{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T16:08:39Z","timestamp":1781712519060,"version":"3.54.5"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,7,5]],"date-time":"2006-07-05T00:00:00Z","timestamp":1152057600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2007,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Background:\u2002<\/jats:bold> The arginine\u2010degrading enzyme, arginine deiminase conjugated to polyethylene glycol (ADI\u2010SS PEG 20\u2003000\u2003mw), reduces extracellular arginine, has minimal toxicity, decreases tumor burden and improves liver function in patients with chronic hepatitis C virus infection (HCV) and inoperable hepatocellular carcinoma (HCC). Reduced extracellular arginine inhibits viral replication through unknown mechanisms. It is hypothesized that ADI\u2010SS PEG 20\u2003000\u2003mw reduces HCV viral titers through nitric oxide (NO)\u2010dependent effects.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> The effects of ADI\u2010SS PEG 20\u2003000\u2003mw (dose, 160\u2003IU\/m<jats:sup>2<\/jats:sup>; three cycles of four once\u2010weekly i.m. injections) on HCV titers, serum NO and plasma arginine, were evaluated using archived plasma from patients with HCC and HCV and <jats:italic>in vitro<\/jats:italic> cell model measurements of HCV replication.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> ADI\u2010SS PEG 20\u2003000\u2003mw selectively inhibited HCV replication <jats:italic>in vitro<\/jats:italic> (IC<jats:sub>50<\/jats:sub>\u2003=\u20030.027\u2003IU\/mL). Fifteen HCC\/HCV patients completed treatment. The HCV titers were reduced by up to 99% in five out of 10 (50%) HCV\u2010serotype 1b patients (<jats:italic>P<\/jats:italic>\u2003= 0.0093). These patients also experienced significant improvements in liver function (<jats:italic>P<\/jats:italic>\u2003= 0.0091). There were concomitant reductions of plasma arginine and serum NO levels. The HCV titer was not reduced in HCV\u2010type 2c patients.<\/jats:p><jats:p><jats:bold>Conclusion:\u2002<\/jats:bold> Reduction of extracellular arginine by ADI\u2010SS PEG 20\u2003000\u2003mw in HCC patients reduces HCV viral titers and improves liver function, possibly through suppression of NO.<\/jats:p>","DOI":"10.1111\/j.1440-1746.2006.04463.x","type":"journal-article","created":{"date-parts":[[2006,7,7]],"date-time":"2006-07-07T05:52:21Z","timestamp":1152251541000},"page":"86-91","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Pegylated arginine deiminase lowers hepatitis C viral titers and inhibits nitric oxide synthesis"],"prefix":"10.1111","volume":"22","author":[{"given":"Francesco","family":"Izzo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Montella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio Pio","family":"Orlando","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guglielmo","family":"Nasti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerardo","family":"Beneduce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Castello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Cremona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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