_Background_ Hepatitis delta virus (HDV) coinfects with hepatitis B virus (HBV) causing the most severe form of viral hepatitis. However, its exact global disease burden remains largely obscure. We aim to establish the global epidemiology, infection mode-stratified disease progression, and clinical outcome of HDV infection. 
_Methods_ We conducted a meta-analysis with a random-effects model and performed data synthesis. 
_Results_ The pooled prevalence of HDV is 0.80% (95% confidence interval [CI], 0.63–1.00) among the general population and 13.02% (95% CI, 11.96–14.11) among HBV carriers, corresponding to 48–60 million infections globally. Among HBV patients with fulminant hepatitis, cirrhosis, or hepatocellular carcinoma, HDV prevalence is 26.75% (95% CI, 19.84–34.29), 25.77% (95% CI, 20.62–31.27), and 19.80% (95% CI, 10.97–30.45), respectively. The odds ratio (OR) of HDV infection among HBV patients with chronic liver disease compared with asymptomatic controls is 4.55 (95% CI, 3.65–5.67). Hepatitis delta virus-coinfected patients are more likely to develop cirrhosis than HBV-monoinfected patients with OR of 3.84 (95% CI, 1.79–8.24). Overall, HDV infection progresses to cirrhosis within 5 years and to hepatocellular carcinoma within 10 years, on average. 
_Conclusions_ Findings suggest that HDV poses a heavy global burden with rapid progression to severe liver diseases, urging effective strategies for screening, prevention, and treatment.

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Estimating the Global Prevalence, Disease Progression, and Clinical Outcome of Hepatitis Delta Virus Infection.

Approximately 5% of individuals infected with hepatitis B virus (HBV) are coinfected with hepatitis D virus (HDV). Chronic HBV/HDV coinfection is associated with an unfavourable outcome, with many patients developing liver cirrhosis, liver failure and eventually hepatocellular carcinoma within 5–10 years. The identification of the HBV/HDV receptor and the development of novel in vitro and animal infection models allowed a more detailed study of the HDV life cycle in recent years, facilitating the development of specific antiviral drugs. The characterisation of HDV-specific CD4+ and CD8+T cell epitopes in untreated and treated patients also permitted a more precise understanding of HDV immunobiology and possibly paves the way for immunotherapeutic strategies to support upcoming specific therapies targeting viral or host factors. Pegylated interferon-α has been used for treating HDV patients for the last 30 years with only limited sustained responses. Here we describe novel treatment options with regard to their mode of action and their clinical effectiveness. Of those, the entry-inhibitor bulevirtide (formerly known as myrcludex B) received conditional marketing authorisation in the European Union (EU) in 2020 (Hepcludex). One additional drug, the prenylation inhibitor lonafarnib, is currently under investigation in phase III clinical trials. Other treatment strategies aim at targeting hepatitis B surface antigen, including the nucleic acid polymer REP2139Ca. These recent advances in HDV virology, immunology and treatment are important steps to make HDV a less difficult-to-treat virus and will be discussed.

https://gut.bmj.com/content/gutjnl/early/2021/06/07/gutjnl-2020-323888.full.pdf

Hepatitis D virus in 2021: virology, immunology and new treatment approaches for a difficult-to-treat disease.

Among adults in the 2011-2016 National Health and Nutrition Examination Survey (NHANES), the estimated prevalence of hepatitis B surface antigen (HBsAg) was 0.36% overall and 3.4% in non-Hispanic Asians. Among adult HBsAg carriers, 42% had antibodies to hepatitis delta virus (anti-HDV). Routine anti-HDV testing should be considered for HBsAg carriers.

/pdf/prevalence-of-hepatitis-b-and-hepatitis-d-virus-infections-14qn1crj6i.pdf

Prevalence of Hepatitis B and Hepatitis D Virus Infections in the United States, 2011-2016.

Chronic hepatitis D and hepatocellular carcinoma: A systematic review and meta-analysis of observational studies

Viral Hepatitis: Etiology, Epidemiology, Transmission, Diagnostics, Treatment, and Prevention.

Objective Hepatitis D virus (HDV) is a defective virus that completes its life cycle only with hepatitis B virus (HBV). The HBV with HDV super-infection has been considered as one of the most severe forms of the chronic viral hepatitis. However, there is a scarcity of data on the global burden of HDV infection. Design We searched PubMed, Embase, Cochrane Library and China Knowledge Resource Integrated databases from 1 January 1977 to 31 December 2016. We included studies with a minimum sample size of 50 patients. Our study analysed data from a total of 40 million individuals to estimate the prevalence of HDV by using Der-Simonian Laird random-effects model. The data were further categorised according to risk factors. Results From a total of 2717 initially identified studies, only 182 articles from 61 countries and regions met the final inclusion criteria. The overall prevalence of HDV was 0.98% (95% CI 0.61 to 1.42). In HBsAg-positive population, HDV pooled prevalence was 14.57% (95% CI 12.93 to 16.27): Seroprevalence was 10.58% (95% CI 9.14 to 12.11) in mixed population without risk factors of intravenous drug use (IVDU) and high-risk sexual behaviour (HRSB). It was 37.57% (95% CI 29.30 to 46.20) in the IVDU population and 17.01% (95% CI 10.69 to 24.34) in HRSB population. Conclusion We found that approximately 10.58% HBsAg carriers (without IVDU and HRSB) were coinfected with HDV, which is twofold of what has been estimated before. We also noted a substantially higher HDV prevalence in the IVDU and HRSB population. Our study highlights the need for increased focus on the routine HDV screening and rigorous implementation of HBV vaccine programme.

https://gut.bmj.com/content/gutjnl/early/2018/09/18/gutjnl-2018-316601.full.pdf

Wei-Ming Zhang

Papers

Prevalence and burden of hepatitis D virus infection in the global population: a systematic review and meta-analysis