Increased Risk of Nonalcoholic Fatty Liver Disease in Patients With Coeliac Disease on a Gluten-free Diet

Beyond Traditional Metabolic Factors

F. Tovoli; G. Negrini; R. Farì; E. Guidetti; C. Faggiano; L. Napoli; L. Bolondi; A. Granito


Aliment Pharmacol Ther. 2018;48(5):538-546. 

In This Article

Abstract and Introduction


Background: A gluten-free diet (GFD) is known to be associated with altered macronutrient intake and metabolic syndrome. Nonalcoholic fatty liver disease (NAFLD) is the hepatic hallmark of metabolic syndrome. The risk of NAFLD in patients with coeliac disease (CD) adhering to a GFD remains to be fully investigated; in particular, data from real-life clinical settings are lacking.

Aim: To assess the prevalence and relative risk of NAFLD in CD patients treated with a GFD.

Methods: Case-control study, with prospective enrolment of CD outpatients following a GFD and controls. Patients were matched for demographic characteristics (age and gender) and metabolic risk factors (overweight, diabetes mellitus, total cholesterol, and triglycerides) using a 1:1 ratio. NAFLD was diagnosed according to the European Association for the Study of the Liver criteria.

Results: 202 CD patients and 202 controls were compared. The raw prevalence of NAFLD was 34.7% and 21.8% in the CD and control group, respectively (P = 0.006). Binary logistic regression confirmed an increased risk of NAFLD in the CD group (adjusted odds ratio = 2.90, 95% confidence interval: 1.64–5.15, P < 0.001). Additionally, the relative risk for NAFLD was notably higher in non-overweight CD patients (adjusted odds ratio = 5.71, 95% confidence interval: 2.30–14.19, P < 0.001).

Conclusions: More than one-third of CD patients adhering to a GFD had concurrent NAFLD, accounting for a three-fold increased risk compared to the general population. Dietary advice provided using a patient-tailored approach should assist CD patients with NAFLD in achieving an appropriate nutritional intake whilst reducing the risk of long-term liver-related events.


Patients with coeliac disease (CD) have to follow a lifelong gluten-free diet (GFD). This diet is safe and can reduce the long-term risk of serious complications, both neoplastic and non-neoplastic.[1] A GFD is related to increased lipid[2–6] and carbohydrate[2,7–9] intake. Moreover, many adults and children with CD become overweight after treatment.[10–13] Recent evidence also shows that a GFD can worsen glucose tolerance and induce metabolic syndrome in a proportion of CD patients,[14] potentially increasing their cardiovascular risk.[15,16]

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome, and is related to an increased risk of liver cirrhosis and primary liver cancer.[17] Historically, liver steatosis has been reported to be a possible manifestation of CD in patients still on a gluten-containing diet.[18] Additionally, about 3% of patients diagnosed with NAFLD actually have an underlying CD.[19,20]

Data on the development of a fatty liver whilst following a GFD are still emerging. In a Swedish registry study, Reilly et al[21] described an increased risk of NAFLD in CD patients treated with a GFD, with a hazard ratio of 2.8 (95% CI: 2.0–3.8). Cohort studies and evaluations in geographically different populations are missing, leaving uncertainties about the actual prevalence of NAFLD in the CD population, and the potential influence of local nutritional factors in determining the relative risk.