Prof. Dr. Giuseppe Magazzu

Prof. Dr. Dušanka Mičetić-Turk

and all

Progress of the Prospective study - Medicel

Background

Celiac disease (CD)has increased at an unexpected rate in the last two decades not only in Europe but also in Mediterranean regions.

The consequences of unrecognized CD can be severe particularly with regard to mortality and morbidity among these patients.

The aims of study:

To identify the factors that may influence the onset of CD in Mediterranean basin

To identify clinical and laboratory data which can predict the diagnosis of the disease

To determine where the new ESPGHAN diagnostic criteria could be applied and what % of patients can omitt the biopsy

Service and survey design: Prospective cohort observational survey

Duration: April 2013 to March 2014

Setting: 13 CD centers from 12 Mediterranean countries:Albania, Algeria, Croatia, Egypt, Greece, Italy,Malta, Montenegro, Morocco, Slovenia, Tunisia, Turkey

Sample: unselected new cases referred for suspected CD

Patients

Data of patients were collected and put into a web-based database of Medicel Mediterranean Network (www.medicel.unina.it/)

Which data were collected?

• Pregnancy duration and outcome• Birth weight• Breastfeeding• Age of gluten introduction into the diet• Number of previous admissions to hospital• Clinical symptoms (main, second and third)• Familiarity• Associated diseases

Which data were collected?

• Antitransglutaminase antibodies IgA (t-TG) as Nx upper limit of normal (ULN)

• Endomysial antibodies (EMA)• HLA-DQ2/DQ8• Histology (Marsh-Oberhuber classification)• DNA, sera and tissue frozen samples were

collected for further studies• Follow-up to confirm uncertain case

Statistics

Crosstabs and stepwise statistics were generated by SPSS and t-Test, Odds Ratio (OR) and Positive Predictive Value (PPV) were estimated for variables.

Results of the study

Country Total CD NCD

Albania 31 28 3

Algeria 31 21 10

Croatia 9 8 1

Egypt 20 15 5

Greece 35 29 6

Italy-Me 270 100 170

Italy-Na 339 196 143

Malta 10 9 1

Monten. 8 8 0

Morocco 85 49 36

Slovenia 61 31 30

Tunisia 41 20 21

Turkey 104 23 81

PATIENTS ENROLLED INTO THE STUDY

Results

1044 patients enrolled 537 CD

In 460 gold standard intestinal biopsy In 77 gold standard EMA positive

507 NCD 491 NCD 16 potential CD (15 EMA positive)

Results

Duration of gestation and breastfeeding were significantly longer in CD

NCD had a heavier birth weight No difference was found for age of

gluten introduction and number of previous hospital admissions

ResultsSymptoms PPV (95% CI) OR (95% CI)

Anorexia/lack of appetite

73% (62-81) 2.74 (1.64-4.60)

Abdominal distention

68% (60-76) 2.30 (1.55-3.42)

Anemia 63% (53-71) 1.71 (1.11-2.63)

Vomit 54% (48-62) 1.50 (1.07-2.10)

Abdominal pain 63% (53-71) 0.66 (0.50-0.87)

Contipation 37% (30-44) 0.51 (0.35-0.74)

Familiarity and associated diseases

CD NCD

Famil. 117 83

No Famil 306 411

CD NCD

As. Dis. 104 80

No As. Dis

425 435

Familiarity OR 1.89(1.38-2.6) Ass. Diseases OR 1.33 (0.97-1.83)

Results PPV of tTGA > 10 x ULN: 0.951 (95% CI:0.922-

0.969); LR+ = 21.1 (95%CI: 13.0-34.37). Out of 537 CD, in 77 no biopsy

Out of 460 pts with M2-3, 308 (67%) had tTGA > 10 x ULN: 78 no EMA

230 (50%) EMA positive with M 2-3 might have avoided intestinal biopsy according to ESPGHAN NGL

4.6% with tTGA > 10 x ULN (EMA positive) had a potential CD.

Conclusion This large prospective study provides for the

first time PPV, that is the pre-test probability, of symptoms.

Based on tTGA diagnostic accuracy obtained in own laboratory, single centers can make clinical decision on if and when intestinal biopsy may be omitted, according to the new ESPGHAN guidelines.

There is a chance to meet potential CD even in the presence of a tTGA > 10 x ULN value.

Conclusion

The results of the study raises many questions, the most important:

• Is it ever justifiable to place a child with gastrointestinal symptoms on a gluten-free diet without clearly making a diagnosis of CD?

Pre-test probability of a symptom

e.g. anorexia

73%(62-81)

Decision threshold

PPV of tTGA > 10 x ULN: 0.951 (95% CI:0.922-0.969); LR+ = 21.1 (95%CI: 13.0-34.37).

Conclusion The results of the study raises many questions, the most

important:

• Do we know the natural history of potential CD?• We have to determine which factors most

influence the onset of CD in Mediterranean basin

• Are repeat screenings necessary in NCD group, because CD can present at any age, and if so, at what intervals?

Conclusion The results of the study raises many questions, the most

important:

• In further evaluation we have to clearly identify: - which symptoms can be used to identify

children for screening and diagnostics? - which laboratory data predict the diagnosis of

CD?

Is the PoCT the ideal test?

CD NCD Total

PoCT + 51 3 54

PoCT - 0 54 54

Total 51 57 108

Sens. 100% Spec. 94.7 (88.9-100) LR+ 19 (6.3-57)

Acknowledgment

Stefania Marvaso Giovanni Curro’ Stefano Costa Salvatore Pellegrino Roberto Conti Nibali