Direct-acting antivirals effective for HCV-related mixed cryoglobulinemia

Last Updated: 2017-03-27

By Will Boggs MD

NEW YORK (Reuters Health) - Direct-acting antivirals (DAAs) are safe and effective in some cases of mixed cryoglobulinemia related to hepatitis C virus (HCV) infection, according to two new studies.

As many as 30% of HCV-infected individuals have mixed cryoglobulinemia, which can range from being asymptomatic to causing life-threatening vasculitis. Treatment with interferon and ribavirin reduces mortality, but little is known about the effects of DAAs on HCV-related cryoglobulinemia.

In the first study, online March 14 in The American Journal of Gastroenterology, Dr. Jordan J. Feld and colleagues from the University of Toronto, Canada, describe the safety and clinical, virological and immunological efficacy of treating HCV-related mixed cryoglobulinemia (MC) and mixed cryoglobulinemic vasculitis (MCV).

Their retrospective study included 83 patients with HCV and MC who underwent antiviral therapy with one of seven regimens and 582 patients with HCV without evidence of MC.

Virological response rates were high for interferon-free regimens (92.4%) and interferon-based regimens (82.4%); 90.4% of patients with HCV and MC had sustained responses at 12 weeks (SVR12).

Complete immunological responses were observed in 50% of MC patients achieving SVR12.

Among the 18 MC patients who were symptomatic at baseline, six had complete clinical responses, two had partial responses and 10 had no response at the end of treatment. At SVR12 or SVR24, seven had complete clinical responses, four had partial responses and seven had no response.

Complete clinical response was closely tied to achievement of SVR12 and to immunological outcomes.

“The current study shows that DAA are highly effective in achieving SVR and can have significant impacts on immunological and clinical outcomes in patients with MC,” the researchers conclude. “However, robust virological responses do not guarantee rapid clinical responses. Such observations highlight that HCV-MCV is primarily an immunological disease with potential for independent immune dysregulation even after SVR.”

Dr. Robert G. Gish, a hepatologist at Stanford University, in California, who was not involved in the study, told Reuters Health by email, "This is an excellent publication that is showing data that support what we know from clinical practice: when you clear hepatitis C, you decrease the generation of antibodies that are binding hepatitis C virus and resulting immune complexes that then result in severe organ injury. This will help take this practice to first line and hopefully support providers to test for cryoglobulinemia with the rheumatoid factor in all patients.”

In the second study, online March 10 in Gastroenterology, Dr. David Saadoun from Sorbonne Universites in Paris and colleagues analyzed the efficacy and safety of 12 weeks of daily sofosbuvir and daclatasvir for HCV-associated cryoglobulinemia vasculitis in an open-label study of 41 patients with active disease.

All patients achieved SVR at week 12. At week 24, 37 patients (90.2%) were complete clinical responders and 4 (9.8%) were partial responders.

Cryoglobulinemia resolved in 50% of patients, and regulatory T-cell deficiency, memory B cell expansion, and T follicular helper cell and Th17 cell expansion reverted significantly after DAA therapy.

Seven patients experienced at least one side effect, including fatigue, nausea, vertigo, and insomnia. There were no serious adverse events.

Dr. Saadoun told Reuters Health by email, “These antiviral therapies shorten the duration of treatment of HCV-associated vasculitis . . . without the use of steroids and/or immunosuppressants. The DAA regimen sofosbuvir-daclatasvir is safe and can restore immune homeostasis in HCV-associated vasculitis patients.”

Five of the nine authors of the first study, including Dr. Feld, had various relationships with DAA manufacturers. Bristol-Myers Squibb sponsored the second study and had various relationships with six of the 13 authors, including Dr. Saadoun.

Dr. Feld did not respond to a request for comments.

SOURCE: http://bit.ly/2o9dsD3

Am J Gastroenterol 2017.

http://bit.ly/2nXl9im

Gastroenterology 2017.