Liver international : official journal of the International Association for the Study of the Liver
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Review
Phase III results of Boceprevir in treatment naïve patients with chronic hepatitis C genotype 1.
Chronic hepatitis C virus infection affects approximately 2% of the world population and can result in cirrhosis and hepatocellular carcinoma. Until 2011, the standard of care (SOC) has been therapy with pegylated interferon alfa and ribavirin (PEG-IFN/RBV). Sustained virologic response rates (SVR) after SOC in patients infected with genotype 1 have been 40-50%. The development of new direct antiviral agents (DAA) is vital. The first drugs that specifically target the HCV protease have been approved in 2011. This review summarizes the results of SPRINT-2, a phase III double blind, placebo controlled study in which the efficacy and safety of Boceprevir, a new HCV protease inhibitor, was compared to SOC. ⋯ Triple therapy of Boceprevir in combination with PEG-IFN 2b/RBV is more effective than SOC alone. RGT is possible without reducing the SVR rates. Management of anaemia has to be considered.
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Genotype 2 (HCV-2) accounts for 8% of the patients with chronic hepatitis C virus in Europe. Because of the favourable response to interferon (IFN)-based treatment, this group is considered an 'easy-to-treat' genotype along with HCV-3. However, experimental and clinical data suggest possible differences between HCV-2 and -3. ⋯ A nucleotide analogue polymerase inhibitor, PSI-7977 by Pharmasett has been shown to be active against both. The role of the IL28B polymorphism as a predictor of response to the current standard of care (SoC), PEG-IFN and RBV treatment is the subject of debate, but this mainly seems to be because of the small size of the samples in the studies performed so far. Existing results suggest that the genetic evaluation of IL28B may be useful in patients with HCV-2 for predicting response in patients without RVR.
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Acute kidney injury (AKI) has a major impact on short- and long-term survival in liver transplant (LT) patients. There is no currently accepted uniform definition of AKI, which would facilitate standardization of the care of patients with AKI and to improve and enhance collaborative research efforts. New promising biomarkers such as neutrophil gelatinase-associated lipocalin or kidney injury molecule-1 have been developed for the prevention of delayed AKI treatment. ⋯ Other strategies to overcome CNI nephrotoxicity include CNI minimization protocols or CNI withdrawal and conversion to mycophenolate mofetil or the mammalian target of rapamycin inhibitor-based immunosuppressive regimens. However, CNI avoidance may bear a higher rejection risk. Thus, more results from randomized-controlled studies are urgently warranted to determine which drug combinations are the most beneficial approaches for the potential introduction of CNI-free immunosuppressive regimens.
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Review
Future treatment of chronic hepatitis C with direct acting antivirals: is resistance important?
Recent advances in molecular biology have led to the development of novel small molecules that target specific viral proteins of the hepatitis C virus (HCV) life cycle. These drugs, collectively termed directly acting antivirals (DAA), include a range of non-structural (NS) 3/NS4A protease, NS5B polymerase and NS5A inhibitors at various stages of clinical development. Some others drugs called 'non DAA'or indirect inhibitors are not focused on one site of the life cycle target and are still in early pre-clinical and clinical phase I, II and III trials. ⋯ Information on patterns of resistance to and cross resistance between antiviral agents is increasingly available and may be important for decisions on how to combine drugs to achieve an optimum antiviral effect. This review debates the clinical relevance of resistance to direct and indirect inhibitors taking into account the future potential therapeutic strategies to help patients who do develop resistance to HCV inhibitors. Finally, this chapter treats two points of view: 'for' and 'against' the question of the importance of resistance.