Psychotropic Medications Are Associated With Increased Liver Disease Severity in Pediatric Nonalcoholic Fatty Liver Disease

Abstract

Objectives: The aim of the study was to determine whether pediatric patients with nonalcoholic fatty liver disease (NAFLD) exposed to psychotropic medications have more severe liver disease compared to their counterparts who are not on these medications. We hypothesize that use of psychotropic agents is associated with liver disease severity. Methods: Children and adolescents with biopsy-confirmed NAFLD were included in this study. Histology data, detailed clinical information, and results of serum biochemistries performed within 3 months of the liver biopsy were collected retrospectively. Univariate and multivariate modeling was used to determine differences between the groups and to control for confounders. Results: A total of 228 patients were included, 17 (8%) of whom where on psychotropic medications at the time of the liver biopsy. Patients on psychotropic medications were more likely to also be on metformin (53% vs 18%, P < 0.01) and antihypertensive medications (29% vs 8%, P < 0.01) compared to children with NAFLD who were not on psychotropic agents. There were no differences in regards to biochemical evidence of liver injury, insulin resistance, and dyslipidemia between the groups. On histology, however, the use of psychotropic medications was associated with increased steatosis severity (score 2.4 vs 1.9, P = 0.04) and increased likelihood of having an NAFLD Activity Score ≥5 (seen in 59% vs 35% or patients; P = 0.05, respectively). Conclusions: In this large cohort of children with biopsy-confirmed NAFLD, the use of psychotropic medications was associated with increased liver disease severity. Exposure to psychotropic agents should be considered when risk stratifying children with NAFLD.

Understanding Mechanisms Underlying Non-Alcoholic Fatty Liver Disease (NAFLD) in Mental Illness: Risperidone and Olanzapine Alter the Hepatic Proteomic Signature in Mice

“…Patients with severe mental illness, including schizophrenia, experience a significantly shortened life expectancy with high rates of all-cause mortality [1][2][3], most commonly associated with metabolic dysregulation and cardiovascular disease. Non-alcoholic fatty liver disease (NAFLD) is a growing epidemic worldwide and is associated with obesity, insulin resistance, and inflammation [4][5][6][7]. Incidence of NAFLD is elevated in patients with severe mental illness [3] and with atypical antipsychotic (AA) treatment [8].…”

“…Although the clinical literature describes relative risks and contributions of intrinsic and extrinsic effects on metabolic disorders in schizophrenia [15][16][17], underlying mechanisms in both schizophrenic and non-schizophrenic patients remain elusive. Patients prescribed antipsychotic medications experience significant endocrine and metabolic side effects including weight gain, insulin resistance, hyperglycemia, dyslipidemia, hyperprolactinemia, and bone loss, regardless of diagnosis [6,18]. Broadly stated, AA side effects appear to be mediated both by global (i.e., the central nervous system) and tissue-specific mechanisms, including those in the liver.…”

Significance of autoantibody seropositivity in children with obesity and non‐alcoholic fatty liver disease

“…1 Conversely, in the absence of autoantibody positivity, at our institutions, patients undergo liver biopsies if there are concerns that they may have more severe NAFLD (steatohepatitis, advanced fibrosis), as suggested by the presence of multiple cardiometabolic risk factors (eg, dyslipidemia, T2DM etc.) 4,22 or significantly and persistently elevated levels of serum aminotransferases. 1,12 Interestingly, in spite of the lower aminotransferase levels seen in children with positive autoantibodies, those with positive ANA were more likely to have severe steatosis than those with negative ANA.…”

“…Conversely, in the absence of autoantibody positivity, at our institutions, patients undergo liver biopsies if there are concerns that they may have more severe NAFLD (steatohepatitis, advanced fibrosis), as suggested by the presence of multiple cardiometabolic risk factors (eg, dyslipidemia, T2DM etc. ) 4,22 or significantly and persistently elevated levels of serum aminotransferases 1,12 …”

Can Baseline Characteristics be Used to Predict Liver Disease Outcomes in Pediatric Nonalcoholic Fatty Liver Disease?

“…Both adult and pediatric cross‐sectional studies have uncovered variables associated with NAFLD severity. Known factors linked to more severe disease include male sex, Hispanic ethnicity, genetic predisposition (e.g., PNPLA3, hypobetalipoproteinemia), psychotropic medication usage, obstructive sleep apnea, obesity severity, and presence of insulin resistance or type 2 diabetes (4‐11). More recently, we have recognized the impact of neighborhood‐level stress and socioeconomic status (SES) on NAFLD (12,13).…”