Response‐guided long‐term treatment of chronic hepatitis D patients with bulevirtide—results of a “real world” study

• Published in: Alimentary pharmacology & therapeutics 2022-07, Vol.56 (1), p.144-154
• Main Authors: Jachs, Mathias, Schwarz, Caroline, Panzer, Marlene, Binter, Teresa, Aberle, Stephan W., Hartl, Lukas, Dax, Kristina, Aigner, Elmar, Stättermayer, Albert F., Munda, Petra, Graziadei, Ivo, Holzmann, Heidemarie, Trauner, Michael, Zoller, Heinz, Gschwantler, Michael, Mandorfer, Mattias, Reiberger, Thomas, Ferenci, Peter
• Format: Article
• Language: English
• Subjects: Antiviral Agents; Bulevirtide in Chronic Hepatitis D Infection; Cirrhosis; Hepatitis; Hepatitis D, Chronic - drug therapy; Hepatitis delta virus; Hepatitis Delta Virus - genetics; Hepatocytes; Humans; Interferon; Interferon-alpha - therapeutic use; Lipopeptides; Liver cirrhosis; Liver Cirrhosis - drug therapy; Middle Aged; Original; Patients; Ribonucleic acid; RNA; RNA, Viral - genetics; Treatment Outcome
• ISSN: 0269-2813; 1365-2036
• DOI: 10.1111/apt.16945

Summary Background and Aim Bulevirtide (BLV) blocks the uptake of the hepatitis D virus (HDV) into hepatocytes via the sodium/bile acid cotransporter NTCP. BLV was conditionally approved by the EMA but real‐life data on BLV efficacy are limited. Methods Patients were treated with BLV monotherapy. Patients who did not achieve further decreases in HDV‐RNA after 24 weeks were offered PEG‐IFN as an add‐on therapy in a response‐guided manner. Results Twenty‐three patients (m: 10, f: 13; mean age: 47.9 years, cirrhosis: 16; median ALT: 71 IU/ml; median HDV‐RNA: 2.1 × 105copies/ml) started BLV monotherapy (2 mg/day: 22; 10 mg/day: 1). Twenty‐two completed ≥24 weeks of treatment (24–137 weeks): Ten (45%) were classified as BLV responders at week 24. BLV was stopped in two patients with >6 months HDV‐RNA undetectability, but both became HDV‐RNA positive again. One patient was transplanted at week 25. One patient terminated treatment because of side effects at week 60. Ten patients are still on BLV monotherapy. Adding PEG‐IFN in eight patients induced an HDV‐RNA decrease in all (1.29 ± 0.19 [SD] log within 12 weeks). HDV‐RNA decreased by >2log or became undetectable in 45%(10/22), 55%(11/20), 65% (13/20) and 69% (9/13); and ALT levels normalised in 64% (14/22), 85% (17/20), 90% (18/20) and in 92% (12/13) patients at weeks 24, 36, 48 and 60, respectively. Portal pressure decreased in 40% (2/5) of patients undergoing repeated measurement under BLV therapy. Conclusion Long‐term BLV monotherapy is safe and effectively decreases HDV‐RNA and ALT—even in patients with cirrhosis. The optimal duration of BLV treatment alone or in combination with PEG‐IFN remains to be established. An algorithm for a response‐guided BLV treatment approach is proposed. The novel antiviral drug Bulevirtide (BLV) was studied in 23 patients (70% had cirrhosis) with hepatitis D virus infection. At week 24 (W24), 45% (10/22, one dropped out) were classified as virologic responders (2‐log decline or HDV‐RNA undetectablity) to BLV monotherapy. Interferon treatment was added in eight patients who achieved no further decline in HDV‐RNA after W24, inducing a synergistic antiviral effect. The proportion of patients who achieved virologic response and normalisation of ALT continuously increased from W24 to W60. No clinically relevant side effects were attributed to BLV treatment, despite marked increases in bile acid levels.