Celiac Disease Associated With Nodular Regenerative Hyperplasia, Pulmonary Abnormalities, and IgA Anticardiolipin Antibodies

Abstract

The association of nodular regenerative hyperplasia with celiac disease is not as well established as it is with hepatopulmonary syndrome and portopulmonary hypertension. IgA anticardiolipin antibodies were reported recently in celiac patients with nodular regenerative hyperplasia. The subject of this study was the description of pulmonary abnormalities and IgA anticardiolipin antibodies in celiac patients with noncirrhotic portal hypertension. Five patients with portal hypertension were investigated to diagnose its etiology. Celiac disease was diagnosed by means of autoantibody reactivity and duodenal biopsies. Liver histology revealed nodular regenerative hyperplasia in four patients and suggested its presence in 1 case. Two cyanotic patients had severe hypoxemia with a confirmed diagnosis of hepatopulmonary syndrome. Another case exhibited features of hepatopulmonary syndrome with increased levels of arterial pulmonary pressure. The remaining 2 cases had slight abnormalities of arterial oxygenation. Three patients had reactivity to IgA anticardiolipin antibodies. The concomitance of celiac disease and nodular regenerative hyperplasia, two infrequent conditions, raises suspicion of there being a nonfortuitous coincidence. Pulmonary abnormalities, and especially hepatopulmonary syndrome, are described for the first time in association with celiac disease and nodular regenerative hyperplasia.

Non-cirrhotic Intrahepatic Portal Hypertension: Associated Gut Diseases and Prognostic Factors

“…Association of elevated serum CLPA antibody, celiac disease, and NCIPH is being increasingly recognized [9,15]. Of five NCIPH patients with celiac disease in the current series, celiac disease was recognized after diagnosis of NCIPH in three (Table 3).…”

Prevalence and clinical significance of nodular regenerative hyperplasia in liver biopsies

“…It is thought to be the result of obliterative vasculopathy or to be due to severe and irreversible damage of the sinusoids . NRH has been related to use of certain drugs, including azathioprine and oxaliplatin , and to toxic exposure ; it has been observed in association with a wide variety of systemic diseases, including myelo‐ and lymphoproliferative disorders, autoimmune diseases and HIV infection . Its clinical expression is variable, from asymptomatic to clinical manifestations of PHT .…”

“…NRH has been related to use of certain drugs, including azathioprine and oxaliplatin , and to toxic exposure ; it has been observed in association with a wide variety of systemic diseases, including myelo‐ and lymphoproliferative disorders, autoimmune diseases and HIV infection . Its clinical expression is variable, from asymptomatic to clinical manifestations of PHT . Although NRH was mainly reported and described in the context of symptomatic non‐cirrhotic PHT, an autopsy study by Wanless of 64 cases of NRH among 2500 consecutive autopsies (2.6%), with only one patient presenting PHT diagnosed prior to death, suggests that this pathological condition is often silent and largely underdiagnosed.…”

Hepatobiliary pathology

“…3). The epidemiology, pathology and pathogenesis of nodular regenerative hyperplasia (NRH) were skillfully reviewed [81 ] and one report described NRH in association with celiac disease, IgA anticardiolipid antibodies and pulmonary abnormalities [82 ]. Correlation of molecular and genetic profiles with morphology in liver-cell adenomas enabled subclassification into three main types: those with mutations in hepatocyte nuclear factor 1a, those with b-catenin activation and 'inflammatory' adenomas without mutations [83 ].…”