[Show abstract][Hide abstract] ABSTRACT: Chronic hepatitis C virus (HCV) infection is responsible for the development of liver cirrhosis and hepatocellular carcinoma. It has been a tremendous burden on global health care systems. With the advent of a number of new direct-acting and host-targeting antiviral agents, current interferon-α- and ribavirin-based HCV therapy has started to move towards an interferon-sparing or even interferon-free strategy. In this regard, a recently identified NS5A inhibitor, daclatasvir, showed a great promise in clinical trials as another new class of direct-acting anti-HCV therapeutics, with a distinct mechanism of action. In this review, a variety of preclinical as well as clinical proof-of-concept studies of daclatasvir, including the studies of its discovery, mechanism of action, viral resistance, and host polymorphism profiles are reviewed. In addition, a role of daclatasvir in the future therapy for HCV patients is discussed briefly.
Drug Design, Development and Therapy 01/2013; 7:1223-1233. · 3.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cirrhosis affects millions of people throughout the world. Two of the most serious complications of liver cirrhosis are ascites and spontaneous bacterial peritonitis (SBP). The development of ascites is related to the severity of portal hypertension and is an indicator of increased mortality. Although sodium restriction and diuretic therapy have proven effective, some patients may not respond appropriately or develop adverse reactions to diuretic therapy. In such cases, interventions such as transjugular intrahepatic portosystemic shunt (TIPS) placement are warranted. SBP is a complication of ascites that confers a very high mortality rate. Recognition and prompt treatment of this condition is essential to prevent serious morbidity and mortality. Initiation of prophylaxis in SBP remains controversial. Given the burden of liver cirrhosis on the health care system, ascites and SBP will continue to provide challenges for the primary care provider, hospitalist, internist, and gastroenterologist alike.
Saudi Journal of Gastroenterology 09/2014; 20(5):279-287. · 1.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Most direct-acting antivirals (DAAs) being developed against the hepatitis C virus target the NS3/4A protease, the NS5A protein and the NS5B polymerase. The latter enzyme offers different target sites: the catalytic domain for nucleoside/-tide analogues as well as a number of allosteric sites for non-nucleoside inhibitors. Two NS3/4A protease inhibitors have recently been approved and more than 40 new NS3/4A, NS5A or NS5B inhibitors are in the development pipeline. These agents can achieve very high cure rates when combined with pegylated-interferon-α and ribavirin and show promising clinical results when combined in all-oral combinations. In addition to the more canonical drug targets, new alternative viral targets for small-molecule drug development are emerging, such as p7 or NS4B and viral entry. Future research will need to define well-tolerated and cost effective DAA combinations, providing the highest rates of viral eradication in all patients, including those with advanced liver disease, with broadest spectrum of action on viral genotypes, showing minimal or no clinical resistance and with the shortest treatment duration. (HEPATOLOGY 2013.).
Hepatology 03/2013; · 11.19 Impact Factor
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