CLDs represent an important, and certainly underestimated, global public health problem. CLDs are highly prevalent and silent, related to different, sometimes associated causes. The distribution of ...the causes of these diseases is slowly changing, and within the next decade, the proportion of virus‐induced CLDs will certainly decrease significantly while the proportion of NASH will increase. There is an urgent need for effective global actions including education, prevention and early diagnosis to manage and treat CLDs, thus preventing cirrhosis‐related morbidity and mortality. Our role is to increase the awareness of the public, healthcare professionals and public health authorities to encourage active policies for early management that will decrease the short‐ and long‐term public health burden of these diseases. Because necroinflammation is the key mechanism in the progression of CLDs, it should be detected early. Thus, large‐scale screening for CLDs is needed. ALT levels are an easy and inexpensive marker of liver necroinflammation and could be the first‐line tool in this process.
Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are among the most frequent viral infections in humans, and represent a major global public health problem. HBV‐ and HCV‐related chronic ...hepatitis are the main causes of cirrhosis and hepatocellular carcinoma (HCC) that are responsible for a high rate of morbidity and mortality. End‐stage HBV‐ and HCV‐related liver disease and HCC are the main causes of liver transplantation. In the last few years, knowledge of the epidemiology and the natural history of HBV and HCV infection has markedly improved. Furthermore, considerable progress has been made in the efficacy of therapy. New drugs and new therapeutic strategies that are currently under evaluation could further improve the efficacy of therapy in the near future.
For HCV infection, there have been major advancements during last several years with large numbers of ongoing trials with various direct‐acting antivirals (DAA) showing high potency, favourable ...tolerability profile, higher barrier to resistance, shortened treatment duration, all oral regimen, pan‐genotypic, fewer drug interactions and reduced pill burden. By 2014, several DAAs are anticipated to complete successful phase III trials and will be commercially available. Initially, a wave of IFN‐based regimen (sofosbuvir, faldaprevir and simeprevir) will be available for treatment of HCV genotype 1. In the near future, combination of antiviral agents with additive potency that lack cross‐resistance with good safety profile will likely be the new recommended regimens, making HCV, the first chronic viral infection to be eradicated worldwide with a finite duration of combination DAA therapy without IFN or ribavirin. The aim of this review was to summarize the results obtained from recent DAA combination studies without IFN.
Chronic hepatitis C is one of the leading causes of chronic liver disease with approximately 170 million people infected worldwide. Sustained virological response (SVR) is equivalent to viral ...eradication and associated with a reduction in the risk of cirrhosis. Nowadays the treatment for hepatitis C virus (HCV) genotype 1 chronic infection is the addition of direct acting antivirals (DAA) with a protease inhibitor (telaprevir or boceprevir) to the pegylated interferon (PEG‐IFN) plus ribavirin (RBV) regimen. The future management of patients with these new molecules will require good clinical practice, knowledge of indications, management of side effects and monitoring for antiviral resistance. Certain major medical needs are still unmet and require studies in special populations (HIV‐HCV coinfected patients, transplanted patients, etc.…) and also in HCV non‐1 genotype patients and in non‐responders. Second generation DAA are in development. Combinations of antivirals with additive potency that lack cross resistance and with a good safety profile may provide new regimens in the future to make HCV the first chronic viral infection eradicated worldwide with a finite duration of combination DAA therapy without IFN. The aim of this review is to summarize mechanisms of action and results obtained with DAAs.
There has been a revolution in the treatment of chronic hepatitis C. Several oral regimens combining direct‐acting antivirals (DAAs) from different families NS5B nucleotide inhibitors, NS5B ...non‐nucleoside inhibitors, NS5A replication complex inhibitors and NS3/4A protease inhibitors (PI) have been developed. These regimens result in an increase in sustained virological response (SVR) rates to above 90% and reduce the duration of treatment to 12 weeks or less. As of 2016 several regimens will be approved with additive potencies, without cross‐resistance and with a good safety profile. Remaining issues will include increasing screening and access to care so that HCV may become the first chronic viral infection eradicated worldwide. This review summarizes results obtained with oral DAA combinations that have been approved and/or have completed phase 3 clinical trials for HCV infection and discusses future perspectives.
