The spectrum of liver abnormalities in the context of CD is particularly wide, however, two main forms of liver damage, i.e. cryptogenic and autoimmune, appear to be strictly associated with gluten-sensitive enteropathy [3
]. Hypertransaminasemia has been reported in up to 47% of adults with a classical presentation of CD at the time of diagnosis [6
]. Conversely, CD is present in about 9% of patients with chronic unexplained hypertransaminasemia and liver blood test abnormalities may also be the sole presentation of atypical CD [7
]. In patients with untreated CD, cryptogenic liver disorder, also referred to as ‘celiac hepatitis’, is usually characterized by a mild increase in aminotransferase levels with normal values of bilirubin and γ-GT [8
]. A GFD leads to normalization of serum aminotransferases in almost all patients with CD within one year of good adherence to the diet [10
]. In patients with missed or late diagnosis, CD may be also associated with severe forms of liver disease, including advanced cirrhosis which can require liver transplantation [11
]. Sometimes the identification of CD in these patients can significantly improve liver function, leading to disappearance of ascites and jaundice, thereby avoiding liver transplantation [12
Another clinically relevant association, which pertains to the present case report, is that between CD and autoimmune liver disorders. In this context, primary biliary cirrhosis is the most frequent liver disease found in patients with CD [13
]. In this case report, we describe the association between CD and type 1 AIH. Such an association has been demonstrated by two antibody screening studies for CD in large series of patients with AIH [4
]. One of these studies included the largest series of patients with AIH screened for CD with serology [4
]. Based on serological response, the CD prevalence was 4.4% (8.3% in type 2 AIH, 3.8% in type 1 AIH), whereas, taking into account only cases who underwent duodenal biopsy, CD prevalence was 2.8%.
In the patient described here, GFD improved the symptoms attributable to CD due to normalization of the small intestinal mucosa, but it did not normalize aminotransferases. This finding along with the positivity for ANA (homogeneous pattern) and anti-dsDNA antibodies led to a misdiagnosis of SLE-related hepatitis. Based on the lack of clinical signs and symptoms suggesting SLE, the presence of these two autoantibodies should have been considered a clue to type 1 AIH [15
] whose diagnosis could be supported by the detection of high-titer circulating SMA (vessel pattern). In addition, another relevant clinical feature of our patient suggesting type 1 AIH was the rebound of aminotransferase levels after steroid withdrawal. Finally, the histological pattern was consistent with AIH, showing chronic active hepatitis with piecemeal necrosis.
The present case was a diagnostic challenge as it dealt with the interesting and not uncommon association between CD and liver disease. Accordingly, we propose the following conclusions: (a) Hypertransaminasemia can be secondary to CD-related hepatitis; it can as well be a clue for underlying coexisting autoimmune liver disease. For these reasons liver enzyme levels should be checked routinely in all patients with CD at diagnosis. (b) Once it has been established that hypertransaminasemia is of CD origin, liver enzymes should be controlled after 6-12 months after the beginning of a GFD. Persistently elevated levels of aminotransferases (once a poor compliance to the diet has been excluded) should be regarded as a sign of coexisting autoimmune liver disease other than celiac hepatitis, thus the etiology of liver disorder must be re-assessed. (c) The positivity of ANA and anti-dsDNA antibodies should not be regarded as uniquely diagnostic for SLE, but these autoantibodies along with SMA suggest an underlying type 1 AIH, particularly in the presence of very high levels of aminotransferases and γ-globulin.
This case helps to shed light on the appropriateness and accurate interpretation of laboratory and diagnostic tests to establish a diagnosis of CD-related liver disease.