scholarly journals Pegylated-interferon plus ribavirin treatment does not alter the prevalence of resistance-associated substitutions to direct-acting antivirals in HCV genotype 1a patients

2017 ◽  
Vol Volume 10 ◽  
pp. 275-281 ◽  
Author(s):  
Zhi-wei Chen ◽  
Xi-chen Pang ◽  
Zhao Li ◽  
Hong Ren ◽  
Peng Hu
Keyword(s):  
Pegylated Interferon ◽  
Direct Acting Antivirals ◽  
Hcv Genotype ◽  
Genotype 1A ◽  
Pegylated Interferon Plus Ribavirin ◽  
Direct Acting

A hepatitis C-vírus-bázispolimorfizmus jelentősége a kezelésben

2015 ◽  
Vol 156 (21) ◽  
pp. 849-854 ◽  
Author(s):  
István Tornai
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Protease Inhibitors ◽  
First Generation ◽  
Pegylated Interferon ◽  
Direct Acting Antivirals ◽  
Direct Acting Antiviral ◽  
Genotype 1A ◽  
Direct Acting ◽  
Ns5b Polymerase

The treatment of chronic hepatitis C has developed significantly during the last 25 years. In patients with genotype 1 infection 40–50% sustained virologic response could be achieved using pegylated interferon and ribavirin dual combination, which could be increased significantly with the introduction of direct acting antivirals. Three major groups of direct acting antivirals are known, which directly inhibit different phases of viral life cycle, by inhibiting the function of several non-structural proteins (NS3/4A protease, NS5A protein and NS5B polymerase). Due to the rapid replication rate of hepatitis C virus and the error-prone NS5B polymerase activity, mutant virions are generated, which might have reduced susceptibility to direct acting antiviral therapy. Since these resistance associated variants might exist before the antiviral therapy, they are still able to replicate during the direct acting antiviral treatment. Due to this selection pressure, the resistant virus will replace the wild type. This was especially detected during monotherapy, therefore, the first generation of direct acting antivirals have been combined with pegylated interferon and ribavirin, while recently interferon-free combinations are being developed including 2 or 3 direct acting antivirals. Using the first generation protease inhibitors boceprevir and telaprevir, it could have been seen, that the rate of resistance associated variants is higher and the therapeutic outcome is worse in patients with hepatitis C virus genotype 1a, than in 1b. Similar phenomenon was seen with the second generation of NS3/4A protease inhibitors as well as with NS5A or NS5B polymerase. This is due to the lower genetic barrier to resistance, ie. usually fewer mutations are enough for the emergence of resistance in genotype 1a. The selection of resistance associated variants is one of the most important challenges during the interferon-free therapy. Orv. Hetil., 2015, 156(21), 849–854.

scholarly journals Effectiveness, tolerability and safety of Direct Acting Antivirals in Mexican individuals with Hepatitis C virus genotype-1 and previous pegylated interferon and ribavirin therapy

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12051
Author(s):  
Daniel Melendez-Mena ◽  
Miguel Angel Mendoza-Torres ◽  
Virginia Sedeño-Monge ◽  
Víctor Hugo García y García ◽  
Elain Rivera-García ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Pegylated Interferon ◽  
Direct Acting Antivirals ◽  
Virus Genotype ◽  
Liver Transaminase ◽  
Genotype 1A ◽  
Before And After ◽  
Liver Transaminases ◽  
Cirrhotic Patients ◽  
Direct Acting

Background Direct Acting Antivirals (DAAs) represent a large improvement in the treatment of chronic hepatitis C, resulting in <90% sustained virological response (SVR). There are no reports on the real-world DAA response for Mexico and few reports exist for Latin America. The aim of the study was to report SVR, and immediate benefits with the DAA treatments sofosbuvir, ledispavir, with/without ribavirin (SOF/LDV ± RBV) and ombitasvir, paritaprevir, ritonavir, dasabuvir with/without RBV (OBV/PTV/r/DSV ± RBV) in patients with viral genotype 1a or 1b, and who did not respond to previous peginterferon/ribavirin (PegIFNα2a+RBV) therapy. Methods A descriptive, ambispective, longitudinal study was conducted. A cohort of 261 adult patients received PegIFNα2a+RBV therapy before 2014; 167 (64%) did not respond, 83 of these were subsequently treated with SOF/LDV ± RBV or OBV/PTV/r/DSV ± RBV. Child-Pugh-Score (CPS), Fibrosis-4 (FIB-4), and AST to Platelet Ratio Index (APRI) were evaluated before and after treatment. Results SVR with PegIFNα2a+RBV was 36%, and 97.5% with DAAs. CPS, FIB-4 and APRI improved significantly after DAA treatment, mainly because of liver transaminase reduction. Conclusions DAA treatment showed excellent SVR rates in Mexican patients who had not responded to PegIFNα2a+RBV therapy. Improvement in CPS, FIB-4 and APRI without improvement in fibrosis was observed in cirrhotic and non-cirrhotic patients, as well as considerable reduction in liver transaminases, which suggests a reduction in hepatic necroinflammation.

scholarly journals A hepatitis C-vírus-fertőzés szűrése, diagnosztikája, antivirális terápiája, kezelés utáni gondozása. Magyar konszenzusajánlás. Érvényes: 2016. október 15-től

