Liver-Function Test Changes with Substantial Weight Loss

Nonalcoholic fatty liver disease (NAFLD) is increasing in prevalence and is linked to obesity and insulin resistance. Its severity can range from benign steatosis to cirrhosis and effective treatment has not been established. Steatosis is reported in 67% of obese individuals and 90% of severely obese individuals (NEJM 346:1221, 2002). While nutritional approaches are recommended, there are concerns about rapid weight loss. We systematically assessed liver function tests (LFTs) every 2-4 weeks in two groups of patients losing substantial weight in a fairly rapid manner. The first group included 118 patients with severe obesity (SO, BMI >40 kg/m2) who lost 100 pounds (#) in 27 weeks and the second group included 91 obese (Ob) individuals (BMI 30-82, mean 47 kg/m2) who lost 40# in 18 weeks. The SO and Ob patients enrolled in the Health Management Resources® (HMR®) Program at the University of Kentucky and were treated with low-energy diets in an intensive behavioral program utilizing meal replacement shakes and entrees. This report will focus on alanine (ALT) and aspartate (AST) aminotransferase values. Elevated ALT and ALT/AST ratios have been most linked to liver fat accumulation. At baseline, elevated ALTs were seen in 25% of SO and 26% of Ob; ALT/AST ratios were >1 in 78% of SO and 74% of Ob. LFTs were available for 80% of SO for 40 wks during mean weight losses of 132 lbs. In 70 patients with baseline ALT <40 units, values increased from 25 to 60 U at 6 wks and then decreased to 30U by 16 wks and to <baseline by 40 wks. Mean peak and final values were 81 and 24 U. In 24 patients with abnormal initial values, values increased from 61 to 81 U at 2 wks then decreased steadily to 34 U by 16 wks. Mean peak and final values were 97 and 28
U. ALT increases of >50% of baseline or to above 50 U were seen in 96% of patients. In 8 patients ALTs exceeded 100U (112-856U) in 4-8 weeks but 6 returned to <40U by 40 wks; 2 had values of 44 and 77 U at 40 wks and negative hepatitis serology. The Ob patients had mean initial and final ALTs of 33 and 29 U. With weight losses of 3-6#/wk and monitoring, our patients had transient increases in LFTs with subsequent return to normal by 16 weeks in 98%. These observations suggest most of our patients had benign steatosis that benefited from rapid and significant weight loss.