November 2023
Nonalcoholic steatohepatitis and fibrosis in patients with ‘normal’ ALT levels

In patients with type 2 diabetes, these conditions were surprisingly common even when ALT was lower than 40 IU/L. 

Recent data suggest that nonalcoholic fatty liver disease (NAFLD) is underdiagnosed when thresholds of about 40 IU/L for serum alanine or aspartate aminotransferase (ALT or AST) are used to trigger evaluation. In this study, French researchers performed liver biopsies in 330 patients with type 2 diabetes who had suspected NAFLD based on either elevated transaminases or steatosis on ultrasound. One-third of patients had ALT levels lower than 40 IU/L (but 20 IU/L or more for women and 30 IU/L or more for men). Patients who drank alcohol excessively and patients with other hepatic diagnoses were excluded.

Median age was 59 years, and median body mass index was 32 kg/m2. Liver biopsy revealed nonalcoholic steatohepatitis (NASH) in 58% of patients and advanced fibrosis in 38%. On average, patients with NASH or advanced fibrosis had higher ALT levels than patients without those diagnoses, but one-quarter of patients with NASH or advanced fibrosis had ALT levels lower than 40 IU/L. The authors present additional data on the accuracy of combinations of laboratory tests and transient elastography to predict NASH and advanced fibrosis.

Comment: The prevalence of liver disease in this patient population was striking. However, we do not know whether routine screening for NAFLD in patients with type 2 diabetes and ‘normal’ transaminases ultimately would improve long-term outcomes. The cornerstone of initial management of NAFLD in patients with type 2 diabetes is weight reduction and good glycaemic control – which we already would recommend for overweight patients with type 2 diabetes. But if highly effective drug therapies to reverse NASH and fibrosis eventually are approved, more intensive case-finding will likely be worthwhile.

Allan S. Brett, MD, Clinical Professor of Medicine, University of Colorado School of Medicine, Aurora, USA.

Castera L, et al. High prevalence of NASH and advanced fibrosis in type 2 diabetes: a prospective study of 330 outpatients undergoing liver biopsies for elevated ALT, using a low threshold. Diabetes Care 2023; 46: 1354-1362.

Scoditti E, et al. Hunting for progressive NAFLD in type 2 diabetes: do not trust liver enzymes! Diabetes Care 2023; 46: 1332-1334.

This summary is taken from the following Journal Watch titles: General Medicine, Ambulatory Medicine, Gastroenterology.

Diabetes Care