Hepatic adverse drug reactions: a case/non-case study in Italy.
OBJECTIVE
Adverse drug reactions (ADRs) can involve all tissues and organs. Liver injuries are considered among the most serious and are a cause for concern among physicians and patients. To assess the extent of drug-induced liver injuries in Italy we compared the number of cases of hepatic ADRs with reports of all other drug-related reactions present in the same database.


METHODS
Spontaneous reports from six Italian Regions collected from January 1990 to May 2005 were analysed. Adverse reactions were classified according to WHO Adverse Reaction Terminology for causality assessment, and only those with "certain", "probable" or "possible" causality assessment were included. Association between drugs and hepatic ADRs was assessed using the case/non case method, calculating the ADR reporting odds ratio (ROR) as a measure of disproportionality.


RESULTS
On May 2005, the database contained 35,767 ADR reports, of which 11,829 were excluded because they were unclassifiable or unlikely in terms of causality assessment. Therefore, the analysis was carried out on 23,938 reports, of which 1,069 concerned hepatic ADRs (cases) and 22,869 concerned non-cases. The proportion of serious ADRs was about 40% in the overall database, and about 74% among cases. The drug classes with the highest number of cases were statins (ROR = 2.9, 95% CI 2.4-3.5), antiplatelet agents (ROR = 3.5; 95% CI 2.6-4.6), NSAIDs (ROR = 2.9; 95% CI 2.1-3.9) and macrolides (ROR = 1.7; 95% CI 1.2-2.3).


CONCLUSIONS
Hepatic adverse drug reactions remain a serious concern for several drugs widely used in clinical practice. Monitoring hepatic enzymes on a monthly basis for the first 6 months of treatment has been suggested for patients taking medications known to be hepatotoxic. A better knowledge of the epidemiology and mechanisms of hepatic ADRs may contribute to minimising their occurrence.
Motola
Domenico
D
Department of Pharmacology and Interuniversity Research Centre for Pharmacoepidemiology, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy.
Vargiu
Antonio
A
Leone
Roberto
R
Cocci
Alfredo
A
Salvo
Francesco
F
Ros
Barbara
B
Meneghelli
Ilaria
I
Venegoni
Mauro
M
Cutroneo
Paola Maria
PM
Vaccheri
Alberto
A
Velo
Gianpaolo
G
Montanaro
Nicola
N
D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data*; D000900:Anti-Bacterial Agents / Q000009:adverse effects; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D056486:Chemical and Drug Induced Liver Injury; D016208:Databases, Factual; D016903:Drug Monitoring; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects; D007049:Iatrogenic Disease / Q000453:epidemiology; D007558:Italy / Q000453:epidemiology; D018942:Macrolides / Q000009:adverse effects; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects
D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018942:Macrolides; D010975:Platelet Aggregation Inhibitors