Drawing Conclusions about Short-Term Variability in Liver Function Test Results

IN RESPONSE:

We appreciate the readers' interest in our study. As indicated by Drs. Arora and Triadafilopoulos, because our study was based on a nonrandom sample of the NHANES III population, selection bias remains a possibility. However, even if selection bias were present, it doesn't change the fact that, although sociodemographic and other patient-level characteristics may be associated with the absolute level of liver enzymes, such factors are unlikely to affect variability, which is a biological phenomenon. Indeed, we did not observe differences in estimates of variability by demographic or other patient-level characteristics. We agree that because Asians make up only a very small percentage of the NHANES III study population (<5%), it is not possible to draw firm conclusions regarding this population. Results of analyses using the cutoffs for an ALT level of 19 IU/L or greater for women and 30 IU/L or greater for men were essentially identical (31% returned to normal); however, the prevalence of elevated ALT levels using these cutoffs is higher: 17% versus 6%. We agree that defining the reference range for liver tests is an important area of debate (1–3). Finally, although the Gilbert syndrome is a common cause of elevated bilirubin levels, to our knowledge no evidence suggests that it affects the within-person variability of liver enzyme levels. In addition, our results were unchanged when we excluded adults with recent illness or those who fasted more than 8 hours at both examinations.