scholarly journals Hepatitis C virus-associated cryoglobulinemic vasculitis: A 20-year experience with treatment

2017 ◽  
Vol 89 (5) ◽  
pp. 46-52 ◽  
Author(s):  
T M Ignatova ◽  
L V Kozlovskaya ◽  
N B Gordovskaya ◽  
O A Chernova ◽  
S Yu Milovanova ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Combined Therapy ◽  
Multivariate Logistic Regression Analysis ◽  
Virologic Response ◽  
Term Treatment ◽  
Cryoglobulinemic Vasculitis ◽  
Multidisciplinary Therapy ◽  
Long Term Treatment

Aim. To summarize the experience of a multidisciplinary therapy hospital in treating patients with hepatitis C virus (HCV)-associated cryoglobulinemic vasculitis (CV). Subjects and methods. Seventy-two patients (mean age, 49.4±10.3 years) with HCV-associated CV were examined and followed up for an average period of 2.8±3.6 years. The efficiency of traditional (corticosteroids ± cyclophosphamide) and selective (rituximab) immunosuppressive therapy (IST) was estimated in 31 and 15 observations, respectively, and that of antiviral therapy (AVT) in 25. Vasculitis activity was assessed using the Birmingham vasculitis activity score (BVAS). The patients’ survival was studied; multivariate logistic regression analysis was carried out. Results. 24 (33.4%) of the 72 patients had a stage of liver cirrhosis (LC). The pretreatment mean BVAS was 11.9±7.2 (range 2 to 36). Severe CV (BVAS ≥15) was present in 30.6% of the patients. AVT was accompanied by achievement of sustained virologic response in 48% of the patients, clinical remission in 68% and had an advantage over IST in relation to long-term treatment results. Rituximab was significantly more effective than traditional immunosuppressants (remission rates of 73 and 13%, respectively). Combined therapy (rituximab and AVT) was most effective in patients with severe forms of vasculitis. Sixteen patients died from complications of vasculitis (37.5%), infection (37.5%), and LC (25%). The factors adversely affecting prognosis were age >55 years (odds ratio (OR), 4.49), the presence of LC (OR, 3.68), renal failure (OR, 4.66) and the use of glucocorticosteroids (OR, 3.91). Conclusion. HCV-associated CV can determine the prognosis of chronic HСV infection. AVT is the treatment of choice in all patients with HСV-associated CV. AVT must be combined with rituximab therapy in patients with severe forms of vasculitis.

scholarly journals NIM811, a Cyclophilin Inhibitor, Exhibits Potent In Vitro Activity against Hepatitis C Virus Alone or in Combination with Alpha Interferon

2006 ◽  
Vol 50 (9) ◽  
pp. 2976-2982 ◽  
Author(s):  
Sue Ma ◽  
Joanna E. Boerner ◽  
ChoiLai TiongYip ◽  
Beat Weidmann ◽  
Neil S. Ryder ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Clinical Investigation ◽  
Term Treatment ◽  
Alpha Interferon ◽  
Hcv Rna ◽  
Long Term Treatment ◽  
Antiviral Targets

ABSTRACT Host factors involved in viral replication are potentially attractive antiviral targets that are complementary to specific inhibitors of viral enzymes, since resistant mutations against the latter are likely to emerge during long-term treatment. It has been reported recently that cyclosporine, which binds to a family of cellular proteins, cyclophilins, inhibits hepatitis C virus (HCV) replication in vitro. Here, the activities of various cyclosporine derivatives were evaluated in the HCV replicon system. There was a strong correlation between the anti-HCV activity and cyclophilin-binding affinity of these compounds. Of these, NIM811 has been selected as a therapeutic candidate for HCV infection, since it binds to cyclophilins with higher affinity than cyclosporine but is devoid of the significant immunosuppressive activity associated with cyclosporine. NIM811 induced a concentration-dependent reduction of HCV RNA in the replicon cells with a 50% inhibitory concentration of 0.66 μM at 48 h. Furthermore, a greater than three-log10 viral RNA reduction was achieved after treating the cells with as little as 1 μM of NIM811 for 9 days. In addition, the combination of NIM811 with alpha interferon significantly enhanced anti-HCV activities without causing any increase of cytotoxicity. Taken together, these promising in vitro data warrant clinical investigation of NIM811, an inhibitor of novel mechanism, for the treatment of hepatitis C.

