Antiviral therapy of hepatitis C in 2014: do we need resistance testing?

The treatment of chronic hepatitis C has fundamentally changed since the approval of the first direct-acting antivirals (DAA) in 2011. In addition to telaprevir and boceprevir, in 2014 two new NS3 protease inhibitors (simeprevir and faldaprevir), one non-nucleoside polymerase inhibitor (sofosbuvir) and one NS5a replication complex inhibitor (daclatasvir) have expanded the treatment options for chronic hepatitis C. Resistance-associated variants (RAV) are naturally produced during the HCV life cycle. The frequency of RAVs within HCV quasispecies mainly depends on their replicational fitness. Variants conferring resistance to nucleos(t)ide analogues have not been detected, and the majority of NS3 protease-resistant variants are present at low frequencies (0.1-3%) before initiation of DAA-based therapies. However, the Q80K variant conferring resistance to simeprevir has been observed in 9-48% of untreated HCV genotype 1a-infected patients, leading to reduced SVR rates. Resistant variants are detectable in the majority of patients with treatment failure to NS3 protease inhibitor- or NS5a inhibitor-based antiviral therapy. Long-term follow-up studies by population-based sequence analysis have shown the disappearance of resistant variants in the majority of patients, with median times to loss of mutations of 4-64weeks. For the nucleotide analogue sofosbuvir, the emergence of the S282T resistant variant has been observed only in single patients, with reversion to wild-type within several weeks. Data are sparse on retreatment of patients with the same DAA or the same class of DAAs. However, retreatment with a different class of DAAs after failure of NS3 protease inhibitor-based therapy has been successful in small studies. This article forms part of a symposium in Antiviral Research on "Hepatitis C: next steps toward global eradication."

Acoustic radiation force impulse imaging for evaluation of antiviral treatment response in chronic hepatitis C.

BACKGROUND AND AIMS: Antiviral therapy can stop progression of liver fibrosis and partially reverse it. Non-invasive methods have shown good diagnostic accuracies for the assessment of liver fibrosis. First studies have shown that transient elastography (TE) can be used to monitor fibrosis after antiviral therapy. Acoustic-Radiation-Force-Impulse (ARFI)-Imaging is an elastography method integrated in a conventional ultrasound machine. The aim of the present study was to demonstrate a significant difference of ARFI-values in patients with sustained-virological-response (SVR) as compared to patients without. METHOD: Ninety-eight patients infected with chronic hepatitis C virus (HCV) who had completed antiviral treatment were prospectively included in the study and received ARFI-imaging, TE and laboratory evaluation. RESULTS: Significantly lower ARFI and TE values were observed for 47 patients with SVR as compared to 51 patients without SVR (1.37 m/s vs. 2.00,p=0.0021; 4.9 kPa vs. 11.1 kPa,p<0.001), respectively. CONCLUSIONS: Liver stiffness values and shear wave velocity using ultrasound-based elastography methods are different in patients with SVR as compared to patients without SVR after antiviral therapy for chronic hepatitis C. However, the causes of this difference (fibrosis regression, cytolysis, baseline fibrosis) remain unclear and require further evaluation in future studies.