among those without HIV (p = 0.15).
Conclusions: HCC is an important complication in the HIV/HBV infected patient. HIV-positive patients presented
with HCC at a younger age than HIV-negative patients, this effect appears to be greater in women. These data
provide more evidence supporting the call to address. HCC as a cause of morbidity and mortality in the HBV/HIV
co-infected patient population. (281 words).https://bmcgastroenterol.biomedcentral.com/articles/10.1186/s12876-020-01372-2Publisher's versio
Viral hepatitis associated hepatocellular carcinoma on the African continent, the past, present, and future: a systematic review
No full textAbstract Background Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths in Africa. In Africa, the major causes of HCC include chronic infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV). Knowledge of the changes in the incidence of viral hepatitis-associated HCC over time and the factors responsible for such changes is key in informing policies for the prevention of viral hepatitis-associated HCC in Africa. Aim The study aimed to systematically summarize the changes in the prevalence of viral hepatitis among HCC patients and the overall effect of the prevalence of viral hepatitis on the incidence of HCC over the past four decades in Africa (1980–2019). Methods A literature search was conducted in MEDLINE (PubMed), Google Scholar, Science Direct, Scopus, Web of Science, and African wide web for articles published on viral hepatitis-associated HCC in Africa from 1980 to 2019. The abstracts of the articles were screened for eligibility and those meeting the inclusion criteria were retrieved and reviewed. Results A total of 272 studies were included in the analysis. Viral hepatitis-related HCC incidence changed by 1.17% (95% confidence interval (CI): 0.63–1.71, p < 0.001), 0.82% (95% CI: 0.45–1.18, p < 0.001), and 3.34% (95% CI: 2.44–4.25, p < 0.001) for every 1% change in the prevalence of HBV, HCV, and hepatitis D virus (HDV) respectively, per decade. The incidence of HBV-related HCC decreased by − 0.50% (95% CI: − 0.74 – − 0.25, p < 0.001) over the last 40 years, while HCV-related HCC increased. Conclusion Overall, the incidence of viral hepatitis-associated HCC has not declined, mainly due to no decline in the prevalence of HCV, HDV, and the high number of chronic hepatitis B carriers on the African continent. There is an urgent need for the allocation of resources for the implementation of treatment and preventive programs for HBV, HCV, HDV, and HCC in Africa. This systematic review is registered with PROSPERO®, number CRD42020169723
Successful Treatment of a South African Pediatric Case of Acute Liver Failure Caused by Perinatal Transmission of Hepatitis B
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HBV and HIV viral load but not microbial translocation or immune activation are associated with liver fibrosis among patients in South Africa
No full textBackground: Co-infection with HIV negatively impacts the progression of chronic hepatitis B virus (HBV) infection, including causing rapid progression to liver fibrosis. Sub-Saharan Africa represents arguably the most important intersection of high endemicity of both chronic hepatitis B virus (HBV) infection and HIV infection. Methods: We recruited 46 HBV/HIV-co-infected; 47 HBV-monoinfected; 39 HIV-monoinfected; and 37 HBV/HIV-uninfected patients from Tygerberg Hospital, Cape Town, South Africa. All HIV-infected patients were on antiretroviral therapy for ≥3 months. Liver stiffness measurements were assessed using the Fibroscan (Fibroscan 402, Echosens). Cell-based immunomarkers were measured by flow cytometry. Soluble serum/plasma immunomarkers were measured by Luminex technology and enzyme immunoassays. HIV (COBAS/Ampliprep TaqMan HIV-1) and HBV viral loads (in-house assay) were also performed. Results: HBV/HIV co-infected patients showed significantly higher levels of immune activation %CD8+/HLA-DR+/CD38+ (median 30%, interquartile range: 17-53) and %CD8+/PD-1 (median 22%, interquartile range: 15-33), p ≤ 0.01 compared to all other study groups. Despite this, the HBV-mono-infected group had the highest proportion of patients with advanced liver fibrosis (≥13 kPa) as measured by Fibroscan (18%). HBV mono-infected patients showed highest expression of most cytokines including IL-17 and basic fibroblastic growth factor. There was significant positive correlation between detectable HIV and HBV viral replication and liver fibrosis but not immune activation or gut translocation. Discussion: Highly-active antiretroviral therapy, including tenofovir, is effective against both HIV and HBV. Earlier therapy in the co-infected patients may therefore have controlled viral replication leading to better fibrosis scores when compared to HBV mono-infection in this study. On-going HBV and HIV viraemia, rather than microbial translocation or immune activation, appear to be the drivers of liver fibrosis. Moderate to advanced liver fibrosis in HBV-mono-infection may well indicate poor access to screening and treatment of HBV infection
The lipidome in phenotyping hepatitis B infection (‘LiPHe-B’): preliminary results from our pilot study
No full textSimple treatment eligibility score for chronic HBV infection at peripheral health facilities in sub-Saharan Africa
No full textWED-006 Liver stiffness and AST-to-platelet ratio index (APRI) predict all- cause mortality in untreated people living with hepatitis B across Africa: a multi-centre cohort analysis in the hepatitis B in Africa collaborative network (HEPSANET)
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