We thank Dr. Holt for his interest in our study investigating associations between ethnicity and nonalcoholic fatty liver disease (NAFLD) using data from the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN), and we appreciate the positive comments regarding our study made by Dr. Holt in his letter.1
Dr. Holt reiterates the importance of 2 key variables related to the analysis of NAFLD histologic severity, namely age and the role of the PNPLA3 rs738409 polymorphism that we had described in detail in the Discussion section of our article. We welcome Dr. Holt's reemphasis of our initial points. With respect to age, this is indeed a well-recognized risk factor associated with fibrosis in NASH. We specifically noted in our Discussion that “the lower frequency of advanced fibrosis may be explained, at least in part, by the overall younger age of the Latino population in [our] study.”2-4 Additionally, as we stated in the original article, our investigation used a cross-sectional design, and therefore was not intended to address the fate of the patients at a more advanced age. Addressing this particular issue will require longitudinal follow-up and data collection, which may become feasible with ongoing and future follow-up of patients in the NASH CRN. With respect to the role of the PNPLA3 rs738409 polymorphism in the pathogenic differences between Latino and non-Latino white individuals, our Discussion emphasized the highly important potential role of this genetic variation and cited several pertinent studies from the rapidly growing literature on this topic.5-9 We appreciate Dr. Holt's citing the important study by Speliotes et al.10 Notably, this study was based, in part, on the same population in the NASH CRN that formed the basis for our investigation, and which further points to the emerging relationship between PNPLA3 and the pathogenesis of NASH. Additional studies are currently underway in the NASH CRN and in other collaborative groups that should shed more light on the complex genetic influences in NAFLD and other liver diseases.