DNA Damage and Repair in Patients with Cryoglobulinemic Vasculitis Treated with Direct Anti-HCV Drugs

Mohamed Tharwat Hegazy¹, Walaa Allam², Mohamed A Hussein¹, Naguib Zoheir³, Luca Quartuccio⁴, Patrice Cacoub⁵, Wahid Doss⁶, Mona I. Ellawindi⁷, Mary Fawzy¹, Loïc Guillevin⁸, Ahmed El Ray⁹, Maissa El Said El Raziky^10,11, Magdy El Serafy⁶, Sherif El Khamisy^2,12 and Gaafar Ragab¹, ¹Internal Medicine Department, Rheumatology and Clinical Immunology Unit, Faculty of Medicine, Cairo University, Cairo, Egypt, Cairo, Egypt, ²Center for Genomics, Zewail City of Science and Technology, Giza, Egypt, Giza, Egypt, ³Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt, Cairo, Egypt, ⁴Rheumatology Clinic, Academic Hospital S. M. della Misericordia, Medical Area Department, University of Udine, Italy, Udine, Italy, ⁵Internal Medicine Department, University Hospital “Pitié-Salpêtrière”, “Pierre et Marie Curie Paris VI” University, Paris, France, Paris, France, ⁶Tropical Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt, Cairo, Egypt, ⁷Community Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt, Cairo, Egypt, ⁸Department of Internal Medicine, Referral Center for Rare Autoimmune and Systemic Diseases, Hôpital Cochin, AP–HP, Université Paris Descartes, Paris, France, Paris, France, ⁹Theodor Bilharz Research Institute, Cairo, Egypt, Cairo, Egypt, ¹⁰Fatimid Cairo hospital, Cairo, Egypt, Cairo, Egypt, ¹¹Tropical Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt, cairo, Egypt, ¹²Krebs Institute, University of Sheffield, Sheffield, S10 2TN, UK, Sheffield, United Kingdom

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Cryoglobulinemia, DNA, genomics and treatment, Hepatitis C

Session Information

Date: Sunday, October 21, 2018

Title: Vasculitis Poster I: Non-ANCA-Associated and Related Disorders

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

DNA Damage and Repair in Patients with Cryoglobulinemic Vasculitis Treated with Direct Anti-HCV Drugs Background/Purpose: Direct Acting Antiviral (DAA) agents were shown to be effective for treatment of HCV induced Cryoglobulinemic Vasculitis (HCV/CV+). Some reports showed failure of DAAs to reduce Hepatocellular carcinoma (HCC) development in HCV patients or the high risk of HCC. Although HCV replication results in hepatic stress which is associated with DNA damage, the impact of DAA on the host response to DNA damage is unknown. Our aim was to assess DNA damage and repair in CV patients treated with DAAs. Methods: This study included 32 Egyptian patients with HCV/CV+ diagnosed according to the validated 2014 classification criteria of CV. We applied 3 DAA protocols: Sofosbuvir (SOF) plus Ribavirin (RBV) plus pegylated interferon (p-IFN) for 3 months (8 patients), SOF plus RBV for 6 months (13 patients) or SOF plus Daclatasvir for 3 months (11 patients). We measured DNA damage levels in peripheral blood cells as well as DNA repair genes (TOP1, TOP2A, TDP1, TDP2, XRCC1 and PARP1) in 3 groups: healthy individuals (n=9), HCV patients without CV (HCV/CV-) (n=13) and in HCV/CV+ patients: before and at end of treatment (EOT) (n=32), at 6 months; 3 months follow up from EOT (n=19) and at 12 months follow up (n=23). Data is reported as mean ± SEM. *= p<0.05, **=p<0.005. Results: All patients showed viral clearance without recurrence, in all 3 protocols. All Patients improved clinically and serologically at EOT. After 12 months, only articular and constitutional manifestations as well as cryocrit % showed significant relapse (P value 0.009, 0.006, 0.002 respectively). HCV/CV+ patients showed increasing levels of double-strand breaks (DSBs) at EOT (p<0.05) and at 6 months point (p<0.05). However, at 12 months point, DSBs returned to pretreatment levels (Figure 1).

Figure 1: DNA damage levels: Healthy individuals (n=9), HCV-CV patients (n=13), HCV+CV at pretreatment (n=32), EOT (end of treatment) (n=32), 6 months (n=19) and 12 months (n=23).

We found no studies investigating DNA repair genes during HCV infection. We report reduced expression of all tested DNA repair genes in HCV/CV+ patients compared to patients with HCV/CV- (Figure 2).

Figure 2: Repair genes expression levels: HCV-CV patients (n=13), HCV+CV at pretreatment (n=32), EOT (end of treatment) (n=32), 6 months (n=19) and 12 months (n=23).

Conclusion:

The reported elevated levels of chromosomal breaks and the reduced expression of all tested DNA repair genes with DAAs in treating HCV/CV+ instigate deeper and more extended studies to understand the nature of our findings and evaluate the safety of these drugs.

Disclosure: M. T. Hegazy, None; W. Allam, None; M. A. Hussein, None; N. Zoheir, None; L. Quartuccio, None; P. Cacoub, Abbvie, Astra Zeneca, Bristol-Myers Squibb, Gilead, Glaxo Smith Kline, Janssen, Merck Sharp Dohme, Roche, Servier and Vifor, 5; W. Doss, None; M. I. Ellawindi, None; M. Fawzy, None; L. Guillevin, None; A. El Ray, None; M. E. S. El Raziky, None; M. El Serafy, None; S. El Khamisy, None; G. Ragab, None.

To cite this abstract in AMA style:

Hegazy MT, Allam W, Hussein MA, Zoheir N, Quartuccio L, Cacoub P, Doss W, Ellawindi MI, Fawzy M, Guillevin L, El Ray A, El Raziky MES, El Serafy M, El Khamisy S, Ragab G. DNA Damage and Repair in Patients with Cryoglobulinemic Vasculitis Treated with Direct Anti-HCV Drugs [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/dna-damage-and-repair-in-patients-with-cryoglobulinemic-vasculitis-treated-with-direct-anti-hcv-drugs/. Accessed .

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