Liver international : official journal of the International Association for the Study of the Liver
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Inflammation is a major factor for the progression of chronic liver diseases. Interactions between urokinase plasminogen activator (uPA) and its receptor (uPAR) have been functionally linked to hepatic inflammation and fibrosis in mice. High serum concentrations of soluble uPAR (suPAR) are suggested to reflect activated immune cells. ⋯ Serum suPAR is a potential novel biomarker for the diagnosis of cirrhosis, identification of alcoholic origin and for determining prognosis in patients with chronic liver disease.
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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.