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Comparative Study
. 2025 Jul 7;27(1):139.
doi: 10.1186/s13075-025-03605-9.

Sicca manifestations and lymphoproliferation in hepatitis C virus: effects of direct acting antiviral therapy on dryness and B-cell activity compared to Sjögren's disease

Amina Maher  1 , Mohamed Tharwat Hegazy  1 , Tareq M Algarf  2 , Manar A Abdul-Aziz  3 , Luca Quartuccio  4 , Naguib Zoheir  5 , Salvatore De Vita #  4 , Gaafar Ragab #  6
Affiliations
Comparative Study

Sicca manifestations and lymphoproliferation in hepatitis C virus: effects of direct acting antiviral therapy on dryness and B-cell activity compared to Sjögren's disease

Amina Maher et al. Arthritis Res Ther. .

Abstract

Objectives: Hepatitis C virus (HCV) can be associated with sicca manifestations. To study the effect of direct-acting antivirals (DAAs) on sicca manifestations in HCV-infected patients and the difference between those patients and others with HCV without dryness & Sjögren's disease (SjD).

Methods: We studied 60 patients in 3 groups: Group 1 (20 HCV + sicca), group 2 (20 HCV without sicca), and group 3 (20 SjD). Groups 1 and 2 received DAAs according to the Egyptian Ministry of Health protocols and were evaluated before and after treatment. Group 3 was evaluated once. Our study evaluated the patients by both subjective and objective methods.

Results: All HCV cases had sustained viral response (SVR). Comparing the characteristics of groups 1 (before treatment) & 3: Group 1 had a higher frequency of RF, cryoglobulins, and polyclonal-hypergammaglobulinemia (P-values 0.021, 0.003, and ˂0.001 respectively). Group 3 had higher scores of VAS dry eye, VAS dry mouth, VAS fatigue, and VAS pain than group 1 (P-values ˂0.001 in all). Group 3 also had a higher frequency of Anti-Ro and Anti-La (P-values < 0.001). Group-1 before DAAs treatment had higher markers denoting B-cell hyperactivity [higher Rheumatoid factor (RF), cryoglobulins, and beta2-microglobulins (β2M)] compared to group-2 which improved markedly after SVR. This supports that group 1 is further ahead in the direction of lymphoproliferation. Group 1 patients after SVR showed marked improvement in VAS dry eye, VAS dry mouth, VAS fatigue, VAS pain, ESSPRI, and ESSDAI (P-values ˂0.003, ˂0.002, ˂0.016, ˂0.001, ˂0.002, and ˂0.014 respectively). There was a significant improvement in RF, and serum β2M levels (after SVR), (P-values ˂0.013, and 0.001 respectively). Group 1 is further ahead in the direction of lymphoproliferation than group 2 with higher statistically significant serum β2M and polyclonal serum protein electrophoresis (P-values 0.006 and 0.047 respectively).

Conclusion: HCV patients with sicca manifestations treated by DAAs showed significant clinical and immunological improvements. The difference between group 1 (before and after SVR) and group 3 supports the notion that they are two different entities, with different characteristic features. Sicca manifestations improved after the eradication of HCV.

Keywords: B-cell proliferation; Direct-acting antiviral drugs; Hepatitis C virus; Sicca manifestations; Sjögren’s disease.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: All procedures performed in the study were in accordance with the ethical standards of the National Research Committee and the 1964 Helsinki Declaration and its later amendments and approved by the Research Ethics Committee, Faculty of Medicine, Cairo University (REC code: D-28-19). A written informed consent was obtained from all participating patients. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Comparison between the characteristics of group 1 (before and after HCV treatment by DAAs) and group 3 OSS: Ocular staining surface, USSF: Unstimulated salivary flow, ANA: Anti-nuclear antibodies, RF: Rheumatoid factor, C3: Complement 3, β2M: beta2-microglobulin, SPEP: serum protein electrophoresis, DAAs: Direct antiviral Agents,
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