Chronic HCV: Re-Treating After Nonstructural Protein 5A Inhibitors’ Failure

Hepatitis C virus (HCV). HCV causes a hepatitis that is transmitted through the blood stream (intraveinous drugs, professional exposure and nosocomial transmission). During chronic hepatitis C, cirrhosis can develop 10-20 years later, with a risk of hepatic cancer. Image produced using high-dynamic-range imaging (HDRI) from an image taken with transmission electron microscopy. Viral diameter around 22 nm. (Photo by: BSIP/Universal Images Group via Getty Images)
Investigators sought to determine whether salvage treatment for NS5A-treatment failure is effective and well tolerated in chronic HCV genotype 4-infected patients, in both noncirrhotic and compensated cirrhotic groups.

Salvage treatment for nonstructural protein 5A (NS5A)-treatment nonresponse is effective and well tolerated in patients with chronic hepatitis C virus (HCV) genotype 4 (GT4) infection with or without compensated cirrhosis, according to study results published in the European Journal of Gastroenterology & Hepatology.

NS5A inhibitor-based regimens are an important regimen for the treatment of patients with chronic HCV GT4 infection; however, re-treatment for NS5A virologic failure is limited. Therefore, researchers in Egypt aimed to provide real-life data regarding the effectiveness and safety of re-treatment with different regimens after NS5A-regimen nonresponse.

The investigators used data from 450 patients with HCV with nonresponse to sofosbuvir (SOF) + daclatasvir and 74 patients with nonresponse to SOF + ledipasvir. Patients were re-treated with SOF + ombitasvir /paritaprevir/ritonavir + ribavirin (n = 278) or SOF + simeprevir + daclatasvir+ ribavirin (n= 246).

Researchers evaluated sustained virologic response 12 weeks after the end of treatment, and found that the overall response was 95.2%: 94.9% for SOF + ombitasvir /paritaprevir/ritonavir + ribavirin and 95.5% for SOF + simeprevir + daclatasvir+ ribavirin. Patients with compensated liver cirrhosis showed similarly high sustained virologic responses at 12 weeks of 96.4% and 98%, respectively. The overall relapse rate was 4.8% (5.1% for SOF + ombitasvir /paritaprevir/ritonavir + ribavirin and 4.5% for SOF + simeprevir + daclatasvir+ ribavirin).

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No serious adverse events led to treatment discontinuation or death. It is important to note that this study did have its limitations, including the lack of resistance analysis for patients who developed nonresponse to treatment.

Researchers concluded that the use of SOF + ombitasvir /paritaprevir/ritonavir + ribavirin is safe, effective and tolerable in patients with NS5A [treatment nonresponsive] GT4 [HCV infection].”


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(3):440-446.