2017 ◽  
Vol 158 (Supplement 1) ◽  
pp. 3-22 ◽  
Author(s):  
Béla Hunyady ◽  
Zsuzsanna Gerlei ◽  
Judit Gervain ◽  
Gábor Horváth ◽  
Gabriella Lengyel ◽  
...  
Keyword(s):  
Liver Disease ◽  
Hepatitis C ◽  
Disease Risk ◽  
Dual Therapy ◽  
Pegylated Interferon ◽  
Insurance Fund ◽  
Hepatic Decompensation ◽  
Direct Acting Antiviral ◽  
Pegylated Interferon Plus Ribavirin ◽  
Direct Acting

Treatment of hepatitis C is based on a national consensus guideline updated six-monthly according to local availability and affordability of approved therapies through a transparent allocation system in Hungary. This updated guideline incorporates some special new aspects, including recommendations for screening, diagnostics, use and allocation of novel direct acting antiviral agents. Indication of therapy in patients with no contraindication is based on demonstration of viral replication with consequent inflammation and/or fibrosis in the liver. Non-invasive methods (elastographies and biochemical methods) are preferred for liver fibrosis staging. The budget allocated for these patients is limited. Therefore, expensive novel direct acting antiviral combinations as first line treatment are reimbursed only, if the freely available, but less effective and more toxic pegylated interferon plus ribavirin dual therapy deemed to prone high chance of adverse events and/or low chance of cure. Priority is given to those with urgent need based on a pre-defined scoring system reflecting mainly the stage of the liver disease, but considering also additional factors, i.e., hepatic decompensation, other complications, activity and progression of liver disease, risk of transmission and other special issues. Approved treatments are restricted to the most cost-effective combinations based on the cost per sustained virological response value in different patient categories with consensus amongst treating physicians, the National Health Insurance Fund and patient’s organizations. Interferon-free treatments and shorter therapy durations are preferred. Orv. Hetil., 2017, 158(Suppl. 1), 3–22.

scholarly journals Hepatocellular Carcinoma Risk According to Regimens for Eradication of Hepatitis C Virus; Interferon or Direct Acting Antivirals

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3414
Author(s):  
Hye Won Lee ◽  
Dai Hoon Han ◽  
Hye Jung Shin ◽  
Jae Seung Lee ◽  
Seung Up Kim ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Pegylated Interferon ◽  
Direct Acting Antivirals ◽  
Treatment Regimens ◽  
Direct Acting ◽  
Similar Risk ◽  
Carcinoma Risk

By pegylated interferon (PegIFN)-free direct-acting antivirals (DAAs) against hepatitis C virus (HCV) infection, a sustained virological response (SVR) rate >95% can be attained with a satisfactory tolerability and shorter treatment duration. However, it remains controversial whether there is any difference in prognosis depending on regimens—PegIFN or DAAs. We compared the probabilities of hepatocellular carcinoma (HCC) development between patients achieving an SVR by PegIFN/ribavirin (PegIFN group, n = 603) and DAAs (DAAs group, n = 479). The DAAs group was significantly older and had a higher proportion of cirrhosis than the PegIFN group. Before adjustment, the DAAs group had a higher HCC incidence than the PegIFN group (p < 0.001). However, by multivariate analyses, the DAAs (vs. PegIFN) group was not associated with HCC risk (adjusted hazard ratio 0.968, 95% confidence interval 0.380–2.468; p = 0.946). Old age, male, higher body mass index, cirrhosis, and lower platelet count were associated with increased HCC risk (all p < 0.05). After propensity score matching (PSM), a similar HCC risk between the two groups was observed (p = 0.372). We also compared HCC incidences according to sofosbuvir (SOF)-based and SOF-free DAAs, showing a similar risk in both groups before adjustment (p = 0.478) and after PSM (p = 0.855). In conclusion, post-SVR HCC risks were comparable according to treatment regimens; PegIFN- vs. DAA-based regimens and SOF-based vs. SOF-free DAA regimens. Further studies with a longer follow-up period are required.

scholarly journals Hepatitis C Virus NS3 Inhibitors: Current and Future Perspectives

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Kazi Abdus Salam ◽  
Nobuyoshi Akimitsu
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Protease Inhibitors ◽  
Standard Of Care ◽  
Pegylated Interferon ◽  
Virologic Response ◽  
Hcv Infection ◽  
Main Concern ◽  
Pegylated Interferon Plus Ribavirin ◽  
Direct Acting

Currently, hepatitis C virus (HCV) infection is considered a serious health-care problem all over the world. A good number of direct-acting antivirals (DAAs) against HCV infection are in clinical progress including NS3-4A protease inhibitors, RNA-dependent RNA polymerase inhibitors, and NS5A inhibitors as well as host targeted inhibitors. Two NS3-4A protease inhibitors (telaprevir and boceprevir) have been recently approved for the treatment of hepatitis C in combination with standard of care (pegylated interferon plus ribavirin). The new therapy has significantly improved sustained virologic response (SVR); however, the adverse effects associated with this therapy are still the main concern. In addition to the emergence of viral resistance, other targets must be continually developed. One such underdeveloped target is the helicase portion of the HCV NS3 protein. This review article summarizes our current understanding of HCV treatment, particularly with those of NS3 inhibitors.

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