Prevalence of hepatitis D virus infection in sub-Saharan Africa: a systematic review and meta-analysis

  • The Lancet Global Health, Volume 5, No. 10, Year 2017

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Study Justification:
– Hepatitis D virus (HDV) can establish a persistent infection in people with chronic hepatitis B, leading to accelerated progression of liver disease.
– In sub-Saharan Africa, where hepatitis B surface antigen (HBsAg) prevalence is high, HDV may be an important additive cause of chronic liver disease.
– The study aimed to establish the prevalence of HDV among HBsAg-positive populations in sub-Saharan Africa.
Study Highlights:
– Systematic review and meta-analysis of studies on HDV prevalence in sub-Saharan Africa.
– Included data from two HIV-positive cohorts in Ghana and Malawi to provide additional information where data were scarce.
– Found localized clusters of HDV endemicity across sub-Saharan Africa.
– Identified higher seroprevalence of HDV in liver-disease populations compared to general populations.
– Showed an increased risk of HDV detection in HBsAg-positive patients with liver fibrosis or hepatocellular carcinoma.
Study Recommendations:
– More epidemiological data are needed from southern and east Africa, as well as from patients with established liver disease.
– Further studies should aim to define the reliability of HDV testing methods, identify risk factors for transmission, and characterize the natural history of the infection in the region.
Key Role Players:
– Researchers and scientists specializing in viral hepatitis and liver disease.
– Public health officials and policymakers.
– Healthcare providers and clinicians.
– Laboratory technicians and diagnosticians.
– Community health workers and educators.
Cost Items for Planning Recommendations:
– Research funding for conducting epidemiological studies, laboratory testing, and data analysis.
– Training and capacity building for healthcare professionals and laboratory staff.
– Development and implementation of public health programs for prevention, diagnosis, and treatment of HDV.
– Surveillance systems for monitoring HDV prevalence and disease burden.
– Public awareness campaigns and educational materials.
– Access to affordable diagnostic tests and antiviral treatments.
– Collaboration and coordination between different stakeholders and organizations.

The strength of evidence for this abstract is 7 out of 10.
The evidence in the abstract is strong, but there are some areas for improvement. The study conducted a systematic review and meta-analysis, which are robust research methods. The authors searched multiple databases and included studies published in any language, which increases the comprehensiveness of the review. They also contacted study authors for clarification and compiled genotypic data. However, there are a few suggestions to improve the evidence. First, the authors could have provided more details on the inclusion and exclusion criteria for the studies included in the review. This would help readers assess the quality and relevance of the included studies. Second, the authors could have discussed the limitations of their review, such as potential biases or heterogeneity among the included studies. Finally, the authors could have provided more information on the risk of bias assessment and the results of the publication bias assessment. These additional details would enhance the transparency and reliability of the evidence.

Background Hepatitis D virus (also known as hepatitis delta virus) can establish a persistent infection in people with chronic hepatitis B, leading to accelerated progression of liver disease. In sub-Saharan Africa, where HBsAg prevalence is higher than 8%, hepatitis D virus might represent an important additive cause of chronic liver disease. We aimed to establish the prevalence of hepatitis D virus among HBsAg-positive populations in sub-Saharan Africa. Methods We systematically reviewed studies of hepatitis D virus prevalence among HBsAg-positive populations in sub-Saharan Africa. We searched PubMed, Embase, and Scopus for papers published between Jan 1, 1995, and Aug 30, 2016, in which patient selection criteria and geographical setting were described. Search strings included sub-Saharan Africa, the countries therein, and permutations of hepatitis D virus. Cohort data were also added from HIV-positive populations in Malawi and Ghana. Populations undergoing assessment in liver disease clinics and those sampled from other populations (defined as general populations) were analysed. We did a meta-analysis with a DerSimonian-Laird random-effects model to calculate a pooled estimate of hepatitis D virus seroprevalence. Findings Of 374 studies identified by our search, 30 were included in our study, only eight of which included detection of hepatitis D virus RNA among anti-hepatitis D virus seropositive participants. In west Africa, the pooled seroprevalence of hepatitis D virus was 7·33% (95% CI 3·55–12·20) in general populations and 9·57% (2·31–20·43) in liver-disease populations. In central Africa, seroprevalence was 25·64% (12·09–42·00) in general populations and 37·77% (12·13–67·54) in liver-disease populations. In east and southern Africa, seroprevalence was 0·05% (0·00–1·78) in general populations. The odds ratio for anti-hepatitis D virus detection among HBsAg-positive patients with liver fibrosis or hepatocellular carcinoma was 5·24 (95% CI 2·74–10·01; p<0·0001) relative to asymptomatic controls. Interpretation Findings suggest localised clusters of hepatitis D virus endemicity across sub-Saharan Africa. Epidemiological data are needed from southern and east Africa, and from patients with established liver disease. Further studies should aim to define the reliability of hepatitis D virus testing methods, identify risk factors for transmission, and characterise the natural history of the infection in the region. Funding Wellcome Trust, Royal Society.

We did a systematic review and meta-analysis of studies of the prevalence of hepatitis D virus in sub-Saharan Africa, including added data for anti-hepatitis D virus and hepatitis D virus RNA prevalence from two HIV-positive cohorts in Ghana and Malawi, where scarce data were previously available. AJS searched PubMed, Embase, and Scopus for studies published in any language between Jan 1, 1995, and Aug 30, 2016, in which the prevalence of anti-hepatitis D virus antibody or hepatitis D virus RNA was reported. Search strings included sub-Saharan Africa, the countries therein, and permutations of hepatitis D virus (appendix). MC and AJS independently assessed articles for inclusion; disagreements were resolved by consensus. Hepatitis D virus seroprevalence was defined as reported detection of anti-hepatitis D virus by enzyme immunoassay in HBsAg-positive patients. To be included in our review, hepatitis D virus seroprevalence, patient selection methods, and the geographical and clinical setting had to be reported in the study.12 Data for infants or children whose age was not described were excluded to avoid confounding from potential maternal antibody transfer. Populations undergoing assessment in liver disease clinics and those sampled from other populations (defined as general populations) were analysed separately. We contacted study authors for clarification as required. Genotypic data were compiled from studies in which hepatitis D virus RNA was sequenced. We also searched the public sequence databases European Nucleotide Archive and GenBank with the same search strategy used in our initial search (appendix). We excluded genotypic data from studies of immigrants from sub-Saharan Africa who now reside outside the region. Our study was done in accordance with PRISMA recommendations.13 AJS extracted seroprevalence data. Duplicate data from the same locations were excluded. Confidence intervals (CIs) were computed by the Wilson method and pooled seroprevalence was calculated with the DerSimonian-Laird random-effects model with Freeman-Tukey double arcsine transformation.14, 15 We chose a random-effects model a priori because we anticipated heterogeneity arising from variation in study geography and populations. To avoid small sample bias in the random-effects model, we excluded studies in which fewer than ten patients underwent RNA testing, for our calculation of the pooled estimate of hepatitis D virus RNA positivity in patients seropositive for hepatitis D virus. Between-study heterogeneity was assessed with the I2 statistic. Seroprevalence in patients with liver disease compared with that in those without liver disease were pooled with a DerSimonian-Laird random-effects model.14 Meta-regression was done with a residual maximum-likelihood model to examine for sources of heterogeneity related to study location, rural versus urban setting, and the effect of HIV infection by comparison with data from cohorts in which the HIV status of recruited participants was known. We did sensitivity analyses to investigate the effect of population source and of using potentially unrepresentative samples. Risk of bias was independently assessed by AJS and MC with a prevalence critical appraisal tool.16 Publication bias was assessed by inspection of a funnel plot and Egger's test.17 Analyses were done with metan, metaprop, and metareg packages in Stata (version 14.2). The study funder had no role in study design; data collection, analysis, or interpretation; or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

The study conducted a systematic review and meta-analysis to determine the prevalence of hepatitis D virus (HDV) in sub-Saharan Africa. The researchers searched for studies published between January 1, 1995, and August 30, 2016, that reported the prevalence of anti-hepatitis D virus antibody or HDV RNA. They included studies that reported HBsAg-positive patients and provided information on patient selection methods, geographical and clinical settings. The study analyzed populations from liver disease clinics and general populations separately. The researchers also contacted study authors for clarification when necessary. They used a random-effects model to calculate pooled seroprevalence and assessed between-study heterogeneity using the I2 statistic. Meta-regression was conducted to examine sources of heterogeneity. Sensitivity analyses were performed to investigate the effect of population source and sample representativeness. Risk of bias was assessed using a prevalence critical appraisal tool, and publication bias was assessed using a funnel plot and Egger’s test. The study was conducted in accordance with PRISMA recommendations, and the funding came from the Wellcome Trust and the Royal Society. The study’s findings suggest localized clusters of HDV endemicity across sub-Saharan Africa, and further research is needed to define testing methods, identify transmission risk factors, and characterize the infection’s natural history in the region.
AI Innovations Description
The provided information describes a systematic review and meta-analysis of the prevalence of hepatitis D virus (HDV) in sub-Saharan Africa. The study aimed to establish the prevalence of HDV among HBsAg-positive populations in the region. The researchers conducted a comprehensive search of studies published between January 1, 1995, and August 30, 2016, in PubMed, Embase, and Scopus. They included studies that reported the prevalence of anti-hepatitis D virus antibody or HDV RNA. The seroprevalence of HDV was calculated using a random-effects model, and meta-regression was performed to examine sources of heterogeneity.

The findings of the study revealed localized clusters of HDV endemicity across sub-Saharan Africa. The seroprevalence of HDV varied among different regions, with higher rates observed in central Africa compared to west Africa. Limited data were available for east and southern Africa. The study also found that HBsAg-positive patients with liver fibrosis or hepatocellular carcinoma had a higher likelihood of detecting anti-hepatitis D virus antibodies.

The study recommends further research to gather epidemiological data from southern and east Africa and from patients with established liver disease. It also suggests the need to define the reliability of HDV testing methods, identify risk factors for transmission, and characterize the natural history of the infection in the region.

In terms of developing an innovation to improve access to maternal health, the findings of this study can inform the development of targeted interventions and strategies to address the prevalence of HDV in sub-Saharan Africa. This could include implementing screening programs for HDV among HBsAg-positive pregnant women, providing access to antiviral treatments, and raising awareness about the risks and prevention of HDV transmission. Additionally, the study highlights the importance of integrating HDV testing and management into existing maternal health programs and services.
AI Innovations Methodology
The provided text describes a systematic review and meta-analysis conducted to determine the prevalence of hepatitis D virus (HDV) in sub-Saharan Africa. The study aimed to establish the prevalence of HDV among HBsAg-positive populations in the region. The methodology involved searching various databases for relevant studies published between January 1, 1995, and August 30, 2016. The search strings included sub-Saharan Africa, countries within the region, and permutations of HDV. The inclusion criteria required studies to report the prevalence of anti-HDV antibody or HDV RNA, patient selection methods, and the geographical and clinical setting. Data from liver disease clinics and general populations were analyzed separately. The authors also contacted study authors for clarification when necessary. The seroprevalence data were extracted, and a meta-analysis was conducted using a random-effects model to calculate pooled estimates of HDV seroprevalence. The study also assessed the odds ratio for HDV detection among HBsAg-positive patients with liver fibrosis or hepatocellular carcinoma compared to asymptomatic controls. Meta-regression was performed to examine sources of heterogeneity, and sensitivity analyses were conducted to investigate the effect of population source and sample representativeness. Risk of bias was assessed, and publication bias was evaluated. The study was conducted in accordance with PRISMA recommendations, and the funding source had no role in the study design, data collection, analysis, interpretation, or writing of the report. The corresponding author had full access to the data and final responsibility for the decision to submit for publication.

Statistics:
Citations: 77
Authors: 9
Identifiers:
DOI: 10.1016/S2214-109X(17)30298-X
Research Areas:
Cancer, Disparities, Genetics and Genomics, Health System and Policy, Infectious Diseases, Maternal and Child Health
Study Countries:
Ghana, Malawi, Multi-Countries
Study Design:
Case-Control Study, Cohort Study, Cross Sectional Study, Grounded Theory
Study Approach:
Mixed-methods, Quantitative, Systematic Review
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