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

Patients with chronic hepatitis or compensated liver cirrhosis (Child-Pugh Score A) related to HBV-HDV, at the time of the first prescription of BLV 2 mg, will be enrolled.