Paracetamol in therapeutic dosages and acute liver injury: causality assessment in a prospective case series

Background: 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. The aim is to describe the characteristics of patients admitted to hospital with jaundice who had previous exposure to therapeutic doses of paracetamol. An assessment of the causality role of paracetamol was performed in each case. Methods: Based on the evaluation of prospectively gathered cases of ALI with detailed clinical information, thirty-two cases of ALI in non-alcoholic patients exposed to therapeutic doses of paracetamol were identified. Two authors assessed all drug exposures by using the CIOMS/RUCAM scale. Each case was classified into one of five categories based on the causality score for paracetamol. Results: 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: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

Starch fermentation by faecal bacteria of infants, toddlers and adults: importance for energy salvage

Objective: Little is known of the degree to which the colon salvages energy through starch fermentation in young children. Using a simulated colonic environment, we aimed to account for the fate of fermented raw and cooked starch in two groups of young children and in adults. Design: A slurry was prepared from faecal samples from six infants ( 7 - 10 months), six toddlers ( 16 - 21 months) and seven adults ( 24 - 56 y). Each slurry was anaerobically incubated with raw or cooked maize starch in MacCartney bottles in a shaking water bath. Parallel incubations were stopped at 4 and 24 h. The headspace gas volume was analysed for CO2 and methane. The culture supernatant was analysed for short-chain fatty acids (SCFA), lactate and residual starch. Results: Different patterns of fermentation were seen at 4 and 24 h. For raw starch, the production of SCFA decreased with subject age at 4 h but not at 24 h. With both substrates at 4 h, toddler stools produced significantly more CO2 than infants or adults, but there were no statistical differences at 24 h. Methane was detected in three adults only. Lactate was detected mainly at 4 h in children. Conclusions: The results suggest that fermentation, particularly of raw starch, is a more rapid process in young children than in adults. A highly efficient energy salvage process may occur in the colon of young children