Session Information
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose:
Cryoglobulinemic vasculitis (CV) is an extrahepatic manifestation of chronic HCV infection. It varies in severity from mild to life threatening. Some but not all patients with HCV infection and CV harbor B cell clonal expansions that are somatically hypermutated and show features of an antigen-driven response, with IgM+CD27+ B cell subset overrepresentation of VH1–69 and Vκ3–20 variable genes that encode RFs of the Wa cross-reactive idiotype, Re-arrangement of the bcl-2 gene via a t (14:18) translocation has also been observed.
To begin to determine mechanisms underlying B cell derangement during chronic HCV infection we assessed the variability of decline rate of rheumatoid factor (RF) levels in HCV infected patients treated with interferon free DAA therapy.
Methods:
130 Chronic HCV infected participants undergoing IFN free HCV therapy (Sofosbuvir/ledipisvir for 8 weeks or Sofosbuvir/Ledipisvir/Ribavirin for 12 weeks) were enrolled from the Cleveland VA . They had chronic HCV infection (>6 months seropositive and RNA positive) with absence of serum Hepatitis B surface antigen and HIV antibody, and they were treated with IFN free DAA HCV. Serum IgM RF and soluble CD14 (sCD14) were determined by ELISA.
After identifying 44 RF+ participants, we measured RF levels longitudinally in 44 RF+, 6 RF intermediate, and 3 RF- participants at weeks 0, 4, 8, 12 and 20-24 after initiating curative IFN free DAA HCV therapy, and clinical parameters correlating with RF decline were evaluated.
Results:
All participants achieved a sustained virologic response at week 12 after therapy cessation (SVR12), and all also achieved a SVR24. After DAA therapy initiation, all RF- and RF intermediate participants remained RF- and intermediate respectively. 100%, 73%, 80% and 69% of RF+ participants remained RF+ at weeks 0, 4, 8 and 20-24. 10% of these had no evidence of declining RF level, while RF decline rate appeared similar between those that remained RF positive and those that became RF negative at the completion of the study. Before therapy RF level was associated with albumin level after completion of therapy (r=0.417 p=0.013), and albumin level after completion of therapy was also associated with RF decline magnitude (r= 0.504, p=0.002). Additionally, baseline sCD14 was correlated with week 4 RF level (r=0.654 p=0.002), thus factors that induce Kupffer cell production of sCD14 may also participate in hepatic support for RF production.
Conclusion:
These data indicate wide variability in RF decline rate, and provide support for a model where factors other than HCV itself participate in determining RF level during chronic active HCV infection, as well as RF decline during IFN free DAA therapy. Further definition of factors contributing to persistence of RF may help guide therapeutic approaches for HCV associated cryoglobulinemic vasculitis.
To cite this abstract in AMA style:
Kowal C, Shive C, Zebrowski E, Kostadinova L, Fuller B, Reyes E, Rife K, Hirsch A, Compan A, Kottilil S, Falck-Ytter Y, Calabrese LH, Anthony D, Mattar M. Rheumatoid Factor (RF) Levels Remain Persistently Elevated 24 Weeks after Interferon (INF) Free Direct Antiviral Agents (DAA) Therapy in the Majority of RF+ HCV Infected Persons [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/rheumatoid-factor-rf-levels-remain-persistently-elevated-24-weeks-after-interferon-inf-free-direct-antiviral-agents-daa-therapy-in-the-majority-of-rf-hcv-infected-persons/. Accessed .« Back to 2017 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/rheumatoid-factor-rf-levels-remain-persistently-elevated-24-weeks-after-interferon-inf-free-direct-antiviral-agents-daa-therapy-in-the-majority-of-rf-hcv-infected-persons/