Poor Hepatitis D Screening in HBV Patients Impacts Survival Outcomes

A new study suggested screening for hepatitis D virus (HDV) is suboptimal, and treatment of hepatitis B infection (HBV) in coinfected individuals could improve survival outcomes.¹

“We found that a minority of individuals with HBV infection are tested for HDV coinfection, and though the proportion of individuals with HDV coinfection is low among those tested, the all-cause mortality is higher among HDV-infected individuals who were not treated for HBV,” wrote investigators, led by Adeel A. Butt, MBBS, FACP, FIDSA, from VA Pittsburgh Healthcare System and Weill Cornell Medicine.

As of now, there are no FDA-approved drugs for HDV, and these patients turn to pegylated interferon and a novel synthetic lipopeptide bulevirtide which have mixed results.² Patients may have reduced HDV RNA levels but then face a virological rebound.

Guidelines recommend screening all HBV-infected individuals for HDV coinfection, but how does comorbid HDV in HBV impact a patient’s survival?¹ Investigators aimed to assess HDV testing rates, coinfection prevalence, and the impact of HDV on all-cause mortality among individuals with HBV.

The primary objective was to determine how many individuals with HBV were tested for HDV, and of those, how many tested positive for HDV. Secondary outcomes included the proportion of individuals referred to a gastroenterologist, hepatologist, or infectious disease specialist following an HBV diagnosis, as well as the proportion prescribed ≥ 3 months of approved medication. The team also compared all-cause mortality rates among individuals with HBV alone and those coinfected with HDV, stratifying by HBV treatment status.

Investigators identified participants with HBV infection through the US Department of Veterans Affairs (VA) healthcare system’s national database. The study included 44,951 individuals who had ≥ 1 positive HBsAg, HBeAg or HBV DNA test.

Among the sample, only a small proportion (13.3%) of individuals with HBV were screened for HDV and 3% of those who were screened tested positive for HDV. More than half of the sample (62.9%) were referred to a gastroenterologist, hepatologist, or infectious disease specialist after their HBV diagnosis.

In total, 40.5% of HDV-coinfected participants and 41.9% of HDV-uninfected participants had a prescription for an HBV medication.

HDV coinfection was associated with a greater all-cause mortality rate per 100 person-years (5.15 for untreated HBV, 3.0 for treated HBV; P = .02) compared to those without HDV coinfection (2.98 for untreated HBV, 2.53 for treated HBV; P < .001). Similarly, Kaplan-Meier curves showed significantly greater mortality among HDV-coinfected individuals who were not treated for HBV (P < .0001).

The study revealed screening rates for HDV among HBV-infected individuals are suboptimal.

“Crude extrapolation of the coinfection rate suggests that an additional approximately 1170 individuals with HDV coinfection may have been missed,” investigators wrote. “Though the reason for a lack of screening is unclear, even those with the highest risk (e.g., Asian/Asian Americans) had very low rate of screening.”

The team added how screening may have been affected since about 1-fifth of individuals had cirrhosis at the time of screening.

Investigators highlighted multiple limitations, including the retrospective study design, no randomization, and a strong male dominance in the study.

“Our data suggest that HBV treatment may blunt or even negate the excess all-cause mortality related to HDV coinfection,” investigators wrote. “Although this observation needs further evaluation and confirmation through randomized clinical trials or larger database studies, HBV treatment is well tolerated with minimal risk of significant adverse events. Therefore, it is prudent to suggest that HBV treatment may mitigate some of the excess risk for adverse outcomes in these high-risk patients while awaiting HDV therapeutic agents.”

References

1. ^{Butt AA, Yan P, Iwnetu R, et al. Hepatitis Delta Coinfection Rates and All-Cause Mortality Among Hepatitis B-Infected Veterans in the USA. J Viral Hepat. Published online October 9, 2024. doi:10.1111/jvh.14021}
2. ^{C. Pan, R. Gish, I. M. Jacobson, K. Q. Hu, H. Wedemeyer, and P. Martin, Diagnosis and Management of Hepatitis Delta Virus Infection. Digestive Diseases and Sciences 68, no. 8 (2023): 3237–3248.}