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Background/Aim <p>Celiac disease (CD) is frequently underdiagnosed in adults due to the absence of classic gastrointestinal symptoms, leading to delayed diagnosis and potential long-term complications. This study aimed to identify subtle clinical and laboratory indicators preceding CD diagnosis in young adults (18–40&#xa0;years).</p> Methodology <p>A retrospective cohort study was conducted using data from over 430,000 members of Clalit Health Services. Incident CD cases were identified by an ICD-9 code and a positive serological test. Laboratory values were analyzed for trends up to 7&#xa0;years prior to diagnosis, and “relative” abnormalities were defined based on medians of diagnosed CD patients. Cox proportional hazards regression was used to assess the association between various pre-diagnostic clinical, laboratory, factors and the risk of CD diagnosis for 10&#xa0;years.</p> Results <p>Relative lower hemoglobin and MCV in males and females were associated with CD with HR of 2.15 (1.43–3.22) and 5,519 (4.41–7.41) respectively. Liver enzymes (ALT more than 22 U/L in females and 27 U/L in males), and lower BMI even within the normal range, were significantly associated with an increased risk of later CD diagnosis with HR of 1.881 (1.29–2.75) for women and 2.919 (1.81–4.71) for males. These subtle laboratory and BMI findings were observable as early as 7&#xa0;years before formal diagnosis. Additionally, chronic gastrointestinal symptoms and chromosomal risk factors significantly preceded CD diagnosis.</p> Conclusion <p>Early recognition of subtle indicators like low normal hemoglobin, elevated liver enzymes, and lower BMI, alongside persistent GI symptoms and genetic predispositions, can enable timelier screening and diagnosis of CD in young adults, potentially mitigating long-term health consequences.</p>

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Subtle Laboratory and Clinical Precursors of Celiac Disease in Young Adults: A Large-Scale Retrospective Cohort Study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月23日

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  • Ramon Cohen,
  • Shay Nemet,
  • Alena Kirzhner,
  • Tal Schiller,
  • Haitham Abu Khadija,
  • Shira Bezalel-Rosenberg,
  • Ilan Asher,
  • Ali Abdallah,
  • Keren Mahlab-Guri,
  • Daniel Elbirt

摘要

Background/Aim

Celiac disease (CD) is frequently underdiagnosed in adults due to the absence of classic gastrointestinal symptoms, leading to delayed diagnosis and potential long-term complications. This study aimed to identify subtle clinical and laboratory indicators preceding CD diagnosis in young adults (18–40 years).

Methodology

A retrospective cohort study was conducted using data from over 430,000 members of Clalit Health Services. Incident CD cases were identified by an ICD-9 code and a positive serological test. Laboratory values were analyzed for trends up to 7 years prior to diagnosis, and “relative” abnormalities were defined based on medians of diagnosed CD patients. Cox proportional hazards regression was used to assess the association between various pre-diagnostic clinical, laboratory, factors and the risk of CD diagnosis for 10 years.

Results

Relative lower hemoglobin and MCV in males and females were associated with CD with HR of 2.15 (1.43–3.22) and 5,519 (4.41–7.41) respectively. Liver enzymes (ALT more than 22 U/L in females and 27 U/L in males), and lower BMI even within the normal range, were significantly associated with an increased risk of later CD diagnosis with HR of 1.881 (1.29–2.75) for women and 2.919 (1.81–4.71) for males. These subtle laboratory and BMI findings were observable as early as 7 years before formal diagnosis. Additionally, chronic gastrointestinal symptoms and chromosomal risk factors significantly preceded CD diagnosis.

Conclusion

Early recognition of subtle indicators like low normal hemoglobin, elevated liver enzymes, and lower BMI, alongside persistent GI symptoms and genetic predispositions, can enable timelier screening and diagnosis of CD in young adults, potentially mitigating long-term health consequences.