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Insulin resistance, other factors associated with high ALT levels in NAFLD, NASH

In a prospective study, patients with nonalcoholic fatty liver disease and nonalcoholic steatosis who had high levels of alanine aminotransferase also had high levels of insulin resistance and liver triglyceride content.

Researchers divided 440 overweight and obese patients with and without NAFLD into three groups: those without NAFLD (n=60), those with NAFLD and normal ALT levels (n=165), and those with NAFLD with high ALT levels (n=215). They measured liver fat using proton magnetic resonance spectroscopy, severity of liver disease through a biopsy (n=293) and insulin sensitivity in liver, muscle and adipose tissue through use of a euglycemic hyperinsulinemic clamp with [3-³H]glucose.

The patients with NAFLD and high ALT levels had worse adipose tissue insulin resistance (ATIR; P<.0001) compared with patients with NAFLD and normal levels, as well as higher liver triglyceride content (26.8% vs. 17.9%; P<.0001), higher insulin and free fatty acid levels and lower plasma adiponectin levels (P<.05).

Among patients with NASH and high ALT levels, liver triglyceride content was worse compared with patients with only NASH (29% vs. 20.5%; P<.0001). In addition, steatosis on liver biopsy was higher in patients with NASH and high ALT levels (2.2 grade vs. 1.6 grade; P<.0001).   

There were no differences observed in ballooning, inflammation or fibrosis among all groups of patients, according to the research.

“Our findings suggest that severe ATIR with liver triglyceride accumulation plays a crucial role to the clinical observation of increased plasma ALT in both NAFLD and steatohepatitis,” the researchers wrote. “These results deserve confirmation in future studies, but suggest that plasma ALT levels are poor surrogate markers of disease activity and should be interpreted, being aware of limitation in those suspected of having NAFLD.”

Disclosure: The researchers report no relevant financial disclosures.