Background and Aims: Celiac disease (CD) is increasingly recognized as a driver of metabolic alterations and liver dysfunction, also after initiation of the gluten-free diet (GFD). Our aim was to evaluate the metabolic profile and hepatic steatosis prevalence in patients with CD at diagnosis compared with those on long-term GFD. Methods: We conducted an observational cross-sectional study with an exploratory longitudinal analysis, including adult CD patients evaluated either at diagnosis (CD_new group) or during follow-up after at least 24 months of self-reported adherence to GFD (CD_GFD group); a non-CD patient group, who underwent the same diagnostic pathway but in whom CD was excluded, was used as control. Patients with diabetes and other chronic liver diseases were excluded. Clinical, metabolic, and hepatic parameters were assessed, including lipid profile, fasting glucose, and liver steatosis, determined by abdominal ultrasound and transient elastography with controlled attenuation parameter (CAP). Steatosis was defined as CAP ≥ 248 dB/m. Results: A total of 85 patients were included (27 CD_new, 40 CD_GFD, 18 non-CD controls). Patients in the CD_GFD group had higher body mass index compared with CD_new (24.5 vs. 21.9 kg/m2), while age and sex distribution were similar. Total cholesterol was numerically higher in CD_GFD (183.1 vs. 172.9 mg/dL), whereas triglycerides, HDL-C, and LDL-C were comparable between groups. Fasting glucose levels were similar and within the normoglycemic range. Hepatic steatosis was numerically more prevalent in CD_GFD, with ultrasound-defined steatosis observed in 37.5% compared to 25.9% in CD_new and 33.3% in non-CD controls without reaching statistical significance. CAP-defined steatosis was present in 32.5% of CD_GFD patients versus 18.5% in CD_new and 33.3% in non-CD controls, with numerically higher mean CAP values in the follow-up group (217 vs. 204 dB/m). In the exploratory longitudinal subset (n = 10), median CAP increased from 182.5 to 217.0 dB/m (p = 0.047). Sensitivity analysis using higher CAP thresholds showed that higher-grade steatosis was observed more frequently in GFD-treated patients. Liver stiffness measurements were similar between groups (4.3, 4.5, and 4.9 kPa, respectively). Conclusions: Long-term GFD-treated CD patients had higher BMI and numerically higher hepatic steatosis prevalence, although steatosis differences were not statistically significant and GFD-treated status was not independently associated with CAP-defined steatosis after adjustment. CD patients may present distinct metabolic profiles from diagnosis to long-term follow-up.
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