Serum immunoglