Elsevier

The Lancet

Volume 352, Issue 9121, 4 July 1998, Pages 26-29
The Lancet

Early Report
Coeliac disease hidden by cryptogenic hypertransaminasaemia

https://doi.org/10.1016/S0140-6736(97)11222-3Get rights and content

Summary

Background

Hypertransaminasaemia of unknown, cryptogenic, origin occasionally has been found to be the only sign of coeliac disease. Raised concentrations of transaminases, or aminotransferases, have been retrospectively observed in about a half of patients with coeliac disease who are on a gluten-containing diet. We aimed to establish the overall prevalence of coeliac disease among patients with cryptogenic hypertransaminasaemia.

Methods

Of the 600 consecutive patients referred to our outpatient clinic for liver disease due to raised serum transaminases from September, 1995, to June, 1997, 55 were classified as having cryptogenic hypertransaminasaemia after the exclusion of every known cause of liver disease. These patients were tested by indirect immunofluorescence for IgA to endomysium and for IgA and IgG to gliadin.

Findings

Five patients were positive for both IgA to endomysium and IgG to gliadin, whereas IgA to gliadin was only found in four patients. IgG to gliadin was also present in another patient who was not positive for antibodies to endomysium. The six antibody-positive patients had duodenal biopsy that showed a subtotal villous atrophy consistent with coeliac disease in the five patients with antibodies to endomysium. The patient with only IgG to gliadin had a normal small-intestine mucosa. None of the five patients with coeliac disease had gastrointestinal symptoms. Liver biopsy samples were taken from three of the five patients with flat mucosa and showed a histological picture of nonspecific reactive hepatitis. Transaminase concentrations reverted to normal within 6 months in four patients with coeliac disease who followed a strict gluten-free diet.

Interpretation

Our results show that about 9% of patients with cryptogenic hypertransaminasaemia are affected by symptom-free coeliac disease. Gluten-sensitive enter-opathy and antibody screening for coeliac disease by means of antibodies to endomysium and gliadin should be considered in these patients.

Introduction

Retrospective studies have shown that many patients with untreated coeliac disease show liver involvement characterised by elevated concentrations of serum transaminase, or aminotransferase, and a liver histology consistent with a nonspecific reactive hepatitis.1, 2, 3 In these patients liver damage was proved to be gluten-dependent, as confirmed by disappearance of histological and biochemical signs of the hepatic lesions after following a strict gluten-free diet for a few months.4 Also, hypertransaminasaemia of unknown, cryptogenic, origin has occasionally been reported in childhood as an early biochemical sign of coeliac disease free of gastrointestinal symptoms.4, 5 The finding of unexplained raised serum transaminase concentrations is not as rare as originally thought. Because diagnostic tests for coeliac disease are not included among investigations for cryptogenic hypertransaminasaemia at present, some cases of coeliac disease may therefore go unrecognised. Early identification of gluten-sensitive enteropathy is important because strict adherence to a gluten-free diet can prevent neoplastic and systemic complications and improve symptoms of associated diseases.6, 7, 8, 9, 10 These assumptions have prompted us to investigate coeliac disease in a series of patients with cryptogenic hypertransaminasaemia, to establish how many of them have coeliac disease, and so to find out whether an unexplained increase in serum transaminases can be considered a high-risk condition for gluten-sensitive enteropathy.

Section snippets

Patients

600 consecutive adult patients were referred to the outpatient liver clinic of S Orsola Policlinic between September, 1995, and June, 1997, because of raised serum transaminases. Nearly all of them were symptom-free (a few patients found they were easily fatigued) and had become aware of their hypertransaminasaemia as a consequence of routine blood tests. 55 (9%) of them were classified as having cryptogenic hypertransaminasaemia after the exclusion of every known cause of liver disease.

Viral

Results

Five (9%) of the 55 patients with cryptogenic hypertransaminasaemia were positive for both IgG to gliadin and IgA to endomysium, whereas IgA to gliadin was found in only four of these patients. IgG to gliadin was also present in another patient who was not positive for antibodies to endomysium. Antibody titre ranged from one in 40 to one in 320 for antibodies to endomysium and from one in ten to one in 160 for antibodies to gliadin. For the six patients who were positive for antibodies,

Discussion

The clinical presentation of gluten-sensitive enteropathy can be deceptive, varying tremendously from patient to patient, and appears to depend on the length of small intestine damaged.16 Whereas the typical symptoms of diarrhoea, flatulence, weight loss, and fatigue (overt malabsorption syndrome) are frequently found in people with coeliac disease, diffuse small-bowel involvement, atypical, single-symptom, or even symptom-free forms of the disease are associated with a mucosal lesion limited

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