Current and Evolving Treatments of Genotype 1 Hepatitis C Virus

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Key points

  • Direct-acting antivirals (DAAs) have become standard treatment of HCV genotype 1 infection.

  • For many treatment regimens, the duration is just 12 weeks.

  • Ribavirin may provide additional efficacy for patients with cirrhosis or HCV subtype 1a infection.

  • The continued rapid development of DAAs suggests that new regimens will become available for shorter duration of therapy.

Goal of therapy

The aim of treating HCV infection is to cure the chronic viral infection, thereby preventing complications of HCV-related liver disease, including cirrhosis, hepatocellular carcinoma (HCC), and the need for a liver transplant. Cure from HCV infection can be measured by SVR,13, 14 which is defined as the absence of HCV RNA by polymerase chain reaction after cessation of antiviral therapy. Classically, SVR was measured 24 weeks after stopping therapy, but the FDA has accepted the absence of HCV

Patient evaluation overview

Routine laboratory evaluation and assessment of the degree of fibrosis, mostly by noninvasive measures, are extremely important to prioritize patients for treatment and to determine the appropriate treatment regimen and duration. According to the HCV guidance from the American Association for the Study of Liver Diseases (AASLD)/Infectious Diseases Society of America (IDSA), patients with advanced fibrosis, cirrhosis, or with extrahepatic complications of HCV have priority for treatment compared

Treatment options

The current HCV treatment guidelines from a joint collaboration of the AASLD, IDSA, and International Antiviral Society USA (IAS-USA)17 and from the European Association for the Study of the Liver16 include later-generation DAAs in their recommendations for treatment of genotype 1 infection. Summarized versions of these guidelines can be seen in Table 2, Table 3, Table 4. Updated and detailed versions of the guidelines should be accessed on their respective Web pages (//www.HCVguidelines.org

Drug interactions

A summary of drug interactions from the AASLD/IDSA/IAS-USA guidelines17 is presented in Table 6.

Monitoring during therapy

Response guided therapy, which was standard of care for interferon-based regimens, is not applicable with all-oral treatment regimens for HCV genotype 1 infection. All-oral treatments of HCV genotype 1 infection are highly effective; data from clinical trials indicate that in 95% to 100% of patients with HCV genotype 1 infection, HCV RNA becomes undetectable during treatment. Virologic failure because of drug resistance is extremely rare. Patients who do not achieve SVR usually experience

Safety of direct-acting antivirals

As interferon-based regimens become less common, the complications due to treatment have decreased, and tolerance of current all-oral regimens is excellent.48 However, ribavirin is associated with adverse hematologic events, fatigue, rash, sinusitis, and gout.49 Ribavirin is also contraindicated for patients with a history of significant cardiac disease and in women who are pregnant because of significant teratogenic and embryocidal effects.50 That said, even with ribavirin included, all-oral,

Future therapy

Several novel DAAs for HCV are in clinical development, making it likely that treatment outcomes for patients with genotype 1 HCV infection will continue to improve.

In the C-WORTHY phase 2 study, HCV genotype 1–infected treatment-naive patients with cirrhosis (cohort 1) and treatment-experienced patients without cirrhosis (cohort 2) received 12 or 18 weeks of grazoprevir (NS3/4A protease inhibitor) and elbasvir (an NS5A inhibitor) with or without ribavirin. SVR12 rates ranged from 90% (28 of

Summary

In the past 2 years, the HCV therapeutic landscape has shifted from difficult-to-tolerate regimens with low rates of response to shorter, better-tolerated, all-oral regimens with rates of SVR greater than 95%. As more DAAs are approved for use in patients, the focus for future clinical trials will be on treating various patient populations, such patients with advanced fibrosis, post–liver transplant patients, and patients with kidney disease.

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    Potential Conflict of Interest: The authors consults for and received grants from AbbVie, Bristol-Myers Squibb, Gilead, Janssen, and Merck.

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