Clinics and Research in Hepatology and Gastroenterology
Mini reviewHepatitis C virus and lipids in the era of direct acting antivirals (DAAs)
Section snippets
Factors associated with response to peginterferon-α + ribavirin and triple therapy
Host and viral factors known to be associated with response to PR alone and combination triple therapy with boceprevir and telaprevir in treatment naïve and experienced patients with HCV-genotype 1 infection are summarised in the table. Data on factors associated with SVR in response to boceprevir and telaprevir has been reported from post hoc analyses of the landmark phase 3 trials in treatment naïve (Sprint-2 [9], Advance [10], Illuminate [11]) and PR treatment experienced (Respond-2 [12],
Why is low-density lipoprotein cholesterol favourable to treatment response?
The continued association of LDLC and treatment outcome to triple therapy (PR + DAAs) implies that factors involved in regulation of plasma LDLC concentrations affect the interaction of HCV and the host. These interactions may occur at the stages of entry, replication, assembly or remodelling in the vascular compartment. The major steps of the HCV lifecycle have been unravelled by experiments utilising Japanese Fulminant Hepatitis virus 1 (JFH1), a genotype 2a strain of HCV that is able to
Hepatitis C virus association with lipoproteins in the vascular compartment
HCV particles in the circulation are associated with lipoproteins. Association with lipoproteins of varying triglyceride and cholesterol composition determines the density distribution of HCV RNA in plasma [41]. HCVcc particles of low-density have higher specific infectivity in vitro [31], [42]. Low-density HCV particles associated with apoB containing lipoproteins (VLDL, IDL, LDL) have been termed ‘lipoviral particles’ (LVP) [43], [44]. We have shown that levels of LVP (HCV RNA at density < 1.07
Hepatitis C virus-genotype specific differences in lipid metabolism
It is apparent that there are HCV-genotype specific differences in lipid and metabolic phenotypes between HCV-genotypes 1 and 3. HCV-genotype 3 in particular is associated with low LDLC, apoB and hepatic steatosis, thought to be due to viral inhibition of microsomal triglyceride transfer protein (MTP) [53]. Our data supports reduced endogenous cholesterol synthesis in both HCV-genotype 1 and genotype 3. However, in HCV-genotype 3 there is evidence of selective preservation of desmosterol, and
Clinical studies of lipid modulation in hepatitis C virus
A number of retrospective and prospective studies have shown an association of increased LDLC and favourable response to PR therapy [8], [58]. In HCV-genotype 1 infection, statins have shown limited antiviral efficacy when used as monotherapy [59], [60], [61], [62], [63], although in small numbers appear well tolerated [64]. Statin use in combination with PR may improve outcome. In a retrospective study of US veterans [65], statin use in diabetics and non diabetics was associated with increased
Conclusions
The intimate interaction of HCV and lipid pathways continues to provide possible therapeutic avenues in the post DAA era, because of the association of lipids with interferon sensitivity. Remarkably LDLC and statin use are associated with favourable outcomes in the phase 3 DAA trials. Further data of factors associated with non-response to DAAs in ‘real world’ use needs to be reported. A mass of in vitro data emphasises the importance of lipid metabolism to the viral lifecycle, and there are
Disclosure of interest
The authors declare that they have no conflicts of interest concerning this article.
Funding: Funding supported by the Medical Research Council (G0502028) and the Newcastle upon Tyne Healthcare Charity.
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Lipid kinetics during dual antiviral therapy in patients with chronic hepatitis C
2015, Medicina ClinicaPCSK9, apolipoprotein e and lipoviral particles in chronic hepatitis C genotype 3: Evidence for genotype-specific regulation of lipoprotein metabolism
2015, Journal of HepatologyCitation Excerpt :Our finding emphasises the link between HCV-G3 replication, steatosis, viral load, and LDL-C. This suggests that LDL-C should be included in the parameters examined as predictors of virological relapse in the era of direct acting antivirals [41]. The poor correlation between viral load and disease severity in chronic HCV could be partially explained by the increasing evidence that not all of the HCV RNA is equally infectious.
Lipids in innate antiviral defense
2013, Cell Host and MicrobeCitation Excerpt :In particular, statins are generally well tolerated in patients and have broad-spectrum antiviral activity in vitro. Accumulating evidence suggests that they have some efficacy in treating HCV and IAV infections, either via antiviral activity or immunomodulatory effects (reviewed in Sheridan et al., 2013; Walsh, 2012). As the discoveries of these antiviral mechanisms that primarily target fusion are quite recent, many questions and exciting avenues for research remain.
Statin therapy improves response to interferon alfa and ribavirin in chronic hepatitis C: A systematic review and meta-analysis
2013, Antiviral ResearchCitation Excerpt :The recent focus in anti-HCV therapy is mainly on the development of combination therapies containing different DAAs without interferon and/or ribavirin. However, low density lipoprotein cholesterol and statin use are still considered to be important associations of outcome with DAAs and the interactions of HCV and host lipid metabolism are still believed to play a relevant role in the era of DAAs for chronic hepatitis C (Sheridan et al., 2012). In view of this, statins may, at least in some respects, have an irreplaceable role in the successful treatment of chronic hepatitis C. Furthermore, in vitro studies have showed that statins increase the antiviral activity of different DAAs in an additive manner and delay or even prevent the development of resistance against DAAs (Delang et al., 2009).
Impact of NAFLD on the outcome of patients with chronic hepatitis B in Asia
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