Table 4.
Results of Bulevirtide (BLV) therapy both in monotherapy and in combination therapy with PegIFNalpha derived from real life studies.
| Authors, year, (reference) | Treatment | Study design | Sample size | Treatment length | Age, Liver disease | Primary outcome | Percentage of subjects with HDV RNA undetectable data | Biochemical outcome | Combined response | Serious adverse events % - discontinuations % |
|---|---|---|---|---|---|---|---|---|---|---|
| de Lédinghen et al., 2021 (https://www.natap.org/2021/AASLD/AASLD_18.htm) | BLV 2mg/BLV +pegIFNa | Prospective, observational | 77 monotherapy /68 +pegIFNa |
12 months | 41.6 med in mono group, 40.8 med in combo group. Compensated cirrhosis, adv fibrosis, F2 with ALT >2nv for 6 mnt |
HDV RNA neg or >2log decrease at 12mnt: 68.3% BLV/93.9% BLV+INF | Monotherapy: 68.3%; combination: 85% | ALT neg at 12mnt 48.8% BLV/36.4% BLV+INF | 39.0% BLV/30.3% BLV+INF | Grade 3-4 9%-8.8% discontinuations 2.6%-4.4% |
| (
Jachs et al., 2022
) |
BLV 2mg/day; BLV 10mg/day. In lack of response at week 24, pegIFNa was added | Observational, retrospective | 22/1 | 24-137 weeks | mean age: 47.9 years. 5 pts over 65 Compensated cirrhosis: 70% |
HDV‐RNA decreased by >2log or undetectable in 45%, 55% 65% and 69% at 24, 36, 48 and 60 wks. 2 relapses in patients terminating treatment at >24 wks undetectable | Not specified | Normalization of ALT level: 64%, 85%, 90% and in 92% at 24, 36, 48 and 60 wks | 32%, 50%, 60% 62% at 24, 36, 48 and 60 wks | 1 pt needed growth factor for wbc count 4.3% - 0% |
| (
Jachs et al., 2022
) |
BLV 2mg/day In lack of response at week 24, pegIFNa was added | Observational, prospective | 7 | 46–141 weeks | Age range: 31 to 68 years; 1 pt over 65 Compensated cirrhosis: 57,1% |
Study on suspension post undetectability; all patient undetectable: 4 relapses in BLV monotherapy, 1 patient no relapse in BLV monotherapy, 2 received pegIFN adjunction: no relapse |
1 patient in BLV monotherapy; 2 patients receiving PEGIFN adjunction |
Normalization of ALT level: 42.8%. 1 pt among relapses showed ALT relapse | / | 28.6% - 28.6% (2 pts discontinued pegIFNa) |
| Fontaine et al., 2022 (https://www.natap.org/2022/EASL/EASL_44.htm) | BLV 2mg monotherapy vs BLV 2mg + pegINF | Prospective, observational | 65 monotherapy/50 combination | 48 weeks | 43yo +/- 11/40.5yo +/- 10.9; cirrhotic 58.5%/52.% | Combined outcome (ALT negativization, HDV RNA at least 2 log decline) Monotherapy: at week 24: 17% Combination at week 24: 34% |
Monotherapy: at week 24: 8% Combination at week 24: 44% |
Normalization of ALT level at 24 weeks; monotherapy: 54% Combination: 35% |
Monotherapy: at week 24: 17% Combination at week 24: 34% |
At week 24: monotherapy: 14, combination 18 – monotherapy: 1, combination: 3. |
| (
Comandini et al., 2023
) |
BLV 2mg | Prospective, observational | 13 | 11 months, median | 42 years [IQR 48–62], 2 pt over 65. Compensated cirrhosis | 40% undetectable at 9mnt, 40% rebound at 6-9mnt | 40% undetectable at 9 months | ALT reduction at 9 months 68,5% | At 6 months, 66% w/o HIV, 60% with HIV | 0% - 0% |
| (
Comandini et al., 2023
) |
BLV 2mg/day | Retrospective, observational, multicentric | 114 | 24 weeks | Median: 47 ± 11 52% cirrhotic patient, 4.38% decompensated |
HDV RNA > 2 log decrease or undetectable during follow up (38 ± 17.6 weeks): 76.3% | 21.9% | ALT normalization at 12 weeks: 34.6%; at 24 weeks: 19.2% | undescribed | 0% - 5.2% |
| (
Sandmann et al., 2023
) |
BLV, unspecified dosage | Observational, retrospective | 16 | 6 months | [Age unreported] Compensated cirrhosis: 43.8% |
Decline > 2log HDV RNA: 38% | Not evaluated | Normalization of ALT level: 69% | 37.5% | / |
| (
Degasperi et al., 2022
) |
BLV 2mg/day | Observational | 18 | 48 weeks | Median age: 48 [29-77] Compensated cirrhosis 100% |
At least decline > 2log HDV RNA: 78% | 23% | Normalization of ALT level: 83% | 67% | 0% - 0% |
| (
Degasperi et al., 2022
) |
BLV 2mg/day | Observational | 9 | 48 weeks | 46 years [IQR 41–62] (no over 65 pt) F2 (2 pts), F3 (3 pts), F4 Child A (4pts) |
HDV RNA > 2 log decrease or undetectable at 48 weeks: 85,7% | 3/8 (37.5%) at 48 weeks, | ALT normalization at 48 weeks: 28,5% (all reduced, 2 started from normal values, 1 stopped) | 20% (2 had already neg ALT, 1 had already undetectable RNA) | 0% - 0% |
| ( Degasperi et al., 2022 ) | BLV 2mg/day | Observational, prospective | 7 (3) | 24 weeks (48 weeks) | Median age: 41 ± 8.1 years Compensated cirrhosis: 57.1% |
At least decline > 2log HDV RNA:71.4% (24 weeks)/66% (48 weeks), 1 virologic breakthrough | Not evaluated | Normalization of ALT level: 50% (24 weeks)/66%, 1 re-increase (48 months) | 50% (24 weeks), 66% (48 weeks) | 0% - 0% |
| ( Degasperi et al., 2022 ) | BLV 2mg/day | Observational, retrospective | 93 | 72 weeks | Median age 52 years, 100% cirrhosis, 55% varices, 22% previous ascites | at weeks 24, 48 72, HDV RNA ≥2 Log decline: 67%, 77% 75% | 10%, 16%, 38% at weeks 24, 48 72, respectively | ALT normalization at weeks 24, 48 72 in 67%, 67%, 81% | at weeks 24, 48 72: 45%, 56%, 63% | 0% - 0% |
| Degasperi et al., 2022 ) | BLV 2mg/day | Retrospective, observational, multicentric | 15 | 23 weeks | 100% cirrhosis, 66% previous ascites | decline in HDV-RNA levels by ≥2 log: 66% | Not evaluated | ALT normalization: 47% | unreported | unreported |
| ( Degasperi et al., 2022 ) | BLV 2mg/day | Retrospective, observational, multicentric | 176 | Median 48, up to 96 weeks | 100% cirrhosis, 46% esophageal varices, 12% previous ascites, 6% active HCC Age 50 (19–82) |
at weeks 24, 48, 96, HDV RNA ≥2 Log decline: 48%, 66% and 77% undetectable in 16%, 33%, and 43% |
16%, 33%, and 43% at weeks 24, 48, 96, respectively | at weeks 24, 48, 96, ALT normalization 60%, 69% and 73% | at weeks 24, 48, 96: 28%, 48% and 58% | 0% - 1 pt |
§ End of Treatment; *Bulevirtide; **Tenofovir Disoproxil; ***Pegylated Interferon alpha
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