 |
|
|
| |
|
Pegasys vs Peg/ADV for Hepatitis D Virus: Pegasys most effective
|
| |
| |
A Multicenter Randomised Study Comparing the Efficacy of
Pegylated interferon-alfa-2a plus Adefovir dipivoxil
vs.
Pegylated interferon-alfa-2a plus Placebo
rr
vs.
Adefovir dipivoxil
for the Treatment of Chronic Delta Hepatitis
"The HIDIT-1 Study"
Reported by Jules Levin
EASL, April 2007, Barcelona, Spain
This investigator-initiated trial was supported by
- Roche Basel
- Gilead Sciences
- The Hep-Net Study House
C. Yurdaydin discloses that he has received research grants, lecturer fees, and travel support by Roche and Gilead
H. Wedemeyer discloses that he has received research grants, lecturer fees, and travel support by Roche and Gilead
AUTHOR SUMMARY
PEG-IFNa-2a reduces HDV-RNA levels by at least 2logs in approx. 40% of patients with 25% becoming HDV-RNA negative after 48 weeks.
24 weeks after the end of therapy, HDV-RNA was negative in 27% of patients (ITT-analysis).
Adefovir dipivoxil does not effect HDV-replication but reduces HBV-DNA levels.
Combination therapy of PEG-IFNa-2a plus adefovir was not superior in HDV-RNA suppression as compared to PEG-IFNa-2a alone.
Combination therapy was superior to either monotherapy in reducing HBsAg levels in HBV-HDV-coinfected patients.
AUTHOR CONCLUSIONS
PEG-IFNa-2a should be considered in the treatment of delta hepatitis.
Longer therapies in patients with good tolerability need to be evaluated.
Future trials need to confirm the increased HBsAg suppression of PEG-IFNa-2a plus nucleotide combination therapy.
BACKGROUND
Hepatitis D Virus (HDV)-Infection
--HDV is the smallest known virus to infect men
--HDV uses HBsAg as an envelope and thus can only be found as a coinfection with HBV
--HDV-infection affects approx. 15 Million people worldwide
--7-12% of HBsAg+ patients were anti-HDV+ at Hannover Medical between 1997 and 2006
Wedemeyer et al., Hepatology 2007 in press
--HDV genotype 1 is found in Europe and the Mediterranean Area and is associated with more severe disease
Su et al, Gastroenterology 2006
HDV-Infection Treatment Options
Interferon alpha
Sustained biochemical responses in 0-36% of patients
-Few Studies with virological endpoints
-treatment >12 months may be required
Farci et al., NEJM 1994
Di Marco et al., J Viral Hepatitis 1996
Niro et al., J Viral Hepatitis 2005
Higher IFN doses were associated with better survival in small study cohort
Farci et al., Gastroenterology 2004
Nucleos(t)ide Analogues
Famciclovir ineffective Yurdaydin et al., J Hepatol 2002
Lamivudine ineffective
Wolters et al., J Viral Hepatitis 2000
Niro, Aliment Pharmacol Ther. 2005
Niro et al., J Viral Hepatitis 2005
Ribavirin ineffective
Niro et al., Hepatology 2006
Garripoli et al., Liver 1994
Gunsar et al., Antiv Therapy 2005
Nucleos(t)ide Analogues
Famciclovir ineffective Yurdaydin
Trials using PEG-IFN in Delta Hepatitis
--3 studies published in September 2006
Castelnau, Gault et al. Hepatology 2006
14 patients, 12 months of PEG-IFN_-2b SVR in 6 patients (43%)
Niro, Rizzetto et al. Hepatology 2006
38 patients, 72 weeks PEG-IFN_-2b
16 pts monotherapy
22 pts + ribavirin (first 48 weeks)
SVR: 8 patients (21%)
Ribavirin had no additional effect
Erhardt, Haussinger et al. Liver Int 2006
12 patients, 48 weeks of PEG-IFN_-2b SVR in 2 patients (17%)
Inclusion Criteria
- Adults with chronic delta hepatitis
- Compensated liver disease
- HBsAg positive for at least 6 months
- anti HDV positive for at least 3 months
- HDV RNA positive by PCR
- ALT ≥ ULN to ≦10x ULN.
- Liver biopsy in the previous 12 months
- Negative tests for HCV-RNA & anti-HIV
- No treatment for hepatitis D in the prior 6 months
SAFETY
91 patients randomized (32 Peg/ADV, 29 Peg, 30 ADV)
--1 patient (Peg/ADV) withdrew IC before start of therapy
90 patients started therapy
--10 patients stopped treatment (5 Peg/ADV, 3 Peg alone, 2 ADV)
6 patients due to disease progression including 1 death (HCC) and 1 LTx
4 patients due to IFN-associated side effects
17 SAEs reported in 15 patients (17%)
--13 SAEs were considered as unrelated to study drug
--4 SAEs were considered as being related to Peg
311 AEs reported in 69 patients (76% of patients)
80 patients completed treatment.
|
| |
|
|
|
|
|
