The results of follow-up intestinal biopsies in patients with celiac disease may be useful in evaluating their risk of developing lymphoproliferative malignancies, according to a study that involved more than 7,000 patients in Sweden with celiac disease.
Patients with celiac disease are at an increased risk for lymphoproliferative malignancy (LPM), but the risk was "most pronounced" among those patients whose follow-up biopsy results, obtained after the diagnostic biopsy, had persistent villous atrophy, judging from the study findings. The risk was "less pronounced among those with mucosal healing," reported Dr. Benjamin Lebwohl of the Celiac Disease Center at Columbia University, New York, and his coauthors.
The reason for the increased risk of LPM among patients with celiac disease is not known. These results indicate that the increased risk for LPM "may be affected by mucosal healing," the researchers concluded. The study appears online in Annals of Internal Medicine.
The researchers compared the rates of LPM among 7,625 patients with biopsy-confirmed celiac disease (confirmed by the presence of villous atrophy on the biopsy) and follow-up biopsy to document healing at a median of 1.3 years later. The patients’ median age at the time of diagnosis was 35 years and 63% were female; they were followed for a median of almost 11 years after they were diagnosed and a median of almost 9 years after the follow-up biopsy
Of the total, 53 patients (0.7%) developed LPM a median of 4.9 years after the follow-up biopsy. Persistent villous atrophy was identified in 43% of the follow-up biopsies.
The risk of LPM among those with persistent villous atrophy on the follow-up biopsy was more than twofold greater than the risk among those with biopsies that showed mucosal healing (hazard ratio, 2.26), overall. But during the first year after the follow-up biopsy, the risk of LPM among those with persistent villous atrophy was almost fourfold greater than the risk among those with mucosal healing (HR, 3.67), diminishing over time. The risk was almost twofold higher (HR, 1.99), 1-5 years after the follow-up biopsy and more than 5 years after the biopsy, but was not statically significant.
"It is premature to conclude that the degree of dietary adherence affects LPM risk," the authors said.
Both men and women showed an association between a greater LPM risk and persistent villous atrophy, and the risk was higher among those who were aged older than 60 years at the time of the follow-up biopsy. Those with persistent villous atrophy had a greater risk of developing LPM than that of the general population.
The authors said they were not aware of any study that estimated the hazard ratios for LPM based on the histopathologic results of follow-up biopsies in patients with celiac disease.
One of the limitations of the study was the lack of information on how well patients followed the gluten-free diet, so "it is premature to conclude that the degree of dietary adherence affects LPM risk," the authors said. But their results "should prompt further evaluation of mucosal healing as a goal for patients with celiac disease to reduce their risk for LPM," they concluded.
Patients who not comply with a gluten-free diet are more likely to have persistent villous atrophy, they noted.
Dr. Lebwohl disclosed ties with the National Institutes of Health, the American Scandinavian Foundation, and the Celiac Sprue Association, which funded the study along with Oresbro University Hospital, Karolinska Institutet, the Swedish Society of Medicine, Swedish Research Council, and Swedish Celiac Society. Dr Joseph Murray, a coauthor, received grants from the NIH.
*This story was updated 8/8/2013
