Clinical and laboratory parameters correlated to HDV undetectability after 48 weeks of bulevirtide

Hepatitis Delta Virus (HDV) is a small RNA virus that can cause a severe chronic hepatitis in patients already infected with Hepatitis B virus (HBV). HDV co-infection is a risk factor for cirrhosis and hepatocellular carcinoma (HCC) development. For a long time, there was no effective treatment for HDV hepatitis. On January 2023 bulevirtide (BLV) was approved in Italy as the first therapeutic option for HDV infection. The undetectability of HDV-RNA is an end-point of the treatment. Despite the observation of a good clinical and laboratory response, the identification of parameters to predict a more rapid and durable response to therapy remains uncertain. The aim of this study is to analyze which parameters can be predictive of undetectable HDV-RNA during BLV treatment. We analyzed intrahepatic and peripheral virological parameters, ALT, information on cirrhosis status, combined response at 12 and 24 weeks from seven patients of our cohort of HDV patients from Policlinico Tor Vergata of Rome, who received BLV at least for 48 weeks by March 2025. Droplet digital PCR was used to quantify intrahepatic HBV and HDV markers. Combined response was defined as the achievement of >2 log HDV-RNA or undetectable HDV-RNA along with ALT normalization. HDV-RNA <22 copies/ml was the lower limit of quantification (LLoQ). HDV-RNA was defined undetectable when it was below the LLoQ (22IU/ml). Seven patients, all virologically suppressed under nucleos(t)ide analogues (NUC), received BLV for 48 weeks. Median [IQR] age was 47 (44–55) years. 1 patient was Italian, 5 from Eastern-Europe, 1 from Togo. At baseline, median (IQR) serum HDV-RNA and HBsAg were 5.9 (4.8–7.1) and 4.1 (3.8–4.4) log IU/ml, respectively. Median (IQR) ALT was 91 (47–118) U/l while Ishak score was 5 for five patients, 4 and 3 for the remaining two. Intrahepatic median (IQR) HDV-RNA was 3563 (1777–9045) copies/1000cells (table 1). Three patients received Peg-Interferon-alfa but discontinued after 2, 4 and 8 weeks respectively for adverse effects