Statins, antidiabetic medications and liver histology in patients with diabetes with non-alcoholic fatty liver disease.
BACKGROUND
Type-2 diabetes mellitus (T2DM) is a risk factor for progressive non-alcoholic fatty liver disease (NAFLD). Drugs commonly prescribed in patients with T2DM may affect liver histology by interfering with lipid metabolism and insulin resistance/secretion.


OBJECTIVE
We studied if statins or antidiabetic agents were associated with non-alcoholic steatohepatitis (NASH) and significant fibrosis (SF).


METHODS
We performed a cross-sectional study of 346 diabetics with biopsy-proven NAFLD. T2DM was defined as fasting glucose ≥7 mmol/L or glycated haemoglobin ≥6.5% and/or use of antidiabetics. NASH was defined according to the FLIP algorithm and SF as F2-4 Kleiner's stages.


RESULTS
84% of patients were on antidiabetic therapy and 45% on statins. NASH and SF were present in 57% and 48% of patients. Statin-treated patients were older, more frequently male and with poorer glycaemic control despite more frequent antidiabetic therapy than those without statins; however, the prevalence of NASH (57%vs56%, p=0.868) and SF (48%vs48%, p=0.943) was not different between statin users and non-users. NASH was more common in patients on metformin or insulin than in those not treated with these drugs (60%vs47%, p=0.026; 68%vs53%, p=0.017). SF was more common in those treated with sulfonylureas (57%vs44%, p=0.030). Multivariate analyses confirmed that use of statins was independently and negatively associated with both NASH (OR (95% CI) 0.57 (0.32 to 1.01), p=0.055) and SF (OR (95% CI) 0.47 (0.26 to 0.84), p=0.011). Moreover, we found independent associations between insulin use and NASH (OR (95% CI) 2.24 (1.11 to 4.54), p=0.025) and sulfonylureas use and SF (OR (95% CI) 2.04 (1.11 to 3.74), p=0.022).


CONCLUSIONS
Several medications used in patients with diabetes are differently associated with NAFLD histology. Statin use is negatively associated, while insulin and sulfonylureas are positively associated with NASH and SF. A wider use of statins may be warranted in this high-risk population.
Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy; Service d'Hépatogastroentérologie, Paris, France.
Fabio
F
Nascimbeni
Institute for Cardiometabolism and Nutrition (ICAN) , Paris , France.
Judith
J
Aron-Wisnewsky
Service d'Hépatogastroentérologie , Paris , France.
Raluca
R
Pais
Institute for Cardiometabolism and Nutrition (ICAN) , Paris , France.
Joan
J
Tordjman
Institute for Cardiometabolism and Nutrition (ICAN) , Paris , France.
Christine
C
Poitou
Department of Pathology , Hôpital Pitié Salpetrière, Assistance Publique Hôpitaux de Paris, Université Pierre et Marie Curie , Paris , France.
Frederic
F
Charlotte
Pathology Department , Beaujon Hospital, University Paris Diderot , Paris , France.
Pierre
P
Bedossa
Service d'Hépatogastroentérologie , Paris , France.
Thierry
T
Poynard
Institute for Cardiometabolism and Nutrition (ICAN) , Paris , France.
Karine
K
Clément
Service d'Hépatogastroentérologie , Paris , France.
Vlad
V
Ratziu
DIABETES MELLITUS; FATTY LIVER; FIBROSIS; LIPIDS; NONALCOHOLIC STEATOHEPATITIS