Secular trends in cryoglobulinemia mortality in the USA in the era of direct-acting antivirals

BACKGROUND: Hepatitis C virus (HCV) is the main etiology of cryoglobulinemia with mortality around 25%. Little is known on the changes in cryoglobulinemia mortality after the introduction of direct-acting antivirals (DAA) for treatment of HCV in 2014 in the USA. METHODS: We used the multiple-cause mortality files compiled by the National Center for Health Statistics to calculate cryoglobulinemia mortality from 1999 to 2018. The proportionate mortality ratio (PMR) of cryoglobulinemia cases with HCV and those with autoimmune diseases was computed to assess the impact of introduction of DAA. RESULTS: We identified 1299 people aged ≥ 20 years who died with cryoglobulinemia between 1999 and 2018. The cryoglobulinemia mortality (deaths per million) declined from 1999 (0.4) to 2010 (0.22) and mildly increased to 2014 (0.26), and then decreased abruptly from 2014 to 2018 (0.19) with annual percent change of − 14.3%. The proportion of cryoglobulinemia patients with HCV was 39% (118/302) in 2009–2013 and 26% (81/310) in 2014–2018, with a PMR of 0.67 (95% CI 0.50–0.89). By contrast, the proportion of cryoglobulinemia patients with systemic autoimmune diseases was 2.6% (8/302) in 2009–2013 and 4.2% (13/310) in 2014–2018, with a PMR of 1.58 (95% CI 0.66–3.82). CONCLUSION: The changes in cryoglobulinemia mortality during the past two decades are mainly related to the aging and dying of the “baby boomer” cohort who had a high HCV prevalence and to the introduction of a DAA in 2014.