Journal of hepatology
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Cirrhotic patients are prone to develop life-threatening complications that require emergency care and ICU admission. They can present specific decompensations related to cirrhosis such as variceal bleeding and hepatorenal syndrome (HRS) or other critical events also observed in the general population such as severe sepsis or septic shock. Clinical management of all these entities requires a specific approach in cirrhosis. ⋯ Cirrhotic patients are also at a high risk for development of other bleeding complications and are more susceptible to nosocomial infections. This extreme complexity of critically-ill cirrhotic patients requires a specific medical approach that should be known by general intensivists since it has a negative impact on patient prognosis. This review will focus on the diagnostic approach and treatment strategies currently recommended in the critical care management of patients with cirrhosis.
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Resolution of the three-dimensional structures of several hepatitis C virus (HCV) proteins, together with the development of replicative cell culture systems, has led to the identification of a number of potential targets for direct-acting antiviral (DAA) agents. Numerous families of drugs that potently inhibit the HCV lifecycle in vitro have been identified, and some of these molecules have reached early to late clinical development. Two NS3/4A protease inhibitors, telaprevir and boceprevir, were approved in Europe and the United States in 2011 in combination with pegylated interferon (IFN)-α and ribavirin for the treatment of chronic hepatitis C related to HCV genotype 1, in both treatment-naïve and treatment-experienced patients. ⋯ They include second-wave, first-generation, and second-generation NS3/4A protease inhibitors, nucleoside/nucleotide analogue inhibitors and non-nucleoside inhibitorsof HCVRNA-dependent RNA polymerase, inhibitors of nonstructural protein 5A (NS5A) and host-targeted compounds, such as cyclophilin inhibitors and silibinin. The proof of concept that IFN-free regimens may lead to HCV eradication has recently been brought. However, new drugs may be associated with troublesome side effects and drugdrug interactions, and the ideal IFN-free DAA combination remains to be found.