Celiac disease is an autoimmune disorder primarily targeting the small bowel, although extraintestinal extensions have been reported. The autoimmune processes can affect the liver with manifestations such as primary biliary cirrhosis and autoimmune hepatitis. We describe a 61-year-old woman with celiac disease and an increased levels of aminotransferases. The persistence of increased levels of aminotransferases after 1 year of gluten-free diet and the positivity for an anti-nuclear and anti-double-strand DNA antibodies led to a misdiagnosis of systemic lupus erythematosus-related hepatitis. Based on these findings the patient was placed on steroids, which after a few months were stopped because of the onset of diabetes mellitus. Soon after steroid withdrawal, the patient had a marked increase in aminotransferases and γ-globulins, and a liver biopsy revealed chronic active hepatitis. A course of three months of steroids and azathioprine normalized both biochemical and clinical parameters. Currently the patient is symptom-free and doing well. In conclusion, a hypertransaminasemia persisting after a gluten-free diet should be interpreted as a sign of coexisting autoimmune liver disease. Any autoantibody positivity (in this case to ANA and anti-dsDNA) should be carefully considered in order to avoid misdiagnosis delaying appropriate clinical management.

Celiac disease (CD) is an autoimmune disorder triggered by the ingestion of wheat gliadins and/or other cereal prolamins in patients with genetic predisposition [1]. Although the small bowel is the main target of the disease with a resultant variable degree of malabsorption, growing evidence shows that CD is a systemic disorder that may affect several other organs outside the gut, i.e. the nervous system, thyroid, pancreas, connective tissue, bone, heart, skin, and liver [2]. The occurrence of liver impairment in CD is well established and can be regarded as one of the manifold extraintestinal presentations of gluten-sensitive enteropathy [3]. In this context, different patterns of liver injury can be observed in CD patients, including a close association with autoimmune liver disorders such as primary biliary cirrhosis, autoimmnune hepatitis and primary sclerosing cholangitis [4, 5]. Here we report the case of a CD patient with autoimmune hepatitis (AIH) whose liver involvement was initially attributed to systemic lupus erythematosus (SLE). This misdiagnosis delayed the definition of celiac-related AIH and appropriate management.

A 61-year-old woman was evaluated for an unclear elevation of liver aminotransferases (both AST and ALT about 3 times above the normal limit) associated with a hyper-γ-globulinemia unrelated to hepatotropic viruses and toxic causes. Her past medical history was mainly characterized by two spontaneous miscarriages, iron deficiency anemia, osteopenia and alternating bowel habit. Due to the persistence of gastrointestinal symptoms, she underwent serological tests for CD that resulted positive for anti-endomysial antibodies (IgA EmA, 1:160). Duodenal biopsy revealed severe villous atrophy (3c according to the Marsh-Oberhüber classification). HLA typing revealed DQ2 (DQA1*0501, DQB1*0201) and DQ8 (DQB1*0302) heterodimer positivity. A diagnosis of CD was established and the patient was placed on a gluten-free diet (GFD) with remission of symptoms within about six months. After one year, routine serological tests still revealed an increase in AST and ALT aminotransferases (about 3 times above the normal limit). Other findings included a slight increase in bilirubin (1.5 mg/dl) and low levels of platelets (95,000/mm³). Autoantibody profile was characterized by positive anti-nuclear antibody (ANA +++, homogenous pattern) and anti-double-strand DNA (anti-dsDNA 1:160). A diagnosis of SLE with lupus-related hepatitis was made and steroidal therapy was started (prednisone 25 mg/day). Owing to the onset of steroid-induced diabetes mellitus, prednisone treatment was stopped. Soon after steroid withdrawal, the patient was referred to our unit. Laboratory tests showed a marked increase in AST and ALT aminotransferases (35 times above the normal limit), hyperbilirubinemia 4.05 mg/dl and high levels of total proteins (9.1 g/dl), albumin (3.8 g/dl), γ-globulins (3.6 g/dl), IgG (2,680 mg/dl), IgA (489 mg/dl) and IgM (273 mg/dl). The autoimmune profile confirmed a strong positivity of ANA (+++, with homogenous pattern), anti-smooth muscle antibodies (SMA, ++ with vessel pattern), anti-dsDNA (1:320), while CD-related autoantibodies were negative, showing a good compliance to GFD. Ultrasound-Doppler examination revealed an enlarged liver with irregular borders and coarse echo pattern along with signs of portal hypertension. A liver biopsy showed chronic active hepatitis with piecemeal necrosis and lympho-plasmacellular periportal infiltrate (fig. ​fig.11). A diagnosis of AIH associated with CD was made and the patient was treated with methylprednisolone (16 mg/day) and azathioprine (2 mg/kg = 100 mg/day). At 18-month follow-up, the patient was doing well with an almost complete normalization of aminotransferases (fig. ​fig.22), γ-globulins (fig. ​fig.33) and bilirubin. Methylprednisolone and azathioprine have been tapered down to the current dose of 4 mg/day and 50 mg/day, respectively. The patient gave her informed consent to the publication of this case report.

The authors declare no conflict of interest.