In conjunction with INR and a suitable mathematical model describing these mechanisms, however,

see more aminotransferase levels do contain sufficient information to estimate the timing and amount of overdose. Our model cannot distinguish patients with high overdose amounts and early administration of N-Ac from patients with low overdose amounts and delayed treatment because in both cases AST, ALT, and INR levels are low. However, this ambiguity affects only patients who are predicted to recover. Some patients with unique characteristics, such as those with significant muscle damage, may not fit the model. Muscle damage increases the level of AST, which may lead to poor estimation of liver damage. Because ALT and INR values are not affected by muscle damage, this effect may be minimal. Further studies are warranted to determine whether more refinements are needed for special patient groups. Our treatment

of all patients as having the same parameter values is unrealistic. Well-known covariates of disease severity such as age,38 chronic alcohol use,39, 40 starvation or malnutrition,41 and interactions with other drugs42, 43, 44 may affect the parameter values of an individual. In some cases these differences will not affect the accuracy of predictions of outcome. Model predictions derive from the amount of unconjugated NAPQI that results from a given dose, but that amount may depend on patient characteristics. For example, alcoholics may make excessive NAPQI because of elevated p-450 levels, or individuals may have decreased levels of GSH because of starvation, competition from other drugs, Obeticholic Acid cell line or genetic variation. These differences might make the model estimates of initial dose seem overly high, but the outcome could still be accurately predicted because these patients have

more unconjugated NAPQI than is typical for the overdose amount. James et al.45 show that APAP protein adduct levels may be used as specific biomarkers of APAP toxicity. If measurements were routinely available, adducts could easily be added to our model, and might provide additional this website predictive value. However, the correlation of protein adducts with AST and their similar kinetics lead us to predict this effect would be small, although their more direct relationship to liver damage might reduce noise and make them a superior predictor. Gregory et al.46 found that individuals with overdose amounts greater than 10 g did not have significantly different mortality than those reporting smaller overdoses in patients with eventual hepatic encephalopathy. The authors suggest that this may be due to inaccurate reporting of dosing information by patients with eventual hepatic encephalopathy, or from a plateau effect in APAP overdose amount, such that above a threshold the effect of APAP overdose ceases to be additive. A plateau is built into our model, but at 20 g rather than 10 g.