Abstract
Short-term administration of the entry inhibitor myrcludex-B (MyrB) has been shown to be safe and effective in phase II studies in patients coinfected with hepatitis B virus (HBV) and hepatitis delta virus (HDV). However, its effectiveness and safety are unknown during long-term and high-dose treatment of patients with compensated cirrhosis in real-life settings. Herein, we describe the first 3 European patients with HDV-related compensated cirrhosis who were treated with MyrB 10 mg/day for 48 weeks as a compassionate therapy. Liver function tests, bile acids, and virological markers were monitored every 4 weeks. HBV/HDV-specific T cell quantity (up to 48 and 36 weeks) and HBV RNA levels were also assessed in 2 cases. During MyrB treatment, HDV RNA levels progressively declined from 4.4 and 5.6 logs IU/ml to undetectability in 2 cases, and from 6.8 log copies/ml to 500 copies/ml for the other patient. Alanine aminotransferase normalised after 20, 12 and 28 weeks, respectively. A significant improvement in features of portal hypertension, liver function tests and alpha-fetoprotein levels were documented in 2 cases. In the male patient with histological and clinical stigmata of autoimmune hepatitis, IgG and immunoglobulins rapidly normalised. No significant changes in HBV surface antigen levels and circulating HBV/HDV-specific T cells were demonstrated; HBV DNA and HBV RNA levels remained undetectable throughout the study period. MyrB was well tolerated; patients remained fully asymptomatic despite a significant increase of bile acids. In conclusion, this report shows excellent safety and effectiveness of a 48-week course of MyrB 10 mg/day, combined with tenofovir disoproxil fumarate, for the treatment of HDV-related compensated cirrhosis.
| Original language | English |
|---|---|
| Pages (from-to) | 834-839 |
| Journal | Journal of Hepatology |
| Volume | 71 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Jan 1 2019 |
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Keywords
- Bulevirtide
- Coinfection
- Entry inhibitor
- HBV
- HDV
- HDV RNA
- Hepatitis delta
- Myrcludex-B
- NTCP
- T cell
ASJC Scopus subject areas
- Hepatology
Cite this
Excellent safety and effectiveness of high-dose myrcludex-B monotherapy administered for 48 weeks in HDV-related compensated cirrhosis : A case report of 3 patients. / Loglio, Alessandro; Ferenci, Peter; Uceda Renteria, Sara Colonia; Tham, Christine Y.L.; van Bömmel, Florian; Borghi, Marta; Holzmann, Heidemarie; Perbellini, Riccardo; Trombetta, Elena; Giovanelli, Silvia; Greco, Letizia; Porretti, Laura; Prati, Daniele; Ceriotti, Ferruccio; Lunghi, Giovanna; Bertoletti, Antonio; Lampertico, Pietro.
In: Journal of Hepatology, Vol. 71, No. 4, 01.01.2019, p. 834-839.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Excellent safety and effectiveness of high-dose myrcludex-B monotherapy administered for 48 weeks in HDV-related compensated cirrhosis
T2 - A case report of 3 patients
AU - Loglio, Alessandro
AU - Ferenci, Peter
AU - Uceda Renteria, Sara Colonia
AU - Tham, Christine Y.L.
AU - van Bömmel, Florian
AU - Borghi, Marta
AU - Holzmann, Heidemarie
AU - Perbellini, Riccardo
AU - Trombetta, Elena
AU - Giovanelli, Silvia
AU - Greco, Letizia
AU - Porretti, Laura
AU - Prati, Daniele
AU - Ceriotti, Ferruccio
AU - Lunghi, Giovanna
AU - Bertoletti, Antonio
AU - Lampertico, Pietro
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Short-term administration of the entry inhibitor myrcludex-B (MyrB) has been shown to be safe and effective in phase II studies in patients coinfected with hepatitis B virus (HBV) and hepatitis delta virus (HDV). However, its effectiveness and safety are unknown during long-term and high-dose treatment of patients with compensated cirrhosis in real-life settings. Herein, we describe the first 3 European patients with HDV-related compensated cirrhosis who were treated with MyrB 10 mg/day for 48 weeks as a compassionate therapy. Liver function tests, bile acids, and virological markers were monitored every 4 weeks. HBV/HDV-specific T cell quantity (up to 48 and 36 weeks) and HBV RNA levels were also assessed in 2 cases. During MyrB treatment, HDV RNA levels progressively declined from 4.4 and 5.6 logs IU/ml to undetectability in 2 cases, and from 6.8 log copies/ml to 500 copies/ml for the other patient. Alanine aminotransferase normalised after 20, 12 and 28 weeks, respectively. A significant improvement in features of portal hypertension, liver function tests and alpha-fetoprotein levels were documented in 2 cases. In the male patient with histological and clinical stigmata of autoimmune hepatitis, IgG and immunoglobulins rapidly normalised. No significant changes in HBV surface antigen levels and circulating HBV/HDV-specific T cells were demonstrated; HBV DNA and HBV RNA levels remained undetectable throughout the study period. MyrB was well tolerated; patients remained fully asymptomatic despite a significant increase of bile acids. In conclusion, this report shows excellent safety and effectiveness of a 48-week course of MyrB 10 mg/day, combined with tenofovir disoproxil fumarate, for the treatment of HDV-related compensated cirrhosis.
AB - Short-term administration of the entry inhibitor myrcludex-B (MyrB) has been shown to be safe and effective in phase II studies in patients coinfected with hepatitis B virus (HBV) and hepatitis delta virus (HDV). However, its effectiveness and safety are unknown during long-term and high-dose treatment of patients with compensated cirrhosis in real-life settings. Herein, we describe the first 3 European patients with HDV-related compensated cirrhosis who were treated with MyrB 10 mg/day for 48 weeks as a compassionate therapy. Liver function tests, bile acids, and virological markers were monitored every 4 weeks. HBV/HDV-specific T cell quantity (up to 48 and 36 weeks) and HBV RNA levels were also assessed in 2 cases. During MyrB treatment, HDV RNA levels progressively declined from 4.4 and 5.6 logs IU/ml to undetectability in 2 cases, and from 6.8 log copies/ml to 500 copies/ml for the other patient. Alanine aminotransferase normalised after 20, 12 and 28 weeks, respectively. A significant improvement in features of portal hypertension, liver function tests and alpha-fetoprotein levels were documented in 2 cases. In the male patient with histological and clinical stigmata of autoimmune hepatitis, IgG and immunoglobulins rapidly normalised. No significant changes in HBV surface antigen levels and circulating HBV/HDV-specific T cells were demonstrated; HBV DNA and HBV RNA levels remained undetectable throughout the study period. MyrB was well tolerated; patients remained fully asymptomatic despite a significant increase of bile acids. In conclusion, this report shows excellent safety and effectiveness of a 48-week course of MyrB 10 mg/day, combined with tenofovir disoproxil fumarate, for the treatment of HDV-related compensated cirrhosis.
KW - Bulevirtide
KW - Coinfection
KW - Entry inhibitor
KW - HBV
KW - HDV
KW - HDV RNA
KW - Hepatitis delta
KW - Myrcludex-B
KW - NTCP
KW - T cell
UR - http://www.scopus.com/inward/record.url?scp=85071119765&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85071119765&partnerID=8YFLogxK
U2 - 10.1016/j.jhep.2019.07.003
DO - 10.1016/j.jhep.2019.07.003
M3 - Article
VL - 71
SP - 834
EP - 839
JO - Journal of Hepatology
JF - Journal of Hepatology
SN - 0168-8278
IS - 4
ER -