scholarly journals Recent advances in managing chronic HCV infection: focus on therapy in patients with severe liver disease

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 367 ◽  
Author(s):  
Raoel Maan ◽  
Adriaan J. van der Meer
Keyword(s):  
Liver Disease ◽  
Treatment Options ◽  
Public Health Problem ◽  
Hcv Infection ◽  
New Drugs ◽  
European Medicines Agency ◽  
Major Public Health Problem ◽  
Advanced Liver Disease ◽  
Specific Patient ◽  
Chronic Hcv

Chronic hepatitis C virus (HCV) infection still represents a major public health problem, as it is thought to be responsible for more than 350,000 deaths around the globe on a yearly basis. Fortunately, successful eradication of the virus has been associated with improved clinical outcome and reduced mortality rates. In the past few years, treatment has improved considerably by the implementation of direct-acting antivirals (DAAs). From 2014 onwards, sofosbuvir, simeprevir, daclatasvir, ledipasvir, paritaprevir, ombitasvir, and dasabuvir have been approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA). Regimens with various combinations of these new drugs, without the use of interferon (IFN), proved to be very effective and well tolerated, even among patients with advanced liver disease. Moreover, treatment duration could be shortened to 12 weeks in the majority of patients. The high costs of these DAAs, however, limit the availability of IFN-free therapy worldwide. Even in wealthy countries, it is deemed necessary to prioritize DAA treatment in order to limit the immediate impact on the health budget. As patients with advanced liver disease are in most need of HCV clearance, many countries decided to treat those patients first. In the current review, we focus on the currently available IFN-free treatment options for patients with cirrhosis. We discuss the virological efficacy as well as the clinical relevance of these regimens among this specific patient population.

Explorative analysis of expanded access for intermediate-size and larger patient populations.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19070-e19070 ◽  
Author(s):  
Andriy Krendyukov
Keyword(s):  
Access To Care ◽  
Public Health Problem ◽  
New Drugs ◽  
European Medicines Agency ◽  
Major Public Health Problem ◽  
Expanded Access ◽  
Early Access ◽  
The Usa ◽  
Intermediate Size ◽  
Patient Groups

e19070 Background: Cancer is a major public health problem worldwide and is the second leading cause of death in the USA. While continuous efforts are being made by the US Food and Drug Administration to bring more new oncology products (NOP) to patients, there is a high unmet medical need for oncology patients to get access to care, and in particular access to NOP outside of clinical trials before the NOP is approved or commercialized. To improve access to NOP, several pathways are endorsed by competent authorities including: early dialogue with regulatory agencies; accelerated assessments; conditional marketing authorization; and early access provision, known as expanded access (EA) in the USA and compassionate use (CU) in the EU. Methods: A literature search and explorative analysis of available EA data from Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) relating to submission and approval of existing or investigational new drugs (IND) was performed for individual (single) patient emergency and non-emergency IND (IPIND), intermediate size IND (ISIND), and treatment IND (TIND). The findings were compared to centralized CU programs. The analysis was primarily focused on understanding the current landscape of EA for patient groups compared with individual patient categories. Results: Based on available CDER and CBER data submissions for ISIND and TIND categories were dramatically low compared with IPIND and total applications for EA: 1.25% (ISIND) and 0.13% (TIND) out of 1,598 EA applications received in 2018; and respectively 2.7% and 0.11% out of 1,741 EA applications in 2017; 2.6% and 0.24% out of 1,634 EA applications in 2016; 3.6% and 0.15% out of 1,328 EA applications in 2015; and 2.8% and 0.05% out of 1,886 EA applications in 2014. A high approval rate was reported for all three EA categories, and in particular approval of 95% (174 out 183) for ISIND and 100% (1 application) for TIND by CDER, and approval of 89% (24 out of 27) for ISIND and 80% (8 out of 10) for TIND by CBER. No applications for CU were reported by the European Medicines Agency for the same period of time, however several oncological products have been approved for CU in some European countries. Conclusions: Despite high approval rates, applications for ISIND and TIND remain low, especially in comparison to IPIND. In the absence of, or limited, alternative treatments, access provision to patient groups such as ISIND and TIND in the USA, and CU in the European Union, might represent an underutilized opportunity for oncological patients to obtain early access to care.

scholarly journals In search of an ideal drug for safer treatment of obesity: The false promise of pseudoephedrine

2021 ◽  
Author(s):  
Antonio Munafò ◽  
Stefano Frara ◽  
Norberto Perico ◽  
Rosaria Di Mauro ◽  
Monica Cortinovis ◽  
...  
Keyword(s):  
Adverse Events ◽  
Treatment Options ◽  
Public Health Problem ◽  
Cardiovascular Death ◽  
Regulation Of Transcription ◽  
Major Public Health Problem ◽  
Obese Patients ◽  
Ephedra Sinica ◽  
The Central Nervous System ◽  
Treatment Of Obesity

AbstractObesity is a major public health problem worldwide. Only relatively few treatment options are, at present, available for the management of obese patients. Furthermore, treatment of obesity is affected by the widespread misuse of drugs and food supplements. Ephedra sinica is an old medicinal herb, commonly used in the treatment of respiratory tract diseases. Ephedra species contain several alkaloids, including pseudoephedrine, notably endowed with indirect sympathomimetic pharmacodynamic properties. The anorexigenic effect of pseudoephedrine is attributable primarily to the inhibition of neurons located in the hypothalamic paraventricular nucleus (PVN), mediating satiety stimuli. Pseudoephedrine influences lipolysis and thermogenesis through interaction with β3 adrenergic receptors and reduces fat accumulation through down-regulation of transcription factors related to lipogenesis. However, its use is associated with adverse events that involve to a large extent the cardiovascular and the central nervous system. Adverse events of pseudoephedrine also affect the eye, the intestine, and the skin, and, of relevance, sudden cardiovascular death related to dietary supplements containing Ephedra alkaloids has also been reported. In light of the limited availability of clinical data on pseudoephedrine in obesity, along with its significantly unbalanced risk/benefit profile, as well as of the psychophysical susceptibility of obese patients, it appears reasonable to preclude the prescription of pseudoephedrine in obese patients of any order and degree.

