Metabolic-associated Fatty Liver Disease (MAFLD) in Celiac Disease

Antonio Rispo; Nicola Imperatore; Maria Guarino; Raffaella Tortora; Anna Alisi; Valentina Cossiga; Anna Testa; Simona Ricciolino; Andrea Fiorentino; Filomena Morisco

Disclosures

Liver International. 2021;41(4):788-798. 

In This Article

Abstract and Introduction

Abstract

Background and Aims: Coeliac disease (CD) is considered a high-risk condition for developing non-alcoholic fatty liver disease (NAFLD) and other related metabolic disorders, particularly after commencing gluten-free diet (GFD). Recently, a new concept of metabolic-associated fatty liver disease (MAFLD) has been proposed to overcome the limitations of NAFLD definition. This study aimed at exploring the prevalence of NAFLD and MAFLD in CD patients at the time of CD diagnosis and after 2 years of GFD. Furthermore, we evaluated the role of PNPLA3 rs738409 in the development of NAFLD and MAFLD in the same population.

Methods: We retrospectively enrolled all newly diagnosed CD patients who underwent clinical, laboratory and ultrasonography investigations both at diagnosis and after 2 years of follow-up. Moreover, a PNPLA3 rs738409 genotyping assay was performed.

Results: Of 221 newly diagnosed CD patients, 65 (29.4%) presented NAFLD at CD diagnosis, while 32 (14.5%) met the criteria for MAFLD (k = 0.57). There were no significant differences between NAFLD and MAFLD, except for the higher rate of insulin resistance (IR) of MAFLD patients (75% vs 33.8%, P < .001). At 2 years of follow-up, 46.6% of patients developed NAFLD while 32.6% had MAFLD (k = 0.71). MAFLD subjects had higher transaminases (P = .03), LDL-cholesterol (P = .04), BMI and waist circumference and higher IR than NAFLD patients. MAFLD patients showed higher non-invasive liver fibrosis scores than NAFLD subjects (APRI = 1.43 ± 0.56 vs 0.91 ± 0.62, P < .001; NFS=−1.72 ± 1.31 vs −2.18 ± 1.41, P = .03; FIB-4 = 1.27 ± 0.77 vs 1.04 ± 0.74, P = .04). About PNPLA3 polymorphisms, at 2 years follow-up, NAFLD subjects presented a higher rate of heterozygosis (40.8%) and homozygosis (18.4%) polymorphisms than non-NAFLD (26.3% and 7.6%, respectively, P = .03 and 0.02), while no correlation between PNPLA3 polymorphisms and MAFLD was seen.

Conclusions: The new MAFLD definition better reflects the metabolic alterations following GFD in CD population. This new classification could be able to identify patients at higher risk of worse metabolic outcome, who need a close multidisciplinary approach for their multisystemic disease.

Introduction

Coeliac disease (CD) is the most common immune-mediated enteropathy in Western countries, triggered by the exposure to gluten in genetically susceptible subjects.[1] Recent studies indicated that weight variations are usual in patients suffering from CD after starting a gluten-free diet (GFD)[2,3] and these modifications can lead to the subsequent development of hepatic steatosis (HS), diabetes mellitus, hypertension, dyslipidaemia and metabolic syndrome (MS).[4]

Non-alcoholic fatty liver disease (NAFLD) has been recognized as the hepatic manifestation of the MS[1] and constitutes the most frequent liver pathologic condition worldwide.[5]

A recent study by our team reported a prevalence of MS of 29% in CD patients on a GFD regimen for 1 year; moreover, 65% of patients with MS also presented HS.[6]

On the other hand, in addition to GFD, CD patients have various other risk factors to develop NAFLD such as increased gut permeability, malabsorption and alteration of gut microbiota, suggesting that the presence of NAFLD in this group of patients may have a different origin and pathogenesis.[7–15]

Considering the strict association between NAFLD and other metabolic disorders, an international consensus in 2020 has proposed a new concept for the diagnosis of metabolic-associated fatty liver disease (MAFLD).[16] The diagnostic criteria for MAFLD are significantly different from that previously utilized for NAFLD.[17–19] The two most important differences are (a) the presence of metabolic abnormalities is necessary for the diagnosis of MAFLD,[20] and (b) MAFLD definition does not require the exclusion of liver diseases of other aetiology[19] but the recognition in MAFLD as the most relevant driver of the disease.

As a consequence, the application of this concept modifies the diagnosis of NAFLD from an exclusion to an inclusion process.

Starting from these considerations, we aimed at exploring the prevalence of NAFLD and MAFLD in CD patients at the time of CD diagnosis and after 2 years of GFD. Furthermore, we evaluated the role of PNPLA3 rs738409 in the development of NAFLD and MAFLD in the same population.

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