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While it is difficult to gather a global prevalence of hepatitis delta virus (HDV), a new analysis shows that while rates are relatively low in Japan, co-infections between HDV and hepatitis B virus (HBV) result in a greater likelihood of negative liver outcomes.¹

A team, led by Takashi Sasaki, Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, attempted to identify the prevalence of HBV and HDV co-infections in Japan and followed outcomes for liver fibrosis.

HDV

HDV is a defective, single stranded RNA virus that requires hepatitis B surface antigen (HBsAg) envelop for assembly and transmission. The virus was first discovered in Italy in 1977. Infections can occur simultaneously with hepatitis B virus infections or in chronic carriers of HBsAg. While the hepatitis B vaccine protects against de-novo infections with both viruses, it does not protect chronic HBV carries against superinfections with hepatitis delta virus.

While there is a lot of concern over co-infections of HDV and HBV, the global prevalence of HDV is largely unknown because of insufficient data from many countries. For example, the prevalence of the disease has not been updated in Japan in over 20 years.

The Study

In the study, the investigators screened 1264 consecutive patients with HBV infections at the Hokkaido University Hospital between 2006-2022, 601 of which were included in the final analysis.

The investigators preserved patient serums and tested them for HDV-antibody—immunoglobulin-G.

They also collected and analyzed all the available clinical information and compared the changes in liver fibrosis using the fibrosis-4 (FIB-4) index between propensity-matched patients with and without the evidence of anti-HDV antibodies. This was corrected for baseline FIB-4 index, nucleus(t)ide-analog administration, alcohol intake, sex, human-immunodeficiency-virus co-infection, liver cirrhosis and age.

The results show 1.7% (n = 10) of patients had detectable anti-HDV antibodies and this group had a significantly higher prevalence of liver cirrhosis, significantly lower prothrombin time, and a higher prevalence of HIV co-infection compared to patients who demonstrated serum anti-HDV antibody negatively.

In the propensity-matched longitudinal analysis, the investigators found liver fibrosis (FIB-4 index) progressed more rapidly in patients with positive results for anti-HDV antibody tests.

“The recent prevalence of HDV infections in Japanese patients with HBV was 1.7%,” the authors wrote. “These patients experienced rapid liver fibrosis progression, highlighting the importance of routine HDV testing.”

HDV Declining in Italy

HBV vaccination is contributing to a precipitous drop in acute Delta virus hepatitis (HDV) in Italy over the last 3 decades, potentially because of a public health campaign.²

A team, led by Tommaso Stroffolini, Department of Tropical and Infectious Diseases, Policlinico Umberto I, evaluated incidence of and risk factors associated with acute Delta virus hepatitis in Italy following the introduction of the compulsory vaccination against hepatitis B virus in 1991.

The overall incidence of acute HDV per 1 million inhabitants declined between 1987-2019, from 3.2 cases to 0.04 cases. This was parallel to numbers found in HBV per 100,000 people, which declined from 10.0 to 0.39 in the same time period.

However, the age of the patient population infected by the virus did increase during the course of the study. Between 1991-1999 the median age of a patient was 27 years, while between 2010-2019 the median age of patients was 44 years (P <0.001).

Other trends identified include a decrease in the male to female ratio, which decreased from 3.8 to 2.1, the proportion of coinfections increased from 55-75% (P = 0.003), and HBsAg positive acute hepatitis testing by IgM anti-HDV linearly decreased from 50.1% to 34.1% (P <0.001).