Treating Hepatitis C Virus: How the Standard of Care is Evolving
Hepatitis C virus (HCV), a major epidemic affecting an estimated 150 million people worldwide, is responsible for more than 350,000 annual deaths from HCV-related liver diseases.1
Since 1982, the incidence of acute HCV infection in the United States has declined,2 due primarily to HCV screening in transfusion centers and universal health care precautions in health care settings.2 However, the number of patients with complications of chronic HCV is increasing—a trend that is expected to continue.2
HCV differs from other viral infections in that it can be cured with antiviral therapy because HCV nucleic acids are not integrated into the host genome, nor is there a viral latency phase.2 Current anti-HCV approaches seek to cure the infection, thereby preventing HCV-related complications and potential contagion to others.
The Evolving Standard of Care
In the 1990s, interferon (IFN) alpha-2a, IFN alpha-2b, and IFN alfacon-1 were the foundation of HCV treatment. A significant breakthrough occurred in 1998 when ribavirin (RBV), a synthetic guanosine analogue, was approved, used in combination with IFN, and found to significantly improve sustained virologic response (SVR).3
A further development, pegylated interferon (PegIFN), prolonged the IFN half-life, allowing for once-weekly dosing and improved pharmacokinetic profiles.3 Combination of ribavirin with once-weekly injectable PegIFN over a 24- to 48-week period yielded significant increase in genotype nonspecific SVR (approximately 55%)3—a dramatic improvement over previous regimens—and became the standard of care.2
However, this regimen was deficient in several areas. It yielded a low SVR in genotype 1 and poor response rates in certain subpopulations, and patients experienced side effects.2
In 2011, two direct-acting antivirals (DAAs)—telaprevir and boceprevir—were approved for treatment of HCV, to be used in conjunction with RVC and PegIFN-alpha. This triple therapy "ushered in a new era of HCV treatment."4 These agents target specific genomic pathways that interfere with HCV infection and replication.2
Telaprevir is a selective inhibitor of NS3/4A protease, a serine protease cofactor that plays an important role in HCV replication.5 Boceprevir is a "potent ketoamide inhibitor of HCV NS3 serine protease."5 Triple therapy has been shown to significantly raise SVR rates.5
Underuse of Triple Therapy
Despite its documented efficacy, triple therapy is underused in clinical practice.
Chen et al4 performed a retrospective cross-sectional study of 487 patients with HCV genotype 1 infection to compare features of patients treated with triple therapy to those who deferred it, over a nine-month period, shortly after the FDA's approval of boceprevir and telaprevir.
The majority of patients were 50 to 60 years old, male, non-Hispanic white, and married. About half the patients were treatment-naïve, while the other half had been previously treated. The majority had advanced fibrosis, with close to 20% displaying complications of liver disease.
Only 91 patients (18.7%) began treatment with triple therapy, and 396 patients remained untreated. The low number of patients initiating therapy remained constant throughout the study period.
The researchers suggested several provider- and patient-specific reasons for treatment deferral. Most of the patients had relative contraindications to treatments, such as complications of liver disease and medical comorbidities. A history of significant side effects during previous treatment was the third most common contraindication.
Additionally, more than 15% of patients had mild liver disease, suggesting that potent therapy might be unnecessary or premature. A tenth of patients (of whom 76% had at least moderate liver fibrosis) were recommended to wait for future treatment options.
Lastly, more than one-fifth of patients declined treatment because of concerns about side effects, limited success rates, financial issues, or inability to commit time for treatment.4