Changes in Bile Acids and Microbiota in Patients With Hepatitis D Treated With Bulvertide

Changes in Bile Acid Profile and Gut Microbiota in Patients Undergoing Treatment With Bulevirtide for Hepatitis Delta Virus Infection

HDV is an RNA virus that infects only in the presence of HBV, affecting about 13% of HBsAg carriers. In Italy, prevalence ranges from 3.2% to 9.3%. It increases the risk of cirrhosis, fulminant hepatitis, and HCC, particularly in high-risk groups (HIV, HCV, drug users, dialysis patients). Until 2020, pegIFN was the only therapy; since 2022, bulevirtide (BLV) has been available, blocking viral entry into hepatocytes and reducing HDV RNA and liver stiffness, with efficacy in 45-48% of patients, though the optimal treatment duration remains uncertain. The gut microbiota and bile acids also play a role in fibrosis and cirrhosis progression: dysbiosis, typical in cirrhotic patients, alters bile acid metabolism and increases intrahepatic toxicity.

Inclusion Criteria:

• Patients with chronic HDV-related hepatitis or compensated liver cirrhosis (Child-Pugh class A)
• Positive HDV RNA within the 24 weeks prior to enrollment
• Ongoing antiviral therapy for HBV at the time of enrollment
• First prescription of Bulevirtide 2 mg issued within 30 days prior to enrollment
• Caucasian ethnicity
• Age ≥18 years
• Normocaloric omnivorous diet
• No intake of antibiotics, probiotics, or prebiotics in the month prior to enrollment
• Signed informed consent

Exclusion Criteria:

• Decompensated liver cirrhosis (Child-Pugh Score B or C)
• Patients without HBV-HDV-related infection/hepatitis/cirrhosis
• Age ≤18 years
• Pregnant or breastfeeding women
• Concomitant diseases with short life expectancy (solid or hematologic neoplasms, heart failure NYHA III/IV, COPD GOLD C-D)
• Conditions (celiac disease, chronic inflammatory bowel diseases) or use of medications (antibiotics, probiotics, prebiotics) capable of altering gut microbiota composition