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.

As pointed out by Dr. Kittisupamongkol, the use of statins can cause abnormal aminotransferase levels. Because NHANES III was conducted from 1988 to 1994, only 4.8% of participants reported taking lipid-lowering medications. Use was not associated with elevated liver enzyme levels or their within-person variability in our study.

Drs. Hong, Wu, and Fan raise an important question regarding factors that affect intraindividual variability. However, our paper focused on describing the intraindividual variability in liver test results in the U.S. population. Further studies are needed to examine factors that may contribute to variability in liver enzyme levels across individuals.

As Drs. Colli and Prati mention, one should certainly be cautious when drawing practice recommendations from epidemiologic studies. The development of guidelines for the reporting of observational studies, such as STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) (4), was the result of similar concerns and the appreciation that much of our clinical and population-based knowledge has been derived from observational studies. We took advantage of a large, multiracial sample of the U.S. population, with a vast amount of rigorously collected data. This study would have been very difficult to conduct otherwise.