Is biopsy necessary for celiac patients?

Background and Aim: Celiac disease is an autoimmune enteropathy triggered by gluten in genetically susceptible individuals, with a global prevalence of 0.5-2%. Although serologic tests are widely used in diagnosis, duodenal biopsy remains the gold standard; however, its invasive and costly nature highlights the need for non-invasive diagnostic approaches. This study aimed to evaluate clinical and laboratory parameters in biopsy confirmed celiac cases and to determine an optimal anti-tissue transglutaminase IgA threshold that may support a non-invasive diagnostic strategy. Material and Method: This retrospective study included patients ≥18 years of age who presented to the Gastroenterology Department of Çukurova University between 2018 and 2024 and had positive anti-tissue transglutaminase IgA results. Demographic characteristics, clinical findings, serologic data and duodenal biopsy results were reviewed from electronic records. Patients with at least four biopsies taken from the second part of the duodenum and the bulb were included. Biopsies were evaluated according to the Marsh classification, and celiac disease was confirmed based on European guideline criteria, incorporating serology, histology, and dietary response. In serology-positive but biopsy-negative cases, HLA-DQ2/DQ8 testing was assessed, and serology or biopsy was repeated when necessary. Results: A total of 196 patients were evaluated in this study, and individuals with celiac disease (n=99) were compared with non-celiac controls (n=97) in terms of demographic, clinical, laboratory, and histological characteristics. The mean age was significantly lower in the celiac group (p=0.013). Anti-tissue transglutaminase IgA titers were markedly higher, whereas ferritin levels were significantly lower in patients with celiac disease (both p<0.001). No significant difference was observed between the groups regarding vitamin B12 levels. Histologically, 77.3% of the control group exhibited Marsh 1 findings, while all patients with celiac disease demonstrated Marsh 3 villous atrophy (p<0.001). According to the ROC analysis, an anti-tissue transglutaminase IgA threshold of >62 IU/mL yielded a sensitivity of 76.8% and a specificity of 100%, indicating high diagnostic accuracy. Among patients with iron deficiency, diarrhea, weight loss, and more advanced histological damage were observed more frequently, and ferritin levels were significantly lower (p<0,001). Duodenal histology further showed that Marsh 1 lesions were more common in individuals without iron deficiency (p=0.029), whereas advanced villous atrophy (Marsh 3C) was more frequently observed in those with iron deficiency; however, this difference did not reach statistical significance. Conclusion: Our study provides important contributions to the current debate regarding the necessity of biopsy in the diagnosis of celiac disease by integrating serological, histological, and clinical findings. Notably, the 100% specificity observed for an Anti-dTG IgA level >62 IU/mL suggests that a biopsy-free diagnostic approach in adults will be increasingly discussed in the future and that new threshold values may eventually be incorporated into clinical practice. Nevertheless, prospective, multicenter studies are needed to further clarify this issue. Keywords: Anti-transglutaminase IgA, celiac disease, duodenal biopsy, Marsh classification