Treat hepatitis D earlier? New AASLD guidance expands screening and antiviral use

Clinical takeaway: Test all patients who are hepatitis B surface antigen positive for hepatitis delta virus (HDV) at least once, regardless of risk factors. Adults with chronic HDV viremia and compensated liver disease, including compensated cirrhosis, should generally be considered for HDV-specific treatment, with bulevirtide now positioned as a preferred therapy.

The American Association for the Study of Liver Diseases (AASLD) has issued a new expert-based practice opinion (EXPO) on the diagnosis and management of HDV infection, a severe form of viral hepatitis that accelerates progression to cirrhosis, liver failure, hepatocellular carcinoma, and death. The document was developed to provide practical guidance in a rapidly evolving field, particularly following the arrival of new antiviral treatment options.

A major recommendation is universal HDV screening among patients who test positive for hepatitis B surface antigen (HBsAg). The authors recommend at least one HDV antibody test for all HBsAg-positive individuals, followed by HDV RNA testing to confirm active infection in those with positive antibody results. The guidance also encourages reflex testing and, where feasible, double-reflex testing that automatically adds HDV RNA testing after a positive antibody result.

For patients with confirmed chronic HDV infection, the document recommends liver fibrosis assessment, preferably with elastography, along with ongoing monitoring of liver enzymes, HDV RNA, HBV DNA, and fibrosis progression. Adults with chronic HDV should also undergo hepatocellular carcinoma surveillance with ultrasound and alpha-fetoprotein testing every 6 months.

The most notable treatment update is the broad recommendation to consider antiviral therapy for all adults with chronic HDV viremia and compensated liver disease, regardless of ALT levels. For patients seeking a finite treatment course and without contraindications to interferon, the authors suggest bulevirtide 8.5 mg daily combined with pegylated interferon alfa-2a for 48 weeks, followed by bulevirtide alone to complete 96 weeks of therapy.

For patients unwilling or unable to take interferon, bulevirtide monotherapy is the preferred option, with treatment generally continued long term while virologic response is maintained. Pegylated interferon alfa-2a remains an alternative for patients who lack access to bulevirtide and for pediatric patients.

The opinion also recommends nucleos(t)ide analogue therapy when cirrhosis, decompensated liver disease, or HBV DNA levels above 2,000 IU/mL are present. Patients should be counseled to avoid alcohol and address metabolic risk factors that may accelerate liver injury.

“HDV has historically been challenging to diagnose and manage, but recent advances in screening and antiviral therapy are changing the treatment landscape,” said Joseph K. Lim, MD. “This publication provides clinicians with a practical framework for identifying patients with HDV, evaluating their disease and making informed treatment decisions based on the best available evidence and expert consensus.”

Key Recommendations

• Test all HBsAg-positive individuals for HDV at least once.
• Confirm active infection with quantitative HDV RNA testing after a positive HDV antibody result.
• Perform fibrosis staging, preferably with elastography, and monitor disease progression regularly.
• Conduct hepatocellular carcinoma surveillance every 6 months in adults with chronic HDV infection.
• Consider HDV-specific antiviral therapy for all adults with chronic HDV viremia and compensated liver disease.
• Use bulevirtide-based therapy as a preferred treatment strategy, with or without pegylated interferon alfa-2a depending on patient goals and eligibility.

Source: Lim JK, et al. (2026 Nov 6) Hepatology. AASLD EXPO: Diagnosis and Management of Hepatitis Delta Virus (HDV) Infection