scholarly journals Long-Term Treatment With Natural Alpha-IFN in Hepatitis C Recurrence After OLT

2011 ◽  
Vol 140 (5) ◽  
pp. S-901
Author(s):  
Federica Buonfiglioli ◽  
Maria Rosa Tamè ◽  
Francesca Lodato ◽  
Antonio Colecchia ◽  
Francesco Azzaroli ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Term Treatment ◽  
Long Term Treatment ◽  
Hepatitis C Recurrence

PD23-06 CHANGE IN SEXUAL FUNCTION IN MEN WITH LUTS/BPH ASSOCIATED WITH LONG-TERM TREATMENT WITH DOXAZOSIN, FINASTERIDE, AND COMBINED THERAPY

2014 ◽  
Vol 191 (4S) ◽  
Author(s):  
R. Charles Welliver ◽  
Chyng-Wen Fwu ◽  
Paul W. Eggers ◽  
Ziya Kirkali ◽  
Kevin T. McVary ◽  
...  
Keyword(s):  
Sexual Function ◽  
Combined Therapy ◽  
Term Treatment ◽  
Long Term Treatment

scholarly journals Herbal product use by persons enrolled in the hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial

Hepatology ◽  
2007 ◽  
Vol 47 (2) ◽  
pp. 605-612 ◽  
Author(s):  
Leonard B. Seeff ◽  
Teresa M. Curto ◽  
Gyongyi Szabo ◽  
Gregory T. Everson ◽  
Herbert L. Bonkovsky ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Herbal Product ◽  
Term Treatment ◽  
Product Use ◽  
Long Term Treatment

scholarly journals HCV RNA detection by TMA during the hepatitis C antiviral long-term treatment against cirrhosis (Halt-C) trial

Hepatology ◽  
2006 ◽  
Vol 44 (2) ◽  
pp. 360-367 ◽  
Author(s):  
Chihiro Morishima ◽  
Timothy R. Morgan ◽  
James E. Everhart ◽  
Elizabeth C. Wright ◽  
Mitchell L. Shiffman ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Term Treatment ◽  
Hcv Rna ◽  
Rna Detection ◽  
Long Term Treatment

scholarly journals Preclinical Evaluation of Amphihevir, a First-in-Class Clinical Hepatitis C Virus NS4B Inhibitor

2019 ◽  
Vol 63 (12) ◽  
Author(s):  
Xin Tao ◽  
Ningyu Wang ◽  
Jianfei Wang ◽  
Zhifei Fu ◽  
Zhengxian Gu ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Nonstructural Protein ◽  
Preclinical Study ◽  
Term Treatment ◽  
Cross Resistance ◽  
Pharmacokinetic Studies ◽  
Genotype 1B ◽  
Long Term Treatment ◽  
Antiviral Activities

ABSTRACT Amphihevir, a benzofuran derivative, is the first reported hepatitis C virus (HCV) nonstructural protein 4B (NS4B) inhibitor that has advanced to clinical trials (currently in phase Ib trial [CTR20170632]). Here, we report the results of a preclinical study of its potency, toxicity, selectivity, drug metabolism and pharmacokinetics (DMPK), and safety profiles. Amphihevir displayed good antiviral activities against genotype 1a (50% effective concentration [EC50] of 0.34 nM) and genotype 1b (EC50 of 1.97 nM) replicons and no cytotoxicity in 12 cell lines derived from animals and humans. Amphihevir was found to be inactive against other viruses, human kinases, and G protein-coupled receptors (GPCRs), which implies its good selectivity. A 9-day long-term treatment of genotype 1b replicons with amphihevir resulted in a 3.8 Log10 decline of the hepatitis C viral RNA at a concentration of 25× EC90. Drug resistance screening showed that mutations occurred at H94, F98, and V105 of NS4B, which mediated the resistance to amphihevir. This result suggests that NS4B is the main target of amphihevir. There was no cross-resistance between amphihevir and NS5A, NS3/4A, and NS5B inhibitors, suggesting that amphihevir in combination with other anti-hepatitis C virus drugs could be used to treat hepatitis C, as proven by studies of amphihevir and other hepatitis C virus inhibitors. Pharmacokinetic studies demonstrated that amphihevir has good oral bioavailability and appropriate half-life (t1/2) in rats and dogs, thereby supporting its use once per day. Finally, amphihevir showed good safety profiles in rats and dogs. The results shed light on the use of amphihevir as a potential treatment option for chronic hepatitis C patients.

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