{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,13]],"date-time":"2026-11-13T11:46:48Z","timestamp":1794570408987,"version":"4.9.1"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2004,4,22]],"date-time":"2004-04-22T00:00:00Z","timestamp":1082592000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2004,7]]},"abstract":"<jats:p><jats:bold>Aims\u2002<\/jats:bold>To provide quantitative information about the absolute and relative risks of acute and clinically relevant drug\u2010induced liver injury.<\/jats:p><jats:p><jats:bold>Methods\u2002<\/jats:bold>We performed a population\u2010based case\u2010control study using the UK\u2010based General Practice Research Database as the source of information. A total of 1636792 persons subjects aged 5\u201375\u2003years old registered in the database from 1 January, 1994 to 31 December, 1999 were followed\u2010up for a total of 5404705 person\u2010years. Cases were identified by an exhaustive computer search, then reviewed manually and finally validated against the clinical records. Only idiopathic cases serious enough to be referred to hospital or a consultant were selected. A total of 5000 controls were randomly sampled from the person\u2010time of study cohort. Current users were defined if a prescription ended within 15\u2003days of the index date, and nonusers if there was no prescription before the index date.<\/jats:p><jats:p><jats:bold>Results\u2002<\/jats:bold>One hundred and twenty\u2010eight patients were considered as valid cases, being the crude incidence rate of 2.4 (95% confidence interval: 2.0, 2.8) per 100\u2003000 person\u2010years. The strongest associations were found with chlorpromazine (adjusted odds ratio (AOR); 95% CI\u2003=\u2003416; 45, 3840), amoxicillin\/clavulanic acid (AOR\u2003=\u200394.8; 27.8, 323), flucloxacillin (AOR\u2003= 17.7; 4.4, 71.0), macrolides (AOR\u2003=\u20036.9; 2.3, 21.0), tetracyclines (AOR\u2003=\u20036.2; 2.4, 15.8); metoclopramide (AOR\u2003=\u20036.2; 1.8, 21.3); chlorpheniramine (AOR\u2003=\u20039.6; 1.9, 49.7); betahistine (AOR\u2003=\u200315.3; 2.9, 80.7); sulphasalazine (AOR\u2003=\u200325.5; 6.0, 109); azathioprine (AOR\u2003=\u200310.5; 1.4, 76.4), diclofenac (AOR\u2003=\u20034.1; 1.9, 8.8) and antiepileptics (AOR\u2003=\u20035.1; 1.9, 13.7). A dose\u2010effect was apparent for diclofenac, amoxicillin\/clavulanic acid and flucloxacillin. The combination of two or more hepatotoxic drugs increased the risk by a factor of 6. The highest crude incidence rates were found for chlorpromazine, azathioprine, and sulfasalazine (about 1 per 1000 users).<\/jats:p><jats:p><jats:bold>Conclusions\u2002<\/jats:bold>Idiopathic, acute and clinically relevant liver injury, which has the use of drugs as the most probable aetiology, is a rare event in the general population. The relative risks of 40 drugs\/therapeutic classes are provided, along with the crude incidence rates for 15 of them where a statistical association was found.<\/jats:p>","DOI":"10.1111\/j.1365-2125.2004.02133.x","type":"journal-article","created":{"date-parts":[[2004,6,21]],"date-time":"2004-06-21T08:09:15Z","timestamp":1087805355000},"page":"71-80","source":"Crossref","is-referenced-by-count":361,"title":["Acute and clinically relevant drug\u2010induced liver injury: a population based case\u2010control study"],"prefix":"10.1111","volume":"58","author":[{"given":"Francisco J.","family":"De Abajo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dolores","family":"Montero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariano","family":"Madurga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis A. 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