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Peter Lemmer, Nicole Selbach, Theodor Baars, Mustafa Porsch-Özcürümez, Dominik Heider, Ali E. Canbay, Jan-Peter Sowa

• \(\bf Background:\) In current general practice, elevated serum concentrations of liver enzymes are still regarded as an indicator of non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH). In this study, we analyzed if an adjustment of the upper limit of normal (ULN) for serum liver enzymes can improve their diagnostic accuracy. \(\bf Methods:\) Data from 363 morbidly obese patients (42.5 \(\pm\) 10.3 years old; mean BMI: 52 \(\pm\) 8.5 kg/m\(^{2}\)), who underwent bariatric surgery, was retrospectively analyzed. NAFL and NASH were defined histologically according to non-alcoholic fatty liver activity score (NAS) and according to steatosis activity fibrosis (SAF) score for 2 separate analyses, respectively. \(\bf Results:\) In 121 women (45%) and 45 men (46%), elevated values for at least one serum parameter (ALT, AST, \(\gamma\)GT) were present. The serum concentrations of ALT (\(\it p\) < 0.0001), AST (\(\it p\) < 0.0001) and \(\gamma\)GT (\(\it p\) = 0.0023) differed significantly between NAFL and NASH, irrespective of the applied histological classification method. Concentrations of all 3 serum parameters correlated significantly positively with the NAS and the SAF score, with correlation coefficients between 0.33 (ALT/NAS) and 0.40 (\(\gamma\)GT/SAF). The area under the curves to separate NAFL and NASH by liver enzymes achieved a maximum of 0.70 (ALT applied to NAS-based classification). For 95% specificity, the ULN for ALT would be 47.5 U/L; for 95% sensitivity, the ULN for ALT would be 17.5 U/L, resulting in 62% uncategorized patients. \(\bf Conclusion:\) ALT, AST, and γGT are unsuitable for non-invasive screening or diagnosis of NAFL or NASH. Utilizing liver enzymes as an indicator for NAFLD or NASH should generally be questioned.