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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 &amp; Sj\u00f6gren\u2019s disease (SjD).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We studied 60 patients in 3 groups: Group 1 (20 HCV\u2009+\u2009sicca), 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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>All HCV cases had sustained viral response (SVR). Comparing the characteristics of groups 1 (before treatment) &amp; 3: Group 1 had a higher frequency of RF, cryoglobulins, and polyclonal-hypergammaglobulinemia (<jats:italic>P<\/jats:italic>-values 0.021, 0.003, and \u02c20.001 respectively). Group 3 had higher scores of VAS dry eye, VAS dry mouth, VAS fatigue, and VAS pain than group 1 (<jats:italic>P<\/jats:italic>-values \u02c20.001 in all). Group 3 also had a higher frequency of Anti-Ro and Anti-La (<jats:italic>P<\/jats:italic>-values\u2009&lt;\u20090.001). Group-1 before DAAs treatment had higher markers denoting B-cell hyperactivity [higher Rheumatoid factor (RF), cryoglobulins, and beta2-microglobulins (\u03b22M)] 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 (<jats:italic>P<\/jats:italic>-values \u02c20.003, \u02c20.002, \u02c20.016, \u02c20.001, \u02c20.002, and \u02c20.014 respectively). There was a significant improvement in RF, and serum \u03b22M levels (after SVR), (<jats:italic>P<\/jats:italic>-values \u02c20.013, and 0.001 respectively). Group 1 is further ahead in the direction of lymphoproliferation than group 2 with higher statistically significant serum \u03b22M and polyclonal serum protein electrophoresis (<jats:italic>P<\/jats:italic>-values 0.006 and 0.047 respectively).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13075-025-03605-9","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T08:06:20Z","timestamp":1751875580000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Sicca manifestations and lymphoproliferation in hepatitis C virus: effects of direct acting antiviral therapy on dryness and B-cell activity compared to Sj\u00f6gren\u2019s disease"],"prefix":"10.1186","volume":"27","author":[{"given":"Amina","family":"Maher","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed Tharwat","family":"Hegazy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tareq M.","family":"Algarf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manar A.","family":"Abdul-Aziz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Quartuccio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naguib","family":"Zoheir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"De Vita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6529-0334","authenticated-orcid":false,"given":"Gaafar","family":"Ragab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,7]]},"reference":[{"key":"3605_CR1","doi-asserted-by":"publisher","unstructured":"Cacoub P, Buggisch P, Carri\u00f3n JA, Cooke GS, Zignego AL, Beckerman R et al. 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A written informed consent was obtained from all participating patients.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"139"}}