Host-Targeting Antivirals for Treatment of Hepatitis C

2021 ◽  
Author(s):  
Bouchra Kitab ◽  
Michinori Kohara ◽  
Kyoko Tsukiyama-Kohara
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Host Cell ◽  
Chronic Hepatitis C ◽  
Standard Of Care ◽  
Hcv Infection ◽  
Current Standard ◽  
Host Cell Factors ◽  
Direct Acting ◽  
Cure Rates

Treatment of chronic hepatitis C virus (HCV) infection has been revolutionized during last years with the development of highly potent direct-acting antivirals (DAAs) specifically targeting HCV proteins. DAAs are the current standard of care for patients with chronic hepatitis C, leading to high cure rates. However, some hurdles exist including the high cost of these therapies restricting access to patients, their inability to protect against the risk of developing hepatocellular carcinoma in patients with advanced fibrosis, and emergence of resistant variants resulting in treatment failure. New therapeutic options should be essential to overcome DAAs limitations and improve survival. By targeting host-cell factors involved in HCV life cycle, host-targeting antivirals (HTAs) offer opportunity for promising anti-HCV therapy with low mutational rate and may act in a synergistic manner with DAAs to prevent viral resistance and reduce viral replication. Moreover, HTAs could be effective in difficult-to-cure patients by acting through complementary mechanisms. In this chapter, we will focus on the latest and most relevant studies regarding the host-cell factors required in HCV infection and explored as targets of antiviral therapy, we will also discuss the HTAs evaluated in preclinical and clinical development and their potential role as alternative or complementary therapeutic strategies.

scholarly journals Novel emerging treatments for hepatitis C infection: a fast-moving pipeline

2017 ◽  
Vol 10 (2) ◽  
pp. 277-282 ◽  
Author(s):  
Ara A. Kardashian ◽  
Paul J. Pockros
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Medical Science ◽  
Pegylated Interferon ◽  
Hepatitis C Infection ◽  
Emerging Treatments ◽  
Low Toxicity ◽  
Direct Acting ◽  
Cure Rates

Advances in the treatment of chronic hepatitis C has been one of the pinnacles of medical science in the last 25 years. The age of direct-acting antivirals (DAAs) has led to cure rates >95% with shorter duration and low toxicity regimens, thus changing the landscape of the era of pegylated interferon and ribavirin (RBV). However, there remain some challenges with these therapies as there are multiple regimens available with a fair amount of sophistication required to administer them. Treatment continues to require knowledge of prior treatment status, viral genotype and fibrosis assessment, thus affording an opportunity for improvement in future regimens. This update reviews some upcoming therapies for the treatment of chronic hepatitis C.

Trends in the Treatment of Chronic Hepatitis C Virus Infection

2009 ◽  
Vol 22 (4) ◽  
pp. 405-418 ◽  
Author(s):  
Jennifer J. Kiser
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Liver Disease ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Standard Of Care ◽  
New Drugs ◽  
Current Standard ◽  
Course Of Illness ◽  
Chronic Hepatitis C Virus

Despite reductions in the incidence of new hepatitis C virus infections, infections from previous decades continue to place a substantial burden on our health care system. Although the course of the disease is highly variable, approximately 20% to 30% of patients develop cirrhosis, end-stage liver disease, or hepatocellular carcinoma. Fortunately, treatment with our current standard of care, peginterferon a and ribavirin, can reduce the complications of chronic liver disease. However, these drugs are associated with significant adverse effects, many patients are ineligible for treatment, and only 50% are cured. Thus, there is a tremendous need to improve our current therapies and develop new compounds for this disease. This review highlights the transmission, pathophysiology, and course of illness; the pharmacokinetics, proposed mechanisms of action, adverse events, and potential drug interactions with peginterferon a and ribavirin; current treatment trends; the role of the pharmacist in the treatment of this disease; and investigational drugs in later stages of clinical development. Despite the initial hope that these new drugs would replace our current standard of care, it has become clear that ribavirin and peginterferon a will continue to play an important role in the treatment of chronic hepatitis C virus in the years to come.

scholarly journals Pegylated interferon-alfa plus ribavirin therapies for chronic hepatitis C

2011 ◽  
Vol 51 (181) ◽  
Author(s):  
T Kanda ◽  
O Yokosuka
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Antiviral Agents ◽  
Standard Of Care ◽  
Pegylated Interferon ◽  
New Drugs ◽  
Direct Acting Antiviral ◽  
New Information ◽  
Direct Acting

Until HCV NS3/4A protease inhibitors become available at the end of 2011, the combination pegylated-interferon (PEG-IFN)-alfa and ribavirin (RBV) will remain the standard treatment for chronic hepatitis C patients. In some hepatitis C virus-infected patients, PEG-IFN plus RBV treatment against HCV should continue to be used because of side effects of new drugs such as anemia. Our Japanese experiences should provide new information for the treatment of chronic hepatitis C.  Keywords: Direct-acting antiviral agents (DAA), HCV, pegylated interferon, ribavirin, standard of care (SOC ).

scholarly journals Evolution of Interferon-Based Therapy for Chronic Hepatitis C

2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Chun-Hao Chen ◽  
Ming-Lung Yu
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Combination Therapy ◽  
Chronic Hepatitis C ◽  
Virological Response ◽  
Standard Of Care ◽  
Rapid Virological Response ◽  
Current Standard ◽  
Sustained Response Rate ◽  
Triple Combination Therapy

