dc.description.abstract
Background: Acute serious liver disease (ASLD) of uncertain aetiology is often drug related and quantitative information about the associated risk is scarce.
Acute liver injury (ALI) induced by paracetamol overdose is a well known cause of emergency hospital admission and death. However, there is debate regarding the risk of ALI after therapeutic dosages of the drug.
We aimed to estimate the risk of ASLD associated with the use of drugs and to describe the characteristics of patients admitted to hospital with jaundice who had previous exposure to therapeutic doses of paracetamol.
Methods: In a population survey study, 126 cases of ASLD were prospectively assembled from January 1993 to December 1999, in patients over 15 years of age, in 12 hospitals in Barcelona (Spain). We estimated the relative risk (RR) for each drug as the ratio between the incidence of ASLD among the exposed population to the drug and the incidence of ASLD among those non-exposed to it. Drug consumption data were used to estimate the exposed population.
Two authors assessed all paracetamol exposures by using the CIOMS/RUCAM scale. Each case was classified into one of five categories based on the causality score for paracetamol.
Results: Isoniazid, pyrazinamide, rifampicin, amoxicillin with clavulanic acid, erythromicin, chlorpromazine, nimesulide, and ticlopidine presented the highest risk (point RR >25). Amoxicillin, metoclopramide, captopril and enalapril, furosemide, hydrochlorothiazide, fluoxetine, paroxetine, diazepam, alprazolam, lorazepam, metamizole, low-dose acetylsalicylic acid and salbutamol showed the lowest risk (point RR <5). In four cases the role of paracetamol was judged to be unrelated, in two unlikely, and these were excluded from evaluation. In seven of the remaining 26 cases, the RUCAM score associated with paracetamol was higher than that associated with other concomitant medications. The estimated incidence of ALI related to the use of paracetamol in therapeutic dosages was 0.4 per million inhabitants older than 15 years of age and per year (99%CI, 0.2-0.8) and of 10 per million paracetamol users-year (95% CI 4.3-19.4).
Conclusions: This study provides a risk estimation of serious liver disease for various drugs that will be useful in its diagnosis and management, and when comparing with the drug therapeutic benefit in each indication. Some observed associations would be worth testing in specific studies. Regarding the use of paracetamol our results indicate that paracetamol in therapeutic dosages may be considered in the causality assessment in non-alcoholic patients with liver injury, even if the estimated incidence of ALI related to paracetamol appears to be low.
eng
