The global prevalence of hepatitis D virus infection: Systematic review and meta-analysis

Abstract

Background and aims: There are uncertainties about the epidemic patterns of HDV infection and its contribution to the burden of liver disease. We estimated the global prevalence of HDV infection and explored its contribution to the development of cirrhosis and hepatocellular carcinoma (HCC) among HBsAg-positive people.

Methods: We searched Pubmed, EMBASE and Scopus for studies reporting on total or IgG anti-HDV among HBsAg-positive people. Anti-HDV prevalence was estimated using a binomial mixed model, weighting for study quality and population size. The population attributable fraction (PAF) of HDV to cirrhosis and HCC among HBsAg-positive people was estimated using random effects models.

Results: We included 282 studies, comprising 376 population samples from 95 countries, which together tested 120,293 HBsAg-positive people for anti-HDV. The estimated anti-HDV prevalence was 4.5% (95% CI 3.6-5.7) among all HBsAg-positive people and 16.4% (14.6-18.6) among those attending hepatology clinics. Worldwide, 0.16% (0.11-0.25) of the general population, totalling 12.0 (8.7-18.7) million people, were estimated to be anti-HDV positive. Prevalence among HBsAg-positive people was highest in Mongolia, the Republic of Moldova and countries in Western and Middle Africa, and was higher in injecting drug users, haemodialysis recipients, men who have sex with men, commercial sex workers, and those with HCV or HIV. Among HBsAg-positive people, preliminary PAF estimates of HDV were 18% (10-26) for cirrhosis and 20% (8-33) for HCC.

Conclusions: An estimated 12 million people worldwide have experienced HDV infection, with higher prevalence in certain geographic areas and populations. HDV is a significant contributor to HBV-associated liver disease. More quality data are needed to improve the precision of burden estimates.

Lay summary: We combined all available studies to estimate how many people with hepatitis B also have hepatitis D, a viral infection that only affects people with hepatitis B. About 1 in 22 people with hepatitis B also have hepatitis D, increasing to 1 in 6 when considering people with liver disease. Hepatitis D may cause about 1 in 6 of the cases of cirrhosis and 1 in 5 of the cases of liver cancer that occur in people with hepatitis B. Hepatitis D is an important contributor to the global burden of liver disease.

Keywords: Carcinoma; Epidemiology; Hepatitis B; Hepatitis D; Hepatitis delta virus; Hepatocellular; Liver cirrhosis; Meta-analysis; Prevalence.

Graphical abstract

Fig. 1

Selection of studies for inclusion in systematic review of global HDV epidemiology.

Fig. 2

Distribution of included samples by population category and WHO region^a. ^aSelected population groups comprised people who inject drugs, haemodialysis recipients, men who have sex with men, commercial sex workers, and people with hepatitis C virus or HIV. In sub-Saharan Africa countries with adult HIV prevalence >1%, HIV populations were included in the general population. Isolated populations were selected sample populations that were considered not representative of the general population. WHO, World Health Organisation; AFR, African Region; EMR, Eastern Mediterranean Region; EUR, European Region; AMR, Region of the Americas; SEAR, South-East Asian Region; WPR, Western Pacific Region.

Fig. 3

Anti-HDV prevalence in HBsAg-positive people. (A) General populations; (B) Hepatology clinic populations. Each point represents a sample. Point size indicates sample size and colour indicates HDV seroprevalence.

Fig. 4

Country-level estimates of anti-HDV prevalence among HBsAg-positive people. (A) General populations; (B) Hepatology clinic populations. Colour indicates HDV seroprevalence.

Fig. 6

Geographic distribution of HDV genotypes^a. ^aEach circle represents a unique sample with area proportional to sample size aGenotype data identified by searches and from publicly available HDV sequences deposited in GenBank (https://www.ncbi.nlm.nih.gov/genbank/) and European Nucleotide Archive Database (http://www.ebi.ac.uk/ena).

Fig. 5

HDV seroprevalence among selected population groups relative to general populations or asymptomatic HBsAg-positive people from the same geographic region^a. ^aComparators are general population or asymptomatic HBsAg-positive samples from the same geographic region. Odds ratios were pooled using a random effects model. Diamonds indicate central estimate and 95% CI for pooled odds ratios for each population group. I² represents the proportion of variability that can be attributed to heterogeneity. τ² represents an estimate of between-study variance, for each group.