Hepatitis C: Let's Get 'Real'

Digestive Disease Week (DDW) 2016

William F. Balistreri, MD


June 24, 2016

In This Article

Efficacy and Impact of Treatment

Practice-based individual treatment outcomes may differ from those obtained in highly selected patients participating in phase 3 clinical trials. Thus, it is important to understand the real-world efficacy, safety, and benefits of various regimens used to treat HCV infection in a broad spectrum of patients.

Real-World Effectiveness of Various Regimens

Kowdley and colleagues[1] reported data from six diverse real world populations and one postmarketing investigator-sponsored clinical trial. The overall SVR12 rate was 97%. There was no significant impact of HCV genotypes or subtypes, prior treatment history, presence or absence of cirrhosis, high viral load (> 6 million), or HIV/HCV coinfection. Specifically, ledipasvir/sofosbuvir (LDV/SOF) coadministered for 8 weeks yielded high SVR rates that were consistent with phase 3 clinical trial results. These outcomes support the use of an 8-week course of LDV/SOF in treatment-naive, noncirrhotic patients with HCV genotype 1 and a baseline viral load < 6 million.

Dieterich and colleagues[2] also examined a real-world population to assess SVR12 rates in HCV genotype 1 patients who were coinfected with HIV-1 and treated with LDV/SOF with or without ribavirin for 8, 12, or 24 weeks. Data were collected from providers and specialty pharmacies through the Trio Health Innervation Platform, a cloud-based disease management program. Fifty-nine percent of patients were treated at a community site, 46% were HCV treatment-experienced, 35% had cirrhosis, and 22% had a baseline viral RNA of 6 million IU/mL or greater. Only 6% of patients were treated for 8 weeks, 74% received 12 weeks of therapy, and 20% received 24 weeks of treatment. The overall SVR12 rate from this heterogeneous population was 98%. Of the three patients who did not achieve SVR12, only one was a virologic failure. SVR rates did not differ significantly among those with a history of prior HCV treatment, cirrhosis, or duration of therapy.

Backus and colleagues[3] assessed the comparative effectiveness of LDV/SOF ± ribavirin and ombitasvir/paritaprevir/ritonavir + dasabuvir (OPrD) ± ribavirin in patients with HCV genotype 1 who were treated in routine medical practice. This observational intent-to-treat cohort used the Veterans Affairs' Clinical Case Registry to identify 6961 patients who initiated therapy for 8 or 12 weeks with LDV/SOF ± ribavirin or 12 weeks with OPrD ± ribavirin at 126 facilities. SVR rates were 91% for LDV/SOF recipients overall, 90% for LDV/SOF + ribavirin recipients, 95% for OPrD recipients, and 87% for OPrD + ribavirin recipients. SVR in those with higher degrees of fibrosis (FIB-4 > 3.25) was 87% for LDV/SOF recipients, 88% for LDV/SOF + ribavirin, 93% for OPrD, and 86% for those who were treated with OPrD + ribavirin. In patients who completed 12 weeks of treatment, SVR rates were 94% for LDV/SOF, 92% for LDV/SOF + ribavirin, 98% for OPrD, and 95% for OPrD + ribavirin. These high SVR rates were similar to those attained in clinical trials. Reduced odds of reaching an SVR was noted for those with a high body mass index (BMI), those with prior decompensation, those receiving the OPrD + ribavirin regimen, and those who were black. These lower response rates were probably associated with early DAA discontinuation, as these predictors no longer had a significant impact on the odds of reaching an SVR in those who completed a 12-week course. A FIB-4 > 3.25 remained a significant negative predictor.

Genotype 4 Chronic Hepatitis C Infection

HCV genotype 4 represents approximately 13% of HCV infections globally. Although more common in the Middle East and sub-Saharan Africa, HCV genotype 4 infection is increasingly seen elsewhere. In a phase 2b study, the ombitasvir/paritaprevir + ribavirin regimen achieved a 100% SVR12 rate in HCV genotype 4–infected participants without cirrhosis.

Asselah and colleagues[4] reported high SVR rates in HCV genotype 4–infected patients with compensated cirrhosis who were treated with ombitasvir/paritaprevir + ribavirin administered for 12 or 16 weeks. The regimen was generally well tolerated.

Ribavirin-Free Combinations

The currently approved regimen for HCV genotypes 2 and 3—sofosbuvir and ribavirin—achieves relatively good efficacy rates but at the cost of modest decrements in patient-reported outcomes (PROs). These adverse self-reported quality-of-life measures are largely related to the side effects of ribavirin.

Younossi and colleagues[5] compared PROs that were disclosed during treatment with an all-oral, fixed-dose combination of VEL/SOF vs SOF + ribavirin in patients with HCV genotypes 2 and 3. The PRO data were collected in 2 phase 3 trials of 818 patients. The SVR rates were 99% in VEL/SOF recipients with genotype 2 who were treated for 12 weeks and 95% in VEL/SOF recipients who were genotype 3; 94% in SOF + ribavirin recipients with genotype 2 who were treated for 12 weeks; and 80% in SOF + ribavirin recipients who were genotype 3 and treated for 24 weeks. By treatment week 4, 12 out of 23 PRO domains significantly improved in patients who were receiving VEL/SOF. These improvements continued to increase during treatment. In contrast, despite some improvements in various PROs by the end of treatment, decrements were noted in other PRO domains for patients in the SOF + ribavirin group.

Cirrhotic patients with HCV have a higher SVR with regimens that contain ribavirin. Younossi and colleagues[6] also compared the PROs associated with the use of ribavirin-containing regimens (SOF or VEL/SOF) in patients with and without cirrhosis. A total of 488 patients were enrolled to receive SOF/VEL + ribavirin for 12 weeks (all genotypes) or SOF + ribavirin for 12 weeks (HCV genotype 2) or 24 weeks (HCV genotype 3). Regardless of the presence of cirrhosis, ribavirin-containing regimens were associated with a mild impairment in some aspects of PROs. Substantial improvements in PROs were found after treatment, which became more impressive with longer follow-up.

Nonadherence Diminishes Real-World SVR12

The World Health Organization has estimated that 50% of people do not take medications for chronic conditions as prescribed.[7]

Altstadt and colleagues[8] assessed the effect of DAA nonadherence on SVR at 12 weeks after completion of HCV therapy and identified predictors of nonadherence. Patients who missed more than an average of one dose/month or more than five total doses were defined as nonadherent. Patients who had documented nonadherence had a 19% lower rate of SVR12 compared with those with documented adherence. SVR12 rates were 67% in the nonadherent group and 86% in the adherent group, with a 25% relapse rate in the nonadherent group. Female gender, black race, and documentation of psychiatric illness had a statistically significant association with nonadherence. Presence of commonly reported side effects (ie, fatigue, headache, nausea, diarrhea, anorexia, rash) did not significantly affect adherence.

Efforts directed at better identifying predictors of nonadherence and interventions that enhance adherence, particularly in persons with psychiatric illness, appear warranted, especially considering the financial burden of current treatment regimens.


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