Background: Hepatitis C virus (HCV) is often associated with autoimmune features and extra-hepatic manifestations. Sicca symptoms are reported in about 30% of the cases. Both HCV and Sjögren’s disease (SjD) are associated with hyperactivation of B-cells and lymphocytic infiltration of salivary and lacrimal glands. About half of HCV-infected patients have focal sialadenitis simulating SjD.

Objectives: To study the effect of the direct-acting antivirals (DAAs) on sicca manifestations in HCV-patients and to study the difference between those patients and those with SjD.

Methods: This study included 60 patients divided into 3 groups: Group 1 included 20 patients with active HCV and sicca manifestations, Group 2 included 20 patients with HCV without sicca manifestations and Group 3 included 20 patients with SjD. Groups 1 and 2 received treatment with DAAs and were assessed clinically and serologically before and 6 months after finishing treatment. Group 3 was evaluated the same once.

Results: After DAAs, all HCV cases had sustained viral response (SVR). Comparing the characteristics of groups 1& 3: Group 1 patients had a statistically higher frequency of rheumatoid factor (RF) (50% vs. 25%), serum cryoglobulins (40% vs. 0%) and polyclonal hypergammaglobulinemia (60% vs. 25%) with p values 0.021, 0.003 and 0.00 respectively compared to group 3. While group 3 patients had higher statistically significant VAS dry eye score, VAS dry mouth score, VAS fatigue, and VAS pain figures (P values 0.000 in all) compared to group 1. Also, group 3 patients had a higher frequency of Anti-Ro (80% vs. 0%) and Anti-La (65% vs. 5%) antibodies (P values <0.001 in both) compared to group 1.

Group 1 patients after SVR showed marked statistical improvement in VAS dry eye, VAS dry mouth, VAS fatigue, VAS pain, ESSPRI, and ESSDAI after treatment (P values <0.003, <0.002, <0.016, 0.000, <0.002 and <0.014 respectively). Immunologically there was a statistically significant improvement in RF, and serum Beta 2 microglobulins (β2M) (P values <0.013 and 0.001 respectively). Serum Cryoglobulins were negative in all patients after antiviral treatment (40% pre vs. 0% post).

Group 2 patients after SVR showed improvement in serum cryoglobulins after DAAs treatment (15% vs. 0% post). There was no statistically significant improvement in RF (25% vs. 20% post) and IgG (25% vs. 25%) (P values <0.293 and <0.794, respectively).

Group 1 patients before DAAs had higher markers denoting hyperactive B-cells (higher RF, cryoglobulins, and β2M) compared to group 2 that improved markedly after SVR. Group 1 showed significant improvement of sicca symptoms and immunological profile after clearance of HCV as well as significant improvement of β2M.

Conclusion: Treatment of cases with HCV and sicca manifestations by DAAs is associated with significant clinical and immunological improvement. HCV with sicca manifestations showed higher markers denoting B-cell hyperactivity that improved markedly after HCV clearance. So we recommend longer follow-up for these patients and their prioritization for early treatment. This could halt or delay the risk of lymphoproliferation.

The difference between group 1 (before and after SVR) and group 3, supports that they are 2 different diseases, with different characteristic features, as they showed improvement of Sicca symptoms after eradication of HCV. So we suggest that even treated HCV infection should be excluded from the classification criteria for the diagnosis of Primary Sjögren disease (which excluded only active HCV in the current form).

REFERENCES: [1] Cacoub P, Buggisch P, Carrión JA, Cooke GS, Zignego AL, Beckerman R et al. Direct medical costs associated with the extrahepatic manifestations of hepatitis C infection in Europe. J Viral Hepat. 2018; 25(7):811-7.

[2] Alves M, Angerami RN, Rocha EM. Dry eye disease caused by viral infection: [review]. Arq Bras Oftalmol. 2013 Mar-Apr; 76(2):129-32

[3] Loustaud-Ratti V, Riche A, Liozon E, Labrousse F, Soria P, Rogez S et al. Prevalence and characteristics of Sjögren’s syndrome or Sicca syndrome in chronic hepatitis C virus infection: a prospective study. J Rheumatol. 2001;28(10):2245-51.

Acknowledgements: NIL.

Disclosure of Interests: None declared.