Hepatitis D-Associated Hospitalizations in the United States: 2010–2018

Paul Wasuwanich; Catherine W. Striley; Saleem Kamili; Eyasu H. Teshale; Eric C. Seaberg; Wikrom Karnsakul


J Viral Hepat. 2022;29(3):218-226. 

In This Article

Abstract and Introduction


In the United States, hepatitis D is not a reportable condition, leading to gaps in epidemiological and clinical knowledge. We aim to estimate the incidence of hepatitis D-associated hospitalizations in the United States and describe the clinical, demographic and geographic characteristics of those hospitalizations. We utilized hospitalization data from the 2010–2018 National Inpatient Sample from the Healthcare Cost and Utilization Project. Hepatitis D and hepatitis B only (HBV only) hospitalizations were identified by International Classification of Diseases, Ninth Revision (ICD-9) and International Classification of Diseases, Tenth Revision (ICD-10) codes. We identified 3825 hepatitis D-associated hospitalizations. The hospitalization rate of hepatitis D was between 6.9 and 20.7 per 10,000,000 but did not change significantly over time. Compared to HBV only, the hepatitis D cohort had a greater proportion of males, Hispanics, hospitalizations in the Northeast region. The hepatitis D-associated hospitalizations also had significantly greater frequencies of liver failure, non-alcoholic cirrhosis, portal hypertension, ascites and thrombocytopenia. While mortality in hepatitis D was similar to that of HBV only, age >65 years (odds ratio [OR] = 3.79; p = .020) and having a diagnosis of alcoholic cirrhosis (OR = 3.37; p = .044) increased the odds of mortality within the hepatitis D cohort. Although the hepatitis D-associated hospitalizations were relatively uncommon, they were associated with severe complications.


Hepatitis D is a severe viral disease caused by the hepatitis delta virus (HDV), occurring only in populations with a simultaneous hepatitis B virus (HBV) infection. Globally, there are an estimated 291,992,000 individuals with chronic HBV infection.[1] Of those infected with HBV, 4.5%–14.6% are also infected with HDV.[2,3] In the United States, the prevalence of HDV infections among hepatitis B surface antigen (HBsAg)-positive individuals is estimated to be between 5.9% and 7.2%.[2,3] Worldwide, hepatitis D is an important burden of liver disease. Hepatitis D is estimated to be responsible for 18% of cirrhosis and 20% of hepatocellular carcinoma among those with hepatitis B.[2]

Hepatitis delta virus is considered a satellite virus, an extremely rare class among human viruses, requiring HBV in order to propagate.[4] Currently, eight genotypes of HDV have been identified, classified as HDV genotype 1 through 8.[5] In the United States, HDV genotype 1 is the predominant genotype; however, the information about the circulation of other genotypes is lacking, and studies conducted in the past two decades have been limited in number and in geographic range.[6–8] While studies are few, genotype-specific outcomes for hepatitis D have been demonstrated. For instance, patients infected with HDV genotype 5 have been shown to have better prognosis compared to those infected with HDV genotype 1.[9]

Infection by HDV results in severe complications, often causing fulminant hepatitis and causing cirrhosis in 70%–80% of cases.[10] However, risk for HDV infection is not homogenous among the population infected with HBV. The prevalence of hepatitis D is higher in people who inject drugs and in people who are infected with hepatitis C virus (HCV) or human immunodeficiency virus (HIV).[2] However, in pregnant persons and foetuses/neonates, the prevalence of HDV and its burden is not well known, particularly in the United States where hepatitis D is not routinely tested in pregnant persons with HBV and studies on this topic are lacking.[11–13] It is known that in pregnant women with HBV there is an increased risk of preterm delivery,[14] but knowledge of preterm delivery as well as knowledge of maternal and foetal/neonatal mortality in the setting of hepatitis D is sparse.

In 2020, bulevirtide, a drug for the treatment of HDV infection, was conditionally approved by the European Medicines Agency for use in the European Union.[15] With approval for this drug by the U.S. Food and Drug Administration expected to occur in the near future, accurate and up-to-date epidemiological data are needed in order to target high-risk populations for diagnosis and treatment of HDV infection. Thus, we aim to estimate the incidence and describe trends of hepatitis D-associated hospitalizations in the United States as well as describe and analyse the clinical, demographic and geographic characteristics of patients and pregnant persons hospitalized with hepatitis D during the 2010–2015 and 2015–2018 time periods.