Expanding the applicability of noninvasive fibrosis markers in HIV/HCV co-infected patients

Abstract

We read with interest the article by Ikeda et al. 1 The authors have elegantly shown that flavustatin, atorvastatin, and simvastatin exert a strong inhibitory effect on HCV replication in their in vitro model. Such an effect was drastically increased when these statins were used in combination with interferon-alpha. The authors report that fluvastatin exhibited the strongest anti-HCV activity, whereas atorvastatin and simvastatin showed moderate inhibitory effects. Ikeda and colleagues argue that these statins might be clinically useful in treatment of HCV infection given that they are commonly used for the treatment of hypercholesterolemia without inducing severe side effects. 1 In our opinion, evidence from basic studies needs to be translated into clinical practice with great caution. In particular, we point out that the use of HMG-CoA reductase inhibitors is likely associated with an up-regulation in LDL receptors. 2 Given that HCV is deemed to enter the hepatocytes via such LDL receptors, 3 it has been speculated that the use of drugs that lower lipid plasma levels might translate into an increased rate of HCV infection, 4 which could counterbalance in vivo the antiviral effects observed in vitro. 1 Evidence for the close interaction between beta-lipoprotein levels and HCV viremia also comes from a recent retrospective study showing that the higher the cholesterol and LDL levels prior to treatment, the greater the odds of responding to interferon-based antiviral treatment. 5 On the other hand, the inverse correlation existing between serum cholesterol levels and hepatic steatosis, which is reversible after effective antiviral treatment, 6 suggests that HCV needs fatty substrates to thrive. In the final analysis, lipid-lowering agents might translate into an enhanced entrance rate of HCV into the hepatocytes, which could be balanced by an impaired replication due to the potential "direct" antiviral action.The pharmacokinetic profile also has to be considered. The authors argue that pravastatin, the only hydrophilic statin examined in the index study, 1 enters the cells and has the same metabolic effects as the other statins. However, the physicochemical properties, which are dependent on the different chemical structures, 7 might affect both the pharmacokinetic features and antiviral properties of different HMG Co-A inhibitors. In particular, statin concentration at the level of hepatic membranes is a critical factor. As pointed out by the authors, plasma concentrations of fluvastatin during treatment with standard therapeutic dosages are lower than those expected to be effective in vitro for a synergistic effect of interferon on HCV replication. 1 This makes it very difficult to predict the drug concentration inside liver cells and thus to anticipate antiviral effects in a clinical setting.In conclusion, we suggest that the structure-activity relationship of statins may account for their kinetic and at least a part of their antiviral properties. The complexity of the interaction between HCV and lipoprotei...

Optimized cutoffs improve performance of the aspartate aminotransferase to platelet ratio index for predicting significant liver fibrosis in human immunodeficiency virus/hepatitis C virus co‐infection

“…Using these cutoffs, liver biopsy could have been avoided in 71% of the patients. We have recently contributed to the external validation of the FIB‐4 model in HIV‐HCV co‐infected patients (31). In order to expand the applicability of this index, we proposed a modified model with AST and ALT levels expressed as times the ULN.…”

Non-invasive diagnosis of liver fibrosis in chronic hepatitis C

“…The authors also showed a similar performance between FIB-4 and FibroTest ® [42] . Several other studies reported that the FIB-4 index had a variable degree of accuracy in HCVinfected subjects [43][44][45][46][47] . We performed a comparison between FIB-4 and APRI and found similar AUROCs for both models (0.811 vs 0.793) [23] .…”

Évaluation non invasive de la fibrose hépatique au cours des co-infections VIH et VHC et/ou VHB

“…Le score FIB-4 a récemment été réévalué [12] et sa performance diagnostique apparaît similaire à l'étude princeps pour le diagnostic de la fibrose sévère F3-F4 chez les co-infectés VIH-VHC [13]. Elastomé trie impulsionnelle C'est une méthode physique qui, grâce à une petite impulsion, mesure l'élasticité du foie qui est proportionnelle au degré de la fibrose hépatique [14].…”