Fatigue, depression and chronic hepatitis C infection

2002 ◽  
Vol 32 (1) ◽  
pp. 1-10 ◽  
Author(s):  
SIMON WESSELY ◽  
CARMINE PARIANTE
Keyword(s):  
Liver Disease ◽  
Hepatitis C ◽  
Hcv Infection ◽  
Review Of The Literature ◽  
Hepatitis C Infection ◽  
Epidemiological Evidence ◽  
Advanced Liver Disease ◽  
Specialist Referral ◽  
Lack Of Exercise ◽  
The Moment

Background. We aimed to determine if an association exists between uncomplicated hepatitis C virus (HCV) infection and depression or fatigue.Method. A review of the literature was undertaken.Results. There is an association between HCV infection and either depression or fatigue in certain circumstances – those who are aware they are HCV positive, those with advanced liver disease and those seen in specialist referral centres. All these studies are subject to important biases. There are only a few studies in which knowledge of HCV status and assessment of fatigue or depression is independent. These studies do not suggest an association. There is no association between conventional markers of liver disease and depression or fatigue.Conclusions. Despite anecdotal evidence to the contrary, at the moment there is no evidence that HCV infection per se is associated with fatigue or depression, and there is a suggestion that it is not. The same risk factors that exist for fatigue in other physical illnesses, such as metabolic disorder, mood disorder, demographics and lack of exercise, certainly exist for HCV. Although there are elegant theoretical mechanisms, there is no compelling epidemiological evidence for an additional HCV specific fatigue or depression factor.

Antibody Development to HCV Alternate Reading Frame Protein in Liver Transplant Candidate and its Computational Analysis

2020 ◽  
Vol 17 (2) ◽  
pp. 154-170 ◽  
Author(s):  
Zahra Musavi ◽  
Tayebeh Hashempour ◽  
Javad Moayedi ◽  
Behzad Dehghani ◽  
Farzaneh Ghassabi ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Transplant ◽  
Chronic Patients ◽  
Advanced Liver Disease ◽  
Reading Frame ◽  
Alternate Reading Frame Protein ◽  
Physicochemical Features ◽  
Liver Transplant Candidate ◽  
Transplant Candidate ◽  
Chronic Hcv

Background:: HCV Alternate Reading Frame Protein (ARFP) is a frameshift product of HCV-core encoding. Here, we characterized specific anti-ARFP antibodies in Liver Transplant Candidate (LTC) and chronic HCV-infected patients. Methods:: The ARFP gene was cloned and the recombinant protein was purified using Nickel chromatography and confirmed by western blotting. ELISA was developed using recombinant core-1a, core- 1b, ARFP-1a protein, and 99-residue synthetic ARFP 1b peptide. By several Bioinformatics tools, general properties, immunogenic epitopes, and structures of these proteins were obtained. Results:: The seroprevalence of anti-core and anti-ARFP antibodies was 100% in LTC patients, but only 75.2% and 94.3% of chronic patients had evidence of anti-ARFP and anti-core antibodies, respectively. In-silico results demonstrated physicochemical features, antigen properties and potential interactors that could describe progression toward advanced liver disease. Conclusion:: As the first report, the prevalence of anti-ARFP antibodies in LTC patients is of the order of 100% and titer of anti-ARFP antibody was significantly higher in LTC patients compared to chronic individuals, suggesting the possible role of ARFP in the progression toward advanced liver disease. In addition, docking analysis determined several interactor proteins such as prefoldin 2, cathepsin B, vitronectin, and angiotensinogen that have an important role in progression to chronic infection and liver disease development.

scholarly journals High Prognostic Value of Mini-Laparoscopy for Advanced Liver Disease-Related Complications in Patients with HCV Infection

Digestion ◽  
2016 ◽  
Vol 94 (2) ◽  
pp. 114-122
Author(s):  
Eugen Zizer ◽  
Johanna Backhus ◽  
Stephan Bohl ◽  
Anette Braun ◽  
Irina Baturina ◽  
...  
Keyword(s):  
Liver Disease ◽  
Prognostic Value ◽  
Hcv Infection ◽  
Advanced Liver Disease

scholarly journals Ledipasvir and Sofosbuvir Plus Ribavirin for Treatment of HCV Infection in Patients With Advanced Liver Disease

2015 ◽  
Vol 149 (3) ◽  
pp. 649-659 ◽  
Author(s):  
Michael Charlton ◽  
Gregory T. Everson ◽  
Steven L. Flamm ◽  
Princy Kumar ◽  
Charles Landis ◽  
...  
Keyword(s):  
Liver Disease ◽  
Hcv Infection ◽  
Advanced Liver Disease
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