@article{de_abajo_acute_2004,
	title = {Acute and clinically relevant drug-induced liver injury: a population based case-control study},
	volume = {58},
	issn = {0306-5251},
	shorttitle = {Acute and clinically relevant drug-induced liver injury},
	doi = {10.1111/j.1365-2125.2004.02133.x},
	abstract = {AIMS: To provide quantitative information about the absolute and relative risks of acute and clinically relevant drug-induced liver injury.
METHODS: We performed a population-based case-control study using the UK-based General Practice Research Database as the source of information. A total of 1,636,792 persons subjects aged 5-75 years old registered in the database from 1 January, 1994 to 31 December, 1999 were followed-up for a total of 5,404,705 person-years. 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-time of study cohort. Current users were defined if a prescription ended within 15 days of the index date, and nonusers if there was no prescription before the index date.
RESULTS: One hundred and twenty-eight patients were considered as valid cases, being the crude incidence rate of 2.4 (95\% confidence interval: 2.0, 2.8) per 100 000 person-years. The strongest associations were found with chlorpromazine (adjusted odds ratio (AOR); 95\% CI = 416; 45, 3840), amoxicillin/clavulanic acid (AOR = 94.8; 27.8, 323), flucloxacillin (AOR = 17.7; 4.4, 71.0), macrolides (AOR = 6.9; 2.3, 21.0), tetracyclines (AOR = 6.2; 2.4, 15.8); metoclopramide (AOR = 6.2; 1.8, 21.3); chlorpheniramine (AOR = 9.6; 1.9, 49.7); betahistine (AOR = 15.3; 2.9, 80.7); sulphasalazine (AOR = 25.5; 6.0, 109); azathioprine (AOR = 10.5; 1.4, 76.4), diclofenac (AOR = 4.1; 1.9, 8.8) and antiepileptics (AOR = 5.1; 1.9, 13.7). A dose-effect 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).
CONCLUSIONS: 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.},
	language = {eng},
	number = {1},
	journal = {British Journal of Clinical Pharmacology},
	author = {de Abajo, Francisco J. and Montero, Dolores and Madurga, Mariano and García Rodríguez, Luis A.},
	month = jul,
	year = {2004},
	pmid = {15206996},
	pmcid = {PMC1884531},
	keywords = {Acute Disease, Adolescent, Adult, Age Factors, Aged, Case-Control Studies, Child, Child, Preschool, Drug-Induced Liver Injury, Female, Humans, Male, Middle Aged, Risk Factors},
	pages = {71--80}
}

{"_id":"8RTpBTJYxxtnuuCSd","bibbaseid":"deabajo-montero-madurga-garcarodrguez-acuteandclinicallyrelevantdruginducedliverinjuryapopulationbasedcasecontrolstudy-2004","downloads":0,"creationDate":"2017-08-15T09:38:11.036Z","title":"Acute and clinically relevant drug-induced liver injury: a population based case-control study","author_short":["de Abajo, F. J.","Montero, D.","Madurga, M.","García Rodríguez, L. A."],"year":2004,"bibtype":"article","biburl":"http://bibbase.org/zotero/veegee78","bibdata":{"bibtype":"article","type":"article","title":"Acute and clinically relevant drug-induced liver injury: a population based case-control study","volume":"58","issn":"0306-5251","shorttitle":"Acute and clinically relevant drug-induced liver injury","doi":"10.1111/j.1365-2125.2004.02133.x","abstract":"AIMS: To provide quantitative information about the absolute and relative risks of acute and clinically relevant drug-induced liver injury. METHODS: We performed a population-based case-control study using the UK-based General Practice Research Database as the source of information. A total of 1,636,792 persons subjects aged 5-75 years old registered in the database from 1 January, 1994 to 31 December, 1999 were followed-up for a total of 5,404,705 person-years. 