Late HDV RNA relapse after peginterferon alpha‐based therapy of chronic hepatitis delta

@article{Heidrich2014LateHR,
  title={Late HDV RNA relapse after peginterferon alpha‐based therapy of chronic hepatitis delta},
  author={Benjamin Heidrich and Cihan Yurdaydın and G{\"o}khan Kabaçam and Boris A Ratsch and Kalliopi Zachou and Birgit Bremer and George N. Dalekos and Andreas Erhardt and Fehmi Tabak and Kendal Yalcin and Selim G{\"u}rel and Stefan Zeuzem and Markus Cornberg and C.-Thomas Bock and Michael P. Manns and Heiner Wedemeyer},
  journal={Hepatology},
  year={2014},
  volume={60}
}
Interferon alpha is the only treatment option for hepatitis delta virus (HDV). Trials investigating the efficacy of pegylated interferon alpha (PEG‐IFNa) showed HDV RNA negativity rates of 25‐30% 24 weeks after therapy. However, the clinical and virological long‐term outcome of HDV‐infected patients treated with PEG‐IFNa is unknown. We performed a retrospective‐prospective follow‐up of 77 patients treated for 48 weeks with either PEG‐alfa‐2a and adefovir (ADV) or either drug alone in the Hep… 
HBcrAg Levels Are Associated With Virological Response to Treatment With Interferon in Patients With Hepatitis Delta
TLDR
HBcrAg is linked to treatment response to peg‐IFNα in patients with HBV/HDV co‐infection and could be a promising marker to determine treatment futility.
Ten‐year follow‐up of a randomized controlled clinical trial in chronic hepatitis delta
TLDR
Long‐term follow‐up of a large randomized clinical trial suggests that off‐treatment HDV RNA response to PEG‐IFNα‐2a treatment leads to improved clinical long‐term outcome.
Antiviral treatment and liver‐related complications in hepatitis delta
TLDR
Loss of HDV RNA during follow‐up was more frequent in IFNα‐treated patients and strongly linked with a lower likelihood to experience liver‐related complications, and Durable undetectability ofHDV RNA is a valid surrogate endpoint in the treatment of hepatitis delta.
Co-treatment with pegylated interferon alfa-2a and entecavir for hepatitis D: A randomized trial.
TLDR
Administration of PEG-IFNα-2a with or without entecavir, resulted in persistent HDV RNA clearance in 37% of patients, and the addition of entecvir did not improve the overall response.
Antiviral treatment with pegylated interferon and clinical outcomes in a cohort of immigrants patients affected by hepatitis delta: A retrospective analysis
TLDR
Treatment of CHD is limited by poor virological response; is NR unfavorable outcomes were unavoidable; no other treatment options were available.
Optimizing lonafarnib treatment for the management of chronic delta hepatitis: The LOWR HDV‐1 study
TLDR
The cytochrome P450 3A4 inhibitor, RTV, allows a lower LNF dose to be used while achieving higher levels of postabsorption LNF, yielding better antiviral responses and tolerability and support further development of LNF with RTV boosting and exploration of the combination of L NF with PEG‐IFN.
A transient early HBV‐DNA increase during PEG‐IFNα therapy of hepatitis D indicates loss of infected cells and is associated with HDV‐RNA and HBsAg reduction
TLDR
An early increase in HBV‐DNA during PEG‐IFNα‐2a therapy occurred in more than 20% of patients, even in TDF‐treated patients, which may indicate PEG­IFN α–induced cell death and lead to long‐term HDV‐RNA suppression and HBsAg loss.
Letter: the potential success of long‐term therapy of chronic delta hepatitis with peginterferon alfa – authors' reply
  • C. Koh, T. Heller
  • Medicine, Biology
    Alimentary pharmacology & therapeutics
  • 2015
TLDR
The experience strengthens the idea of very prolonged treatment with peginterferon alfa in selected patients, that is, those able to tolerate the therapy, even those with advanced compensated liver disease, and when close monitoring of biochemical and virological parameters is feasible.
Interferon Treatment Duration in Patients With Chronic Delta Hepatitis and its Effect on the Natural Course of the Disease
TLDR
Viral response to interferon increases with treatment duration and favorably affects the natural course of disease.
...
...

References

SHOWING 1-10 OF 50 REFERENCES
Efficacy of peginterferon alpha‐2b in chronic hepatitis delta: Relevance of quantitative RT‐PCR for follow‐up
TLDR
A preliminary study indicates that PEG‐IFN alpha‐2b is safe and efficient for treatment of chronic hepatitis delta, and the follow‐up of HDV‐RNA levels during therapy, which allows the differentiation of various profiles of virological responses, improves treatment monitoring.
Patterns of viral decline during PEG‐interferon alpha‐2b therapy in HBeAg‐positive chronic hepatitis B: Relation to treatment response
TLDR
Different patterns of decline in viral load during treatment with PEG‐IFN monotherapy were associated with different rates of HBeAg and HBsAg loss at the end of follow-up.
Pegylated interferon alpha‐2b as monotherapy or in combination with ribavirin in chronic hepatitis delta
TLDR
A prolonged course of peginterferon alpha‐2b resulted in clearance of serum HDV RNA and ALT normalization in a fifth of patients with chronic hepatitis D, while ribavirin had no effect on the viral clearance rate.
Treatment of chronic hepatitis delta with pegylated interferon-alpha2b.
TLDR
It is indicated that PEG-IFN-alpha2b is a promising treatment option in chronic hepatitis D and nonresponders could be identified by a less than 3 log decrease of HDV RNA at 6 months of treatment.
Interferon α‐2b with and without ribavirin in the treatment of hepatitis B e antigen–positive chronic hepatitis B: A randomized study
TLDR
For the treatment of HBeAg‐positive chronic hepatitis B, adding ribavirin does not seem to increase the efficacy of IFN, except that the IFN/ribavirin group had a higher risk of anemia.
Resolution of chronic hepatitis Delta after 1 year of combined therapy with pegylated interferon, tenofovir and emtricitabine.
  • Wael Mansour, A. Ducancelle, F. Lunel
  • Medicine, Biology
    Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology
  • 2010
Peginterferon alpha‐2b plus adefovir induce strong cccDNA decline and HBsAg reduction in patients with chronic hepatitis B
TLDR
Combined therapy with peg‐IFN and ADV led to marked decreases in serum HBV‐DNA and intrahepatic cccDNA, which was significantly correlated with reduced HBsAg, suggesting the involvement of cytolytic mechanisms.
Long‐term clinical and virological outcome after liver transplantation for cirrhosis caused by chronic delta hepatitis
TLDR
In conclusion, liver transplantation for HDV cirrhosis gives good results, with a 5‐year actuarial survival of 88%, and HDV markers were detectable during the first year, without the development of hepatitis, but disappeared in the long term in most cases.
Clinical outcome of acute and chronic hepatitis delta over time: a long‐term follow‐up study
TLDR
These results indicate an outbreak of HDV at the end of the 1980s and the beginning of the 1990s, with a large number of acute HDV cases affecting predominately young, male intravenous drug users.
Hepatitis D virus‐specific cytokine responses in patients with chronic hepatitis delta before and during interferon alfa‐treatment
TLDR
The role of the adaptive immune system in controlling HDV infection during spontaneous or treatment‐induced viral clearance is not well understood and the need for further research into this area is unclear.
...
...