Celiac Disease and Primary Biliary Cirrhosis: An Immune Link

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Celiac Disease and Primary Biliary Cirrhosis: An Immune Link

Association Between PBC & CD: Literature Review


A close association between CD and PBC has been extensively reported in the literature. Of note, the risk of finding CD in PBC patients seems to be higher than that of PBC detection in CD subjects (Table 1). A 12-year study of a stable population of 250,000 people in south Wales found a 3% prevalence of PBC in 143 patients with CD and 6% prevalence of CD in 67 patients with PBC. Two national cohort studies performed in Denmark and Sweden detected a very low prevalence of PBC (~0.3%) in large series of CD patients. A very elevated CD prevalence (7%) was detected in 57 PBC Irish patients, who did not complain of gastrointestinal symptoms. A great geographical variability of CD finding in PBC patients was confirmed by two other studies; one from Canada, showing a CD prevalence of 2.6% in 378 PBC patients, and another collaborative study from Italy and Spain, reporting CD in seven (4%) out of 173 PBC patients. In these seven PBC patients, CD diagnosis was confirmed by IgA EmA positivity and severe small intestinal mucosa damage (lesion type from 3a to 3c, according to Marsh–Oberhüber classification). All patients were middle-aged females (median age: 55 years; range: 43–70), and all but two did not complain of clinical signs suggestive for CD. One of the two symptomatic patients showed a typical malabsorption syndrome characterized by diarrhea, weight loss, hypocalcemia and iron-deficiency anemia. In the other patient, the existence of CD could be suspected again due to iron-deficiency anemia and Hashimoto thyroiditis, an autoimmune condition closely related to both PBC and CD. Of the seven PBC patients found to be celiacs, two had already developed a histological picture of severe liver cirrhosis (stage IV) when CD was discovered, whereas the other five showed mild liver damage (stage I–II) when GFD was added to biliary acid treatment. In the two patients with severe cirrhosis, gluten restriction did not change the clinical course of liver disease, characterized by pruritus and jaundice, and did not improve the biochemical picture of cholestasis with persistence of hyperbilirubinemia and raised levels of alkaline phoshatase. In their follow-up, both had a progressive liver failure causing death in one of them, whereas the other underwent an OLT with a good outcome. On the contrary, the addition of GFD to ursodeoxycholic treatment slowed down the progression of liver disease in the other five patients without cholestasis and with mild liver impairment, which has remained stable after a follow-up at 10 years. Gluten withdrawal induced the normalization of intestinal absorptive function with disappearance of diarrhea and resolution of iron-deficiency anemia in the two PBC patients symptomatic for CD. A 6–12-month period of GFD determined the disappearance of EmA, which remained negative in the follow-up, together with the other CD-related antibodies, that is, tTGA and DGP, but did not change the titer of AMA.

Although tTGA of IgA class proved to be the most sensitive test for CD in PBC patients, as well as in the general population, and in other at risk patients for CD, these antibodies have displayed a particularly low specificity for CD in PBC patients. Bizzaro et al. found that tTGA showed the highest rate of false-positives (10.4%) in PBC patients in comparison with connective tissue disorders and inflammatory bowel disease patients. In a further article, the same authors reported that only two out of 28 PBC cases positive for tTGA of IgA class were diagnosed as celiacs. On the basis of these findings, the diagnostic accuracy of tTGA, particularly when positive at a low titer, in PBC patients should be confirmed by EmA, which also remains the most specific test for CD in thisclinical setting.

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