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-time of study cohort. Current users were defined if a prescription ended within 15 days of the index date, and nonusers if there was no prescription before the index date. RESULTS: One hundred and twenty-eight patients were considered as valid cases, being the crude incidence rate of 2.4 (95% confidence interval: 2.0, 2.8) per 100 000 person-years. The strongest associations were found with chlorpromazine (adjusted odds ratio (AOR); 95% CI = 416; 45, 3840), amoxicillin/clavulanic acid (AOR = 94.8; 27.8, 323), flucloxacillin (AOR = 17.7; 4.4, 71.0), macrolides (AOR = 6.9; 2.3, 21.0), tetracyclines (AOR = 6.2; 2.4, 15.8); metoclopramide (AOR = 6.2; 1.8, 21.3); chlorpheniramine (AOR = 9.6; 1.9, 49.7); betahistine (AOR = 15.3; 2.9, 80.7); sulphasalazine (AOR = 25.5; 6.0, 109); azathioprine (AOR = 10.5; 1.4, 76.4), diclofenac (AOR = 4.1; 1.9, 8.8) and antiepileptics (AOR = 5.1; 1.9, 13.7). A dose-effect 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). CONCLUSIONS: 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.","language":"eng","number":"1","journal":"British Journal of Clinical Pharmacology","author":[{"propositions":["de"],"lastnames":["Abajo"],"firstnames":["Francisco","J."],"suffixes":[]},{"propositions":[],"lastnames":["Montero"],"firstnames":["Dolores"],"suffixes":[]},{"propositions":[],"lastnames":["Madurga"],"firstnames":["Mariano"],"suffixes":[]},{"propositions":[],"lastnames":["García","Rodríguez"],"firstnames":["Luis","A."],"suffixes":[]}],"month":"July","year":"2004","pmid":"15206996","pmcid":"PMC1884531","keywords":"Acute Disease, Adolescent, Adult, Age Factors, Aged, Case-Control Studies, Child, Child, Preschool, Drug-Induced Liver Injury, Female, Humans, Male, Middle Aged, Risk Factors","pages":"71--80","bibtex":"@article{de_abajo_acute_2004,\n\ttitle = {Acute and clinically relevant drug-induced liver injury: a population based case-control study},\n\tvolume = {58},\n\tissn = {0306-5251},\n\tshorttitle = {Acute and clinically relevant drug-induced liver injury},\n\tdoi = {10.1111/j.1365-2125.2004.02133.x},\n\tabstract = {AIMS: To provide quantitative information about the absolute and relative risks of acute and clinically relevant drug-induced liver injury.\nMETHODS: We performed a population-based case-control study using the UK-based General Practice Research Database as the source of information. A total of 1,636,792 persons subjects aged 5-75 years old registered in the database from 1 January, 1994 to 31 December, 1999 were followed-up for a total of 5,404,705 person-years. 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-time of study cohort. Current users were defined if a prescription ended within 15 days of the index date, and nonusers if there was no prescription before the index date.\nRESULTS: One hundred and twenty-eight patients were considered as valid cases, being the crude incidence rate of 2.4 (95\\% confidence interval: 2.0, 2.8) per 100 000 person-years. The strongest associations were found with chlorpromazine (adjusted odds ratio (AOR); 95\\% CI = 416; 45, 3840), amoxicillin/clavulanic acid (AOR = 94.8; 27.8, 323), flucloxacillin (AOR = 17.7; 4.4, 71.0), macrolides (AOR = 6.9; 2.3, 21.0), tetracyclines (AOR = 6.2; 2.4, 15.8); metoclopramide (AOR = 6.2; 1.8, 21.3); chlorpheniramine (AOR = 9.6; 1.9, 49.7); betahistine (AOR = 15.3; 2.9, 80.7); sulphasalazine (AOR = 25.5; 6.0, 109); azathioprine (AOR = 10.5; 1.4, 76.4), diclofenac (AOR = 4.1; 1.9, 8.8) and antiepileptics (AOR = 5.1; 1.9, 13.7). A dose-effect 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).\nCONCLUSIONS: 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.},\n\tlanguage = {eng},\n\tnumber = {1},\n\tjournal = {British Journal of Clinical Pharmacology},\n\tauthor = {de Abajo, Francisco J. and Montero, Dolores and Madurga, Mariano and García Rodríguez, Luis A.},\n\tmonth = jul,\n\tyear = {2004},\n\tpmid = {15206996},\n\tpmcid = {PMC1884531},\n\tkeywords = {Acute Disease, Adolescent, Adult, Age Factors, Aged, Case-Control Studies, Child, Child, Preschool, Drug-Induced Liver Injury, Female, Humans, Male, Middle Aged, Risk Factors},\n\tpages = {71--80}\n}\n\n","author_short":["de Abajo, F. 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