Chronic hepatitis C is one of the leading causes of chronic liver disease, with approximately 170 million people infected worldwide. The severity of disease varies from asymptomatic chronic infection ...to cirrhosis and hepatocellular carcinoma (HCC). Sustained virological response (SVR) is long lasting, associated with a reduced risk of cirrhosis and HCC. In the near future, standard of care (SOC) treatment of hepatitis C virus (HCV) will include the addition of direct‐acting antivirals (DAAs) with a protease inhibitor to the pegylated interferon (PEG‐IFN) plus ribavirin (RBV). In HCV genotype 1 patients, promising results have been reported when the protease inhibitor telaprevir or boceprevir is added to the SOC, increasing SVR rates from less than 50% (PEG‐IFN plus RBV) to 70% (in patients treated with a triple combination of PEG‐IFN, RBV plus a protease inhibitor). The future management of patients with these new molecules will require good clinical practice, knowledge of indications, prediction of side effects and monitoring for antiviral resistance. Certain major medical needs are still unmet, requiring studies in special populations (human immunodeficiency virus–HCV‐coinfected patients, transplanted patients, etc.) in genotype non‐1 patients and in absolute non‐responders. Combinations of antivirals with additive potency that lack cross resistance and with a good safety profile may provide new regimens in the future to make HCV the first chronic viral infection eradicated worldwide with a finite duration of combination DAA therapy without IFN. There is ongoing development of new molecules such as HCV enzyme inhibitors. The aim of this review is to summarize the results obtained with DAAs: protease and polymerase inhibitors.
Summary HCV infection is a global health problem that affects 170 million people worldwide. The severity of the disease varies from asymptomatic chronic infection to cirrhosis and hepatocellular ...carcinoma (HCC). Recently, the standard of care for genotype 1 patients has greatly improved with the addition of protease inhibitors (telaprevir or boceprevir) to pegylated interferon (PegIFN) and ribavirin (RBV). The prediction of fibrosis progression and the response to antiviral treatment are two major issues in the management of patients with chronic hepatitis C. Differential expression of mRNAs was first analyzed for both progression of fibrosis and treatment response. Specific polymorphisms, associated with either fibrosis or viral response, were identified thanks to major improvements in genome scanning technologies. Since 2009, several independent genome wide association studies (GWAS) have reported an association between genetic polymorphisms within the IL-28B promoter and both natural and treatment-induced clearance in genotype 1 infected patients. These different studies showed the strong association and the importance of IL-28B polymorphisms in the treatment response. Combining the different genetic factors could improve their predictive value and help identify patients at a high risk of progression of fibrosis as well as those with a lower chance of responding to treatment. The aim of this review was to discuss the genomic factors (mRNAs, miRNAs, and SNPs) and HCV infection with clinical implications for either progression of fibrosis or treatment response. Recent findings on the IL-28B polymorphism and its application in clinical practice will also be discussed.
With the approval of second‐wave direct‐acting antivirals simeprevir, sofosbuvir and faldaprevir in 2014–2015, for genotype 1 hepatitis C, patients and doctors will have more treatment options. ...During a first period, these treatments will still be used with peginterferon and ribavirin. The second wave of IFN‐based triple therapy will have benefits and risk. These treatments have the following advantages: higher efficacy with more patient candidates for a shorten treatment duration (12–24 weeks, instead of 48 weeks). These new treatments appear to have a better safety profile than first generation, with no additional increase in anaemia over peginterferon/ribavirin. Then, these treatments are to take for patients with a decrease in pill burden (these three direct‐acting antivirals are given orally one pill a day). Simeprevir and sofosbuvir may be approved in the US and Europe, in 2014, at the time this manuscript will be released. Approval of faldaprevir will follow. These direct‐acting antivirals with many others will hopefully be combined in future interferon‐free regimens. The goal of this review to summarize the results and safety of simeprevir, faldaprevir and sofosbuvir, to advise physicians and to inform patients on the benefits and risks of these second‐wave IFN‐based regimens for HCV genotype infection.
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