Direct-acting viral combination safely treats advanced fibrosis and compensated cirrhosis

A combination of direct-acting antiviral (DAA) agents sofosbuvir and velpatasvir is highly effective and safe for treating patients with hepatitis C virus (HCV) genotypes 1 to 6 and advanced fibrosis or compensated cirrhosis, according to a new study.

Patients with advanced fibrosis or compensated cirrhosis are a priority group for immediate HCV treatment. Historically, interferon-based regimens led to higher rates of toxicity and lower rates of sustained virologic response (SVR) in these patients, state the authors, led by Tarik Asselah, of the University Paris-Diderot, Clichy, France.

An analysis of 501 adult patients from 3 large phase 3 trials with compensated cirrhosis or advanced fibrosis who received sofosbuvir plus velpatasvir for 12 weeks found 98 percent of patients achieved SVR at 12 weeks after the end of treatment (SVR12).
“Sofosbuvir-velpatasvir is highly effective in patients infected with HCV with advanced fibrosis or cirrhosis,” said Asselah.
The researchers published their results in the March 2018 edition of Liver International.

In the retrospective pooled analysis, patients with HCV genotype 1 to 6 infection received a fixed-dose combination containing 400 mg of sofosbuvir and 100 mg of velpatasvir orally once daily for 12 weeks. About half (44 percent) of the patients had cirrhosis.

Participants included a pooled subset of patients with chronic HCV and advanced fibrosis or compensated cirrhosis from the phase III ASTRAL-1, ASTRAL-2 and ASTRAL-3 trials. ASTRAL-1 was conducted in the United States, Canada, Europe, and Hong Kong. ASTRAL-2 was conducted in the United States. ASTRAL-3 was conducted in the United States, Canada, Europe, Australia, and New Zealand.

All HCV genotypes were represented. The most common HCV genotypes were genotype 1 (34 percent) and genotype 3 (31 percent). More than one-third (38 percent) of patients were treatment-experienced, and one-third of the total had received peginterferon-based therapy.
Patients with cirrhosis had an SVR12 rate of 96 percent (212 of 220 patients), and those with advanced fibrosis had an SVR12 rate of 99 percent (278 of 281 patients). Response rates were similar among other evaluated subgroups of patients, said Asselah.

SVR12 was 98 percent (306 of 311 patients) for treatment-naïve patients and 97 percent (184 of 190 patients) for treatment-experienced patients.

Of the patients with HCV genotype 3 who had cirrhosis at baseline, 91 percent (73 of 80 patients) achieved SVR12. “These are the highest reported SVR rates for HCV genotype 3-infected patients, who have been more challenging to cure even with the newer regimens containing DAAs,” said Asselah.

No patients had virologic failure on treatment. Ten patients did not achieve SVR12. They all had virologic relapse after the end of treatment. Eight of these patients had HCV genotype 3 infection, and 2 patients had HCV genotype 1 infection. Seven of the patients who relapsed had cirrhosis.

The most common adverse events were headache, fatigue, nausea and nasopharyngitis. No patients discontinued treatment because of an adverse event.

“Sofosbuvir plus velpatasvir is a highly effective, safe pangenotypic treatment for patients with chronic HCV infection and advanced fibrosis or compensated cirrhosis, a population that was previously considered difficult to treat,” said Asselah.