{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T22:12:27Z","timestamp":1761862347011,"version":"3.37.3"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":4140,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"name":"Roche Pharmaceuticals, Basel, Switzerland"},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"crossref","award":["32-66377.01","32-66378.01"],"award-info":[{"award-number":["32-66377.01","32-66378.01"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,5]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Hemolysis is a frequent adverse effect of ribavirin (RBV). It has been suggested that oxidative stress plays a role, but mechanisms and predictive risk factors for severe forms remain unknown. Markers of redox status were determined in erythrocytes of 34 patients with hepatitis C\u2014four of them with glucose-6-phosphate-dehydrogenase (G6PD) deficiency\u2014before and during treatment with RBV and interferon (IFN) and were compared with 10 healthy control subjects. In addition, erythrocytes were incubated with RBV, and the effects of dipyridamole (DPD), diethylmaleate (DEM), and glutathione ester (GSHE) were studied <jats:italic toggle=\"yes\">in vitro<\/jats:italic>. Of the 30 patients without G6PD deficiency who were treated with RBV and IFN-\u03b1, five developed major hemolysis (\u0394 hemoglobin &gt; 6 g\/dL) and 25 developed minor hemolysis (\u0394 hemoglobin &lt; 2.5 g\/dL). Patients with major hemolysis had lower median pretreatment values of membrane protein sulfhydrils than patients with minor hemolysis (28.4 vs. 36.7 nmol\/mg, <jats:italic toggle=\"yes\">P<\/jats:italic> &lt; .001). Erythrocytes of G6PD-deficient patients were not more susceptible to RBV-induced hemolysis. In <jats:italic toggle=\"yes\">in vitro<\/jats:italic> incubations of erythrocytes, DEM enhanced the RBV-induced decrease of glutathione, protein sulfhydrils, and osmotic resistance. Supplementation of GSHE and DPD prevented the RBV-induced decrease in osmotic resistance, adenosyl triphosphate (ATP), and 2,3-diphosphoglycerate (DPG), the loss of glutathione and protein sulfhydrils, and the formation of thiobarbituric acid reactive substances (TBARs). In conclusion, the data indicate that low membrane protein sulfhydrils prior to therapy but not G6PD deficiency are predictive of RBV-induced major hemolysis. <jats:italic toggle=\"yes\">In vitro<\/jats:italic>, GSHE and DPD reduce the RBV-associated oxidative stress in erythrocytes and prevent the increase in osmotic fragility, suggesting that these compounds might decrease the risk of hemolysis in patients. (Hepatology 2004;39:1248-1255.)<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.20208","type":"journal-article","created":{"date-parts":[[2004,4,26]],"date-time":"2004-04-26T23:01:52Z","timestamp":1083020512000},"page":"1248-1255","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":27,"title":["Low membrane protein sulfhydrils but not G6PD deficiency predict ribavirin-induced hemolysis in hepatitis C"],"prefix":"10.1097","volume":"39","author":[{"given":"Ignazio","family":"Grattagliano","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Russmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo O.","family":"Palmieri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"J\u00fcni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian","family":"Bihl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piero","family":"Portincasa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Palasciano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernhard H.","family":"Lauterburg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"R1-11-20241201","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1016\/S0140-6736(98)07124-4","article-title":"Randomised trial of interferon alpha2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. 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