Chronic HCV Treatment After NS5A Treatment Nonresponse

Hepatitis C written on chalkboard
Retreatment for nonstructural protein 5A (NS5A) treatment nonresponse was effective and well-tolerated in both noncirrhotic and compensated cirrhotic groups.

For patients with hepatitis C virus (HCV) genotype-4 infection, retreatment for nonstructural protein 5A (NS5A) treatment nonresponse was effective and well-tolerated in both noncirrhotic and compensated cirrhotic groups. This is according to data published in the European Journal of Gastroenterology & Hepatology.

Although NS5A-based treatment regimens have demonstrated efficacy and safety, and are the standard of care in some regions, retreatments for NS5A nonresponse are limited. Therefore, investigators aimed to provide real-life data regarding retreatments after treatment nonresponse of this important regimen in patients with genotype-4 HCV infection.

To do this, 524 patients with HCV with a mean age of 48±11 years, 71% of whom were men, were recruited. Of these, 450 had nonresponse to sofosbuvir + daclatasvir and 74 to sofosbuvir/ledipasvir. Patients were then treated in 2 groups (1 with sofosbuvir + ombitasvir/paritaprevir/ritonavir + ribavirin and the other with sofosbuvir + simeprevir + daclatasvir + ribavirin), with 278 and 246 in each group, respectively.

Sustained virologic response at 12 weeks was 95.2% (95% CI, 93.3%-97.1%) overall. Sustained virologic response at 12 weeks in the 2 groups was 94.9% (95% CI, 92.5%-97.4%) for the sofosbuvir + ombitasvir/paritaprevir/ritonavir + ribavirin group and 95.5% (95% CI, 92.8%-98%) for those receiving sofosbuvir + simeprevir + daclatasvir + ribavirin. For patients with liver cirrhosis, Sustained virologic response at 12 weeks for the 2 groups were 96.4% (95% CI, 90.7%-100%) and 98% (95% CI, 94.9%-100%), respectively. The number of relapses in each group was 14 and 11, respectively.

In the sofosbuvir + ombitasvir/paritaprevir/ritonavir + ribavirin group, 3 patients developed hepatic encephalopathy, hematemesis, lower limb edema, and 1 patient died. In the other group, 3 patients developed hepatocellular carcinoma and 1 patient died. There were no cases of treatment discontinuation due to anemia.

The study was limited by the lack of patients who developed virologic nonresponse and subsequent resistance analysis. The study also did not perform double liver biopsy before and after treatment as a reference to document fibrosis changes. Instead, FIB-4 was used as a noninvasive method to compensate for liver biopsies.

One study strength was unifying the groups of patients with virologic failure to NS5A treatment, those receiving sofosbuvir + daclatasvir, and sofosbuvir/ledipasvir. Treatment with sofosbuvir/ledipasvir is still recommended by international guidelines, whereas combination sofosbuvir + daclatasvir is not. The latter does occur, however, in several smaller economy countries due to cost and effectiveness for mass treatments.

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Overall, the investigators concluded that the 2 regimens tested here are effective and tolerable in patients with NS5A virologic failure and genotype-4 HCV infection. The sustained virologic response was similar for both cirrhotic and noncirrhotic group of patients, and no difference was observed in terms of adverse effects. Investigators added that although this study did not specifically include new regimes such as sofosbuvir + velpatasvir + voxilaprevir, compared with published results, the tested regimens showed similar effectiveness and safety.


El-Khayat H, Kamal EM, Mahmoud H, et al. Retreatment of chronic hepatitis C virus genotype-4 patients after non-structural protein 5A inhibitors’ failure: efficacy and safety of different regimens. Eur J Gastroenterol Hepatol. 2020;32:440-446.