Unraveling the Role of Hypothyroidism in Non-alcoholic Fatty Liver Disease Pathogenesis: Correlations, Conflicts, and the Current Stand

Non-alcoholic fatty liver disease (NAFLD) has become one of the most common causes of chronic liver diseases globally. Because thyroid hormones play a crucial role in lipid metabolism, thyroid dysfunction has been implicated in NAFLD pathogenesis in the past decade, with hypothyroidism-induced NAFLD being regarded as a distinct disease entity. However, there has been no common consensus yet, and several studies have found contradictory results. Hence, we conducted this systematic review to represent the current view on the role of hypothyroidism (HT) and individual thyroid function parameters such as thyroid-stimulating hormone (TSH), thyroxine (T4), triiodothyronine (T3), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TGAb) in NAFLD pathogenesis. We searched PubMed, PubMed Central, and Semantic Scholar databases from inception until January 2021 to identify relevant observational (case-control, cross-sectional, and longitudinal) studies. A total of 699 articles were recognized through our database search. After applying the eligibility criteria and performing quality assessment, 10 studies involving 42,227 participants were included in the final systematic review. Each of these studies assessed different thyroid function parameters, and NAFLD was found to be associated with HT in two studies, elevated TSH in three studies, suppressed T4 in three studies, elevated T3 in one study, and elevated TPOAb in one study. There was also a wide heterogeneity in HT definition, study population characteristics, and study design among these studies, making a direct comparison difficult. Because the recognition of HT-induced NAFLD has possible diagnostic, therapeutic, and prognostic implications, we recommend that comprehensive, long-term prospective studies be carried out to determine if HT or thyroid function parameters are causally associated with NAFLD.