Combination DAA Drug Regimen Safe, Effective for HCV-Related Cirrhosis

Antonio Ascione, MD

A new study demonstrated that a direct-acting antiviral drug (DAA) combination consisting of once-daily ombitasvir/paritaprevir plus ribavirin and twice-daily dasabuvir is a safe and effective treatment strategy for patients older than 65 years with compensated cirrhosis and/or hepatitis C (HCV) genotype-1 (GT1) infection.

The side effects to this regimen in this patient population have been proven to be mild or moderate across a global patient population, Antonio Ascione, MD, of the Centre for Liver Disease, Buon Consiglio-Fatebenefratelli Hospital in Naples, Italy, told MD Mag.

“As far as efficacy is concerned, the result is excellent because the sustained virological response (SVR) was 95%,” Ascione said.

Data were obtained from the Italian ABACUS study group, which was comprised of patients with GT1 or 4 HCV-related cirrhosis who were also at risk for decompensation (n = 240). In this study group, researchers administered 25 mg/150 mg/100 mg doses of the pharmacokinetic enhancer ritonavir in addition to once-daily ombitasvir/paritaprevir as well as twice-daily dasabuvir at 250 mg per dose and ribavirin.

Treatment duration lasted approximately 12 weeks (GT1b) and 24 weeks (GT1a). The primary endpoints for the study were treatment-related safety and efficacy outcomes. Study investigators defined efficacy as patients achieving an HCV RNA negative diagnosis approximately 12 weeks following treatment end (SVR12).

Almost one-third of study participants reported any adverse event (30.8%), yet only a small proportion of patients in the entire cohort discontinued treatment (5.4%). In the multivariable analysis, the researchers found that the baseline patient-specific variables independently associated with the occurrence of adverse events included hypertension (odds ratio [OR] 4.6; 95% CI; 2.3 - 9.2; P&thinsp;< 0.001) and albumin <3.5 g/dL (OR 2.04; 95% CI; 1.0-4.2; P&thinsp;< 0.05).

Additionally, a baseline bilirubin of <2 mg/dL was independently associated with the primary efficacy endpoint of SVR12 (OR 4.9; 95% CI; 1.17 - 20.71; P&thinsp;= 0.029).

In regard to the clinical implications, the study showed that elderly patients with cirrhosis may be considered for this combination of DAAs. However, Ascione added, careful assessment of patients’ hepatic functional status must be performed.

“In fact, in patients with reduced hepatic function, belonging to Class B of the classification most used in clinical practice, SVR is significantly reduced,” Ascione said.

In addition, Dr. Ascione stated that there are currently other DAA drugs that have “slightly higher efficacy [and] are easier to handle for compliance purposes.” For instance, these other medications may require much shorter treatment durations and may often consist of only 1 daily tablet in most cases.

For future research, it may be necessary, above all, “to evaluate if the SVR in elderly patients and with advanced cirrhosis represents an adequate marker for the evolution of the natural history of HCV infection in these patients.”

“And this is the most interesting topic on which to work, because the question is: Does the eradication of the HCV in cirrhotic patients with advanced disease change the natural history of the disease?” Ascione said.

Researchers concluded greater analysis is needed to answer this question.

The study, "Ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin for patients with hepatitis C virus genotype 1 or 4 infection with cirrhosis (ABACUS): a prospective observational study," was published online in The Lancet.