Since 1986, interferon-alfa (IFN-) monotherapy has been administered for patients with chronic hepatitis C (CHC). However, sustained response rate is only about 8% to 9%. Subsequent introduction of ribavirin in combination with IFN- was a major breakthrough in the treatment of CHC. Sustained virological responses (SVRs) rate is about 30% in hepatitis C virus genotype 1 (HCV-1) patients, and is about 65% in HCV-2 or -3 patients. After 2000, pegylated interferon (PegIFN) much improved the rates of SVR. Presently, PegIFN--ribavirin combination therapy has been current standard of care for patients infected with HCV. In patients with HCV-1, treatment for 48 weeks is optimal, but 24 weeks of treatment is sufficient in HCV-2 or -3 infected patients. Clinical factors have been identified as predictors for the efficacy of the IFN-based therapy. The baseline factor most strongly predictive of an SVR is the presence of HCV-2 or -3 infections. Rapid virological response (RVR) is the single best predictor of an SVR to PegIFN-ribavirin therapy. If patients can't achieve a RVR but achieve a complete early virological response (cEVR), treatment with current standard of care can provide more than 90% SVR rate. HCV-1 patients who do not achieve an EVR should discontinue the therapy. Recent advances of protease inhibitor may contribute the development of a novel triple combination therapy.

scholarly journals Evaluation of the Renal Safety of Direct Acting Antivirals in Chronic Hepatitis C Patients

2021 ◽  
pp. 34-45
Author(s):  
Islam Ashram ◽  
Mohammad Saleh
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Hcv Infection ◽  
Therapeutic Benefits ◽  
Chronic Hcv Infection ◽  
One Year ◽  
Chronic Hcv ◽  
Direct Acting ◽  
Chronic Hepatitis C Patients

Objective:Direct acting antivirals (DAA) is a class of antivirals that hasbeen extensively used in chronic hepatitis C virus (HCV) patients over the past 6 years.Despite the excellent therapeutic benefits of DAA, there is a knowledge gap regardingthe safety of this class. Several reports of possible renal toxicity associated with DAAadministration can be found in the literature. The aims of this study are: to assess therenal safety of DAA used for the treatment of chronic HCV infection and to quantify the odds ofdeveloping renaltoxicityin patients withchronicHCV viralinfection. Study Design: Disproportionalityanalysiswasusedtodetectsignalsofpotentialsideeffects. Place andDuration: Amman –Jordan,One year study since September 2017 to march 2018. Methods: The method that was applied in the current study is obtaining the data from United States (US) food and drug administration(FDA)adverseeventreportingsystem(FAERS).DatabetweenJuly,2014andSeptember,2017werecombinedandexplored.Disproportionalityanalysiswasconducted to reports from chronic HCV patients to explore possible association betweenDAA administrationand renalsideeffects. Results: This study showed that a total of 3,837,418 safety reports were available in the period between July,2014 and September, 2017. Patients with chronic HCV infection represent 22,022 cases.When considering all DAA as drug of interest, the use of DAA alone or in combinationwith interferon and/or ribavirin did not increase the risk of having renal side effects.Exploring individual DAA demonstrated a significant association between the incidenceofrenalsideeffectsandtheadministrationoftelapreviranddasabuvir.ConsideringrenalsideeffectsindividuallyshowedasignificantassociationbetweenDAAadministrationand chronickidney disease. Conclusions: In this study, we reported a significant association between DAA administration andchronic kidney disease and between telaprevir or dasabuvir and renal side effect. Thesefindings are used for hypothesis generation rather than testing.

scholarly journals Non-invasive quantification of liver fibrosis regression following successful treatment of chronic hepatitis C with direct acting antivirals

2017 ◽  
Vol 25 (4) ◽  
pp. 355-363
Author(s):  
Maria Nițescu ◽  
Cristina Vâjâitu ◽  
Oana Săndulescu ◽  
Adrian Streinu-Cercel ◽  
Daniela Pițigoi ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Liver Fibrosis ◽  
Chronic Hepatitis C ◽  
Liver Stiffness ◽  
Hcv Infection ◽  
Baseline Viral Load ◽  
Direct Acting Antivirals ◽  
Non Invasive ◽  
Direct Acting

Abstract Introduction. The past years have revolutionized the treatment of hepatitis C virus (HCV) infection, with high rates of sustained virologic response (SVR). Furthermore, liver fibrosis has recently been redefined as a dynamic, reversible process. Methods. We performed a prospective cohort study to assess the role of laboratory evaluations and non-invasive measurement of liver stiffness in establishing the right time for starting treatment and in assessing the regression of liver fibrosis in Romanian patients treated with direct acting antivirals (DAA) for genotype 1b chronic hepatitis C. Results. We present the results for 102 patients, with a mean age of 58.5 years, and a rate of SVR of 100%. Our study has ruled out older age (p=0.628), IL28B non-CC genotype (p=0.693), baseline viral load above the cutoff of 600,000 IU/mL (p=0.353), and the presence of diabetes mellitus (p=0.272) or baseline steatosis (p=0.706) as factors potentially influencing the regression of liver fibrosis following DAA treatment of HCV infection with the 3D regimen. The quantitative regression of liver stiffness was inversely correlated with the duration of HCV infection (p=0.017), suggesting that timely treatment might associate better outcomes in terms of liver fibrosis. Conclusion. Our study’s results point towards the need to start DAA treatment earlier in patients with HCV infection.

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