Psoriasis and steatotic liver disease: Are PNPLA3 and TM6SF2 polymorphisms suitable for the hepato-dermal axis hypothesis?

Introduction and Objectives: A high prevalence of steatotic liver disease has been described in psoriasis. However, the influence of genetic polymorphisms has yet to be investigated in this scenario. This study aims to determine the frequency of steatosis, advanced liver fibrosis and PNPLA3/TM6SF2 genotypes in individuals with psoriasis and to evaluate the impact of genetic polymorphisms, metabolic parameters and cumulative methotrexate dose on steatosis and fibrosis. Materials and Methods: Cross-sectional study that prospectively included psoriasis outpatients, submitted to clinical and laboratory analysis, transient elastography (FibroScan (R), Fr) and PNPLA3/TM6SF2 genotyping. Steatosis was defined by CAP >= 275 dB/m and advanced liver fibrosis as transient elastography >= 10 kPa. Logistic regression analysis evaluated the independent variables related to steatosis and fibrosis; p-value< 0.05 was considered significant. Results: One hundred and ninety-nine patients were enrolled (age 54.6 +/- 12.6 years, 57.3% female). Metabolic syndrome (MetS), steatosis and advanced liver fibrosis prevalence were 55.8%, 54.8% and 9%, respectively. PNPLA3 and TM6SF2 genotypes frequencies were CC 42.3%/CG 49.5%/GG 8.2% and CC 88.7%/ CT 11.3%/ TT 0%. MetS (OR3.01 95%CI 1.51-5.98; p = 0.002) and body mass index (OR1.17 95%CI 1.08-1.26; p < 0.01) were independently associated with steatosis. Diabetes Mellitus (T2DM) (OR10.76 95%CI 2.42-47.87; p = 0.002) and harboring at least one PNPLA3 G allele (OR5.66 95%CI 1.08-29.52; p = 0.039) were associated with advanced fibrosis, but not TM6SF2 polymorphism or cumulative MTX dose. Conclusions: MetS and T2DM confer higher odds for steatosis and advanced fibrosis in individuals with psoriasis. PNPLA3 G allele, but not TM6SF2 polymorphism, impacts a 5-fold odds of advanced liver fibrosis. (c) 2024 Fundacion Clinica Medica Sur, A.C. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)