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Anti-HCV therapy induces moderate response rates in patients with advanced liver disease

In a phase 2a trial, a combination, direct-acting antiviral therapy, consisting of Harvoni and GS-9451, induced moderate sustained virologic response rates in patients with advanced liver disease, according to a study published in Clinical Infectious Diseases. However, these moderate sustained virologic response rates were still lower than the rates found in patients without cirrhosis.

“Our study demonstrates the modest efficacy of combination DAA therapy for six weeks in a cohort of predominantly African-American patients with advanced liver fibrosis, including those with treatment experience and cirrhosis,” Sarah Kattakuzhy, MD, of the University of Maryland, and colleagues wrote. “This study supports the scientific principle that enhancing the potency of DAA regimens permits reduction in treatment duration by eliminating all HCV-infected hepatocytes. However, response rates in this investigation were lower than those observed previously in patients without cirrhosis. As such, our findings suggest that in the setting of advanced fibrosis, short duration therapy with current agents will not achieve the high rates of SVR seen in clinical trials with standard duration.”

Between April 2014 and June 2015 at the Clinical Research Center of the NIH, Kattakuzhy and colleagues enrolled fifty adult patients, all of whom had chronic HCV genotype 1 infection and stage 3 to 4 liver fibrosis. Of the patients enrolled, 60% were black and 66% were men. The fifty patients were evenly split between treatment-naïve and treatment-experienced groups, with the average age of each group being 57.3 years and 58.8 years, respectively. For 6 weeks, the patients received one dose of Harvoni  (ledipasvir 90 mg/sofosbuvir 400 mg, Gilead Sciences) and 80-mg GS-9451 daily. Patients were monitored daily for SVR until 12 weeks after treatment.

The primary efficacy endpoint was the proportion of patients with plasma HCV RNA below the lower limit of quantification, 12 weeks after treatment. “The primary safety endpoint was the frequency and severity of adverse events,” the researchers wrote.

The researchers found that 76% of patients (95% CI, 60%-85%) who received anti-HCV therapy achieved SVR 12 weeks after treatment. There was no statistically significant difference in efficacy in terms of virologic response between treatment-naïve (72%) and treatment-experienced (80%) groups (P = .51). All patients experienced an adverse event, most of which were headache, fatigue, nausea or diarrhea. Only three patients experienced a serious adverse event, all of which were unrelated to the medication. The first patient, with grade 4 platelets before the study began only received one dose of medication, ultimately stopped receiving the study medication and was withdrawn from the study. The second patient experienced angina pectoris after completing treatment. The third patient experienced infectious colitis also after completing treatment. In addition, 22% of patients relapsed.

“Adding a third directly acting antiviral therapy to ledispasvir and sofosbuvir may result in a moderate rate of SVR, but lower than that observed in patients without cirrhosis,” Kattakuzhy and colleagues wrote. “Significant liver fibrosis remains an impediment in achieving SVR with short-duration DAA therapy.” – by Will Offit

Disclosures: Anuoluwapo Osinusi and Hongmei Mo report that they are employees of Gilead Sciences Inc. Please see the study for full list of all other authors’ relevant financial disclosures.