Incidence of non-alcoholic fatty liver disease and metabolic dysfunction in first episode schizophrenia and related psychotic disorders: a 3-year prospective randomized interventional study

Rationale Patients with schizophrenia spectrum disorders have increased morbidity and mortality, largely due to cardiovascular disease, which is associated with antipsychotic treatment. Because of the link between cardiometabolic risk, non-alcoholic fatty liver disease (NAFLD), and antipsychotics, we aimed to investigate the development of NAFLD during the first 3 years of antipsychotic treatment in first episode non-affective psychosis patients. A sample of 191 subjects was included in final analyses, randomly assigned to aripiprazole (N = 83), risperidone (N = 12), quetiapine (N = 46), and ziprasidone (N = 50). At intake, 180 patients were antipsychotic na < ve. The NAFLD fibrosis score, FIB-4 score, and the fatty liver index (FLI) were calculated at baseline, at 3 months, and then yearly for 3 years. None of the patients showed significant liver fibrosis according to the mentioned scores at baseline, prior to randomization. At 3 years follow-up, 25.1 % individuals showed a FLI score aeyen60, which is a predictor of steatosis. Of the individuals considered indeterminate at baseline, 64.7 % developed a FLI score aeyen60 and only 16.6 % who had a FLI score < 30 at baseline, showed a FLI score predictor of steatosis at endpoint. The FLI score aeyen60 at endpoint was associated with an increase of more than 7 % of the body mass index (FLI score aeyen 60, 91.7 %; FLI < 60, 55.9 %; p < 0.001), increased triglyceride levels (FLI score aeyen 60, 54.2 %; FLI < 60, 5.6 %; p < 0.001), decreased HDL levels (FLI score aeyen 60, 41.7 %; FLI < 60, 17.5 %; p = 0.001), hypertension (FLI score aeyen 60, 19.5 %; FLI < 60, 4.5 %; p = 0.002), and waist circumference increase (steatosis 68.8 %; FLI < 60, 14.0 %; p < 0.001). Our results support the importance of assessing the potential development of NAFLD in schizophrenia spectrum patients receiving antipsychotic medication.