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.