Liver function tests as indicators of metabolic syndrome

Nonalcoholic fatty liver disease (NAFLD) is no longer considered to be a normal physiologic condition without any clinical significance. It is now widely accepted that nonalcoholic steatohepatitis (NASH), a type of fatty liver disease, can progress to end-stage liver disease and increase the risk of mortality. In addition, NAFLD patients are associated with a significantly higher overall mortality as well as liver-related mortality compared to the age-and gender-adjusted general population. 1,2 Accordingly, several studies have been conducted to redefine the normal ranges of liver function tests, especially alanine aminotransferase (ALT) levels considering the influence of NAFLD on serum ALT level. However, there are two different ways to interpret ALT levels. Piton et al suggested that these levels should be interpreted with respect to the body mass index (BMI) considering the positive association between ALT level and BMI. 3 However, this concept was questioned by Prati et al 4 since NAFLD itself is not necessarily a benign liver disease without clinical significance. The normal range of ALT levels is significantly lower than the conventional cutoff levels (41 IU/L for men and 30 U/L for women) if patients with risk factors for NAFLD are excluded. This finding was also observed in a Korean population in which patients with NAFLD were excluded histologically. 5 Another important study from Korea also showed a positive association between ALT level even within the normal range by conventional criteria and liver-related mortality. 6 All these findings suggested that the normal range of ALT level (along with those of other liver function test factors) should be adjusted. However, several points should be considered before applying the revised upper limit of normal serum ALT levels. A study by Oh et al 7 reported that the incidence of metabolic syndrome and NAFLD correlates with ALT and γ-glutamyltransferase (GGT) levels within the conventional reference ranges. About half of the subjects with ALT levels in the upper fourth quartile of the conventional normal range had fatty liver disease that appeared on ultrasonography. This finding strongly suggests that adjustment of the normal range for ALT level can increase the detection rates of patients with NAFLD. However, the study population consisted of individuals who underwent health checkups voluntarily, and therefore could have introduced selection biases. Another unanswered question is what proportion of patients with NAFLD actually has histologically-diagnosed NASH. It is generally accepted that liver-related mortality does not increase in patients with simple steatosis. …