• What are the Long-term Effects of DAA Therapy on HCV-associated Cryoglobulinemia Vasculitis?

What are the Long-term Effects of DAA Therapy on HCV-associated Cryoglobulinemia Vasculitis?

More than 95% of patients with hepatitis C virus–associated cryoglobulinemia vasculitis (HCV-CryoVas) have a full or partial response of symptoms to treatment with direct-acting antiviral (DAA) agents, researchers report in a long-term follow-up study in the February issue of Clinical Gastroenterology and Hepatology. Fewer than 5% of patients stopped therapy prematurely and fewer than 3% died. A severe form of CryoVas and peripheral neuropathy were associated with a lack of response of CryoVas to DAA therapy.

Complete clinical response of HCV-CryoVas to different DAAs after adjustment for severity of the vasculitis and type of mixed cryoglobulin.

CryoVas is an immune complex–mediated systemic vasculitis that affects mainly small- and medium-sized vessels—it is observed in approximately 15% of patients with HCV infection and has an estimated 5-year mortality rate of 25%. Outcomes of patients with HCV-CryoVas associate with level of liver fibrosis and vasculitis of the kidney, central nervous system, heart, and digestive tract. Remission of vasculitis is associated with reponse to DAA therapy; a complete clinical response was reported in 90.2% of patients with HCV-CryoVas.

Patrice Cacoub et al aimed to evaluate the effectiveness and tolerance of different DAA treatment combinations, and search for factors associated with complete remission of vasculitis manifestations, in 148 patients with HCV-CryoVas (median age, 57 years; 53.7% with cirrhosis; 49.3% not previously treated with DAAs). All patients received DAA agents (sofosbuvir plus daclatasvir, n = 53; sofosbuvir plus ribavirin, n = 51; sofosbuvir plus ledipasvir, n = 23; or sofosbuvir plus simeprevir, n = 18), for 12 or 24 weeks.

A complete response (improvement of all organs involved at baseline, without relapse) was observed in 106 patients (72.6%), a partial response (improvements in some organs) in 33 patients (22.6%), and no response was observed in 7 patients (4.8%). Cryoglobulins were no longer detected in blood samples from 53.1% of patients, and 97.2% of the patients had a sustained virologic response to therapy.

Factors associated with no or partial response to therapy included a severe form of CryoVas (odds ratio, 0.33) and peripheral neuropathy (odds ratio, 0.31). After a median follow-up time of 15.3 months, 4 patients (2.8%) died. The CryoVas manifestation of purpura was cleared from 97.2% of patients, renal involvement from 91.5% of patients, arthralgia from 85.7% of patients, neuropathy from 77.1% of patients, and cryoglobulinemia from 52.2%.

Premature withdrawal of DAA agents, due to side effects, was reported for 6 (4.1%) patients.

The rates of complete remission of CryoVas manifestations at week 12 after DAA treatment and at the end of the follow-up period were 62% and 70% for sofosbuvir plus ribavirin, 67% and 72% for SOF plus simeprevir, 79% and 88% for sofosbuvir plus daclatasvir, and 87% and 87% for sofosbuvir plus ledipasvir.

When Cacoub et al used sofosbuvir plus ribavirin combination as a reference group (because of the lowest response rate), only the combination of sofosbuvir plus ledipasvir showed significant superiority (odds ratio, 4.09). The authors say there was a superiority trend for the combination of sofosbuviru plus daclatasvir (odds ratio, 2.28) (see figure). The results were similar when the model was adjusted for the severity of vasculitis, type III mixed cryoglobulinemia, and B-cell lymphoma.

Fewer than 15% of patients required corticosteroids or immunosuppressants in combination with the DAA therapy. Cacoub et al write that a longer follow-up evaluation of HCV-CryoVas patients with eradication of hCV and persistent detectable cryoglobulinemia is required to evaluate the remaining risk of lymphoma.

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