Reply: Cigarette Smoking Is Not Associated with Specific Histological Features or Severity of Nonalcoholic Fatty Liver Disease^†

We thank Dr. Yilmaz et al. for their interest in our recent study published in HEPATOLOGY.1 As the authors described in their letter, our experimental study showing that cigarette smoking exacerbates nonalcoholic fatty liver disease (NAFLD) should be confirmed in human studies. In their letter, Yilmaz et al. show the results from a cross-sectional study including 90 patients with histologically-proven NAFLD. The logistic regression analysis showed that cigarette smoking was not an independent factor associated with the severity of NAFLD, after adjusting for sex, age, BMI and other factors. The authors conclude that cigarette smoking per se does not worsen the severity of NAFLD.

Although we acknowledge the effort of the authors to address this issue, we think that their observations are too preliminary to reach such strong conclusion. First, NAFLD is a highly heterogeneous disease that involves many environmental and genetic factors and the series from Yilmaz et al. is clearly underpowered because it only includes 90 patients. Large epidemiological studies including a high number of well-characterized patients are clearly needed to elucidate the role of smoking on NAFLD. And second, the impact of total number of pack-years smoked on the development of severe forms of NAFLD according to Kleiner's classification (i.e., definitive nonalcoholic steatohepatitis) should be specifically investigated. In conclusion, carefully designed clinical studies including large number of patients are required to assess the role of smoking on the clinical course of NAFLD.