Early on-treatment HDV-RNA kinetics are not predictive for long-term response to a PEG-IFNa therapy of hepatitis delta

Wöbse, M.; Yurdaydın, Cihan; Ernst, Simone; Hardtke, Svenja; Heidrich, B.; Bremer, Birgit; Keskin, Özge; İdilman, Ramazan; Koch, Armin; Manns, MP; Wedemeyer, Heiner

doi:10.1055/s-0034-1397103

Cited by 6 publications

(9 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results from this study (Fig. B) suggest that LNF 100 mg BID with either RTV or PEG‐IFNα would result in a faster and greater HDV‐RNA reduction than a published study where patients received PEG‐IFNα 180 μg QW with or without tenofovir and only experienced a mean 2.78 log reduction after 48 weeks of therapy …”

Section: Discussionmentioning

confidence: 47%

“…(2) Treatment response is observed in around 25%-40% after 1 year of treatment (3)(4)(5)(6) and extending treatment to 2 years does not appear to increase response rates. (7)(8)(9) Still, there are data to suggest that IFN may need to be given for an extended duration of time, (10,11) which is consistent with in vitro studies that appear to lend support for longer treatment…”

mentioning

confidence: 59%

“…The only treatment with proven efficacy consists of the use of conventional or pegylated interferon (IFN) alpha (PEG‐IFNα) . Treatment response is observed in around 25%‐40% after 1 year of treatment and extending treatment to 2 years does not appear to increase response rates . Still, there are data to suggest that IFN may need to be given for an extended duration of time, which is consistent with in vitro studies that appear to lend support for longer treatment duration .…”

mentioning

confidence: 71%

See 2 more Smart Citations

Optimizing lonafarnib treatment for the management of chronic delta hepatitis: The LOWR HDV‐1 study

Yurdaydın¹,

Keskın²,

Kalkan³

et al. 2018

Hepatology

126

106

View full text Add to dashboard Cite

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. In addition, combining LNF with PEG-IFNα achieved more substantial and rapid HDV-RNA reduction, compared to historical responses with PEG-IFNα alone. Twelve weeks of LNF can result in posttreatment HDV-RNA negativity in some patients, which we speculate results from restoring favorable immune responses. These results support further development of LNF with RTV boosting and exploration of the combination of LNF with PEG-IFN. (Hepatology 2018;67:1224-1236).

show abstract

Section: Discussionmentioning

confidence: 47%

mentioning

confidence: 59%

mentioning

confidence: 71%

See 1 more Smart Citation

Optimizing lonafarnib treatment for the management of chronic delta hepatitis: The LOWR HDV‐1 study

Yurdaydın¹,

Keskın²,

Kalkan³

et al. 2018

Hepatology

126

106

View full text Add to dashboard Cite

show abstract

“…and 24 samples were available suggest that on-treatment week 24 performed better as treatment response predictor compared to earlier time points (15). Besides on-treatment serum HDV RNA, week 24 quantitative HBsAg levels displayed a difference by univariate but not by multivariate analysis.…”

Section: Discussionmentioning

confidence: 86%

Association Between Level of Hepatitis D Virus RNA at Week 24 of Pegylated Interferon Therapy and Outcome

Keskın

Wedemeyer

Tüzün

et al. 2015

Clinical Gastroenterology and Hepatology

View full text Add to dashboard Cite

“…During IFN therapy, the decline of HDV-RNA was biphasic with a first rapid phase, of about 1 month duration, followed by a second slower phase [21] . Early on treatment time points of HDV-RNA decline do not seem predictive of a sustained viral response (SVR) [22] ; a better predictor is a negative HDV-RNA test at 6 months of therapy.…”

Section: Current Therapymentioning

confidence: 99%

Chronic Hepatitis D; at a Standstill?

Rizzetto

2016

Dig Dis

View full text Add to dashboard Cite

Chronic hepatitis D (CHD) is a severe liver disease with worldwide distribution caused by the hepatitis D virus (HDV). Therapy of CHD is at a standstill. It still relies on interferon (IFN), introduced empirically in the 1980s; results are limited. With the peghilated IFNs that are now in use, only 25% of CHD reach a sustained viral response, that is, clear the HDV-RNA 6 months after stopping therapy. However, HDV remains infectious and ready to reactivate at very low titers undetectable by current assays, if the HBsAg persists in serum; relapses of hepatitis D post-therapy are frequent and further diminish the therapeutic response. The major obstacle to CHD therapy is the minimalist nature of the HDV. It does not encode for any enzymatic function but is replicated by host RNA polymerases deceived to recognize the viral RNA as it were a cellular DNA; therefore, it has no replicative machinery of its own to be targeted by antivirals. The only help required from hepatitis B virus (HBV) is the HBsAg coat to attach to hepatocytes and assembly in the virion; HBV antivirals that decrease HBV-DNA but leave HBsAg unaffected are of no avail in CHD. Novel therapeutic strategies are under evaluation. Myrcludex B, a peptidic inhibitor of HBV entry, was used with some success in vitro in the mouse to block the Na⁺-tauro chocolate cotransporting polypeptide and prevent entry of the HD virion into hepatocytes. The nuclei acid polymer REP-2139 was shown to distinctly diminish serum HBsAg and HDV-RNA by blocking HBsAg entry and inhibiting its intracellular synthesis. Prenylation of the large HD-antigen is critical for its interaction with the HBsAg in the assembly of the virion. A proof of concept study in humans has shown that the prenylation inhibitor lonafarnib reduced HDV-viremia.

show abstract

Early on-treatment HDV-RNA kinetics are not predictive for long-term response to a PEG-IFNa therapy of hepatitis delta

Cited by 6 publications

References 0 publications

Optimizing lonafarnib treatment for the management of chronic delta hepatitis: The LOWR HDV‐1 study

Optimizing lonafarnib treatment for the management of chronic delta hepatitis: The LOWR HDV‐1 study

Association Between Level of Hepatitis D Virus RNA at Week 24 of Pegylated Interferon Therapy and Outcome

Chronic Hepatitis D; at a Standstill?

Contact Info

Product

Resources

About