Elbasvir/Grazoprevir: First-Line Therapy for Chronic HCV in DAA-Naive Patients?

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Researchers found data that showed that in patients who were direct-acting antiviral treatment- naive the nonstructural protein 5A inhibitor elbasvir combined with the NS3/4A protease inhibitor grazoprevir is safe and effective for hepatitis C genotype 1 infection, having a sustained viral response at 12 weeks post-treatment. They also noted that this should be a first-line treatment.

Elbasvir (EBR) combined with grazoprevir (GZR) may be extremely useful as first-line therapy for chronic hepatitis C virus (HCV) infection in patients who are direct-acting antiviral (DAA) treatment-naive, according to retrospective study results published in Hepatology Research.1

Patients with chronic HCV infection are at high risk for developing cirrhosis, liver failure, and hepatocellular carcinoma (HCC); therefore early eradication of HCV is desirable.2-8 Combination therapy with the NS5A inhibitor, EBR, and the NS3/4A protease inhibitor, GZR, has demonstrated a high sustained viral response at 12 weeks post-treatment rate (SVR12)  in patients with chronic HCV and cirrhosis (96.5% and 97.1%, respectively), and unlike other therapies, may be safely used in patients with renal dysfunction, including comorbid chronic kidney disease.9-12

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Researchers associated with the Japanese Red Cross Liver Study Group investigated the outcomes and safety of EBR/GZR treatment, along with its efficacy in patients who did not respond to treatment with existing DAAs.1 They found that treatment outcomes were good in patients who were DAA-naive, in that 99.4% achieved SVR. Of 353 patients, only 10 (2.9%) did not respond to treatment; of these, 8 had previously received DAA therapy and 2 had NS5A-L31/Y93 double mutation. The researchers found upon multivariate logistic regression analysis that ND5A-Y31/Y93 double mutation is an independent predictor of non-response to treatment. In addition, no serious adverse events were observed with EBR/GZR therapy.

The investigators concluded that, “EBR/GZR would have resulted in an SVR rate of 100% in patients with neither a history of DAA therapy nor a double RAS mutation. This combination of drugs could be given safely to patients and was therefore considered to be extremely useful as first-line therapy for DAA-naïve patients.”1


1. Mashiba T, Joko K, Kurosaki M, et al. Real-world efficacy of elbasvir and grazoprevir for hepatitis C virus (genotype 1): A nationwide, multicenter study by the Japanese Red Cross Hospital Liver Study Group [published online May 11, 2019]. Hepatol Res. doi:10.1111/hepr.13362

2. Asahina Y, Tsuchiya K, Nishimura T, et al. a-Fetoprotein levels after interferon therapy and risk of hepatocarcinogenesis in chronic hepatitis C. Hepatology. 2013;58:1253-1262.

3. Tanaka Y, Hanada K, Mizokami M, et al. A comparison of the molecular clock of hepatitis C virus in the United States and Japan predicts that hepatocellular carcinoma incidence in the United States will increase over the next two decades. Proc Natl Acad Sci USA. 2002;99:15584-15589.

4. Ikeda K, Saitoh S, Arase Y, et al. Effect of interferon therapy on hepatocellularcarcinogenesis in patients with chronic hepatitis type C: a long-term observation study of 1643 patients using statistical bias correction with proportional hazard analysis. Hepatology. 1999;29:1124-1130.

5. Imai Y, Kawata S, Tamura S, et al. Relation of interferon therapy and hepatocellularcarcinoma in patients with chronic hepatitis C. Ann Intern Med. 1998;129:94-99.

6. Yoshida H, Shiratori Y, Moriyama M, et al. Interferon therapy reduces the risk for hepatocellular carcinoma: national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan. Ann Intern Med. 1999;131:174-181.

7. Kasahara A, Hayashi N, Mochizuki K, et al. Risk factors for hepatocellular carcinoma and its incidence after interferon treatment in patients with chronic hepatitis C. Hepatology. 1998;27:1394-1402.

8. Ogawa E, Furusyo N, Kajiwara E, et al. Efficacy of pegylated interferon alpha-2b and ribavirin treatment on the risk of hepatocellular carcinoma of patients with chronic hepatitis C: a prospective multicenter study. J Hepatol. 2013;58:495-501.

9. Bell AM, Wagner JL, Barber KE, Stover KR. Elbasvir/grazoprevir: A review of the latest agent in the fight against hepatitis C. Int J Hepatol. 2016;2016:3852126.

10. Kumada H, Suzuki Y, Karino Y, et al. The combination of elbasvir and grazoprevir for the treatment of chronic HCV infection in Japanese patients: a randomized phase II/III study. J Gastroenterol. 2017;52:520-533.

11. Takeuchi Y, Akuta N, Sezaki H, et al. Efficacy and safety of elbasvir plus grazoprevir combination therapy in Japanese patients infected with hepatitis C virus genotype 1b. Hepatol Res. 2019;49(3):256-263.

12. Reddy KR, Roth D, Bruchfeld A, et al. Elbasvir/grazoprevir does not worsen renal function in patients with hepatitis C virus infection and pre-existing renal disease.

Hepatol Res. 2017;47:1340-1345.