Author information

¹Division of Gastroenterology, Hepatology and Nutrition; Department of Medicine, University of Louisville, Louisville, KY, 40202, USA; The Liver Transplant Program at UofL Health - Jewish Hospital Trager Transplant Center, Louisville, KY, 40202, USA. Electronic address: slcondon25@gmail.com.

²Department of Bioinformatics and Biostatistics, University of Louisville, Louisville, KY, 40202, USA. Electronic address: huirong.hu@louisville.edu.

³Department of Bioinformatics and Biostatistics, University of Louisville, Louisville, KY, 40202, USA. Electronic address: maiying.kong@louisville.edu.

⁴Division of Gastroenterology, Hepatology and Nutrition; Department of Medicine, University of Louisville, Louisville, KY, 40202, USA; The Liver Transplant Program at UofL Health - Jewish Hospital Trager Transplant Center, Louisville, KY, 40202, USA; University of Louisville Alcohol Research Center, Louisville, KY, 40202, USA; Hepatobiology & Toxicology Center, Louisville, KY 40202, USA; Robley Rex VA Medical Center, Louisville, KY, 40206, USA. Electronic address: matt.cave@louisville.edu.

⁵Division of Gastroenterology, Hepatology and Nutrition; Department of Medicine, University of Louisville, Louisville, KY, 40202, USA; The Liver Transplant Program at UofL Health - Jewish Hospital Trager Transplant Center, Louisville, KY, 40202, USA; University of Louisville Alcohol Research Center, Louisville, KY, 40202, USA; Hepatobiology & Toxicology Center, Louisville, KY 40202, USA; Robley Rex VA Medical Center, Louisville, KY, 40206, USA. Electronic address: craig.mcclain@louisville.edu.

Abstract

Background: Non-alcoholic fatty liver disease is a growing problem in the United States, contributing to a range of liver disease as well as cardiovascular disease. ALT is the most widely used liver chemistry for NAFLD evaluation. We hypothesized that the normal range many laboratories use was too high, missing many patients with clinically important steatosis and/or fibrosis.

Methods: This study utilized 2017-2018 NHANES data including 9,254 participants. We compared four different upper limits of normal for ALT with specific measurements of steatosis and liver stiffness as determined by liver elastography with FibroScan®. Liver stiffness was further characterized as showing any fibrosis or advanced fibrosis. After exclusions, our final pool was 4,184 for liver stiffness measurement and 4,183 for steatosis grade as measured by Controlled Attenuation Parameter (CAP). Using these variables, we performed logistic regression between ALT and CAP, and ALT and fibrosis/advanced fibrosis, and did a Receiver Operating Characteristic curve.

Results: Based on three of the most widely used cut off values for ALT, we found that ALT does not reliably rule out NAFLD in over 50% of cases. It also missed 45.9-64.2% of patients with liver fibrosis.

Conclusions: Our study revealed that ALT is an inaccurate marker for NAFLD as measured by FibroScan® with CAP greater than or equal to 300 dB/m. Accuracy improved specific risk factors were considered. These data also showed that ALT was a poor marker for liver fibrosis. We conclude that there is no single ALT level that accurately predicts hepatic steatosis or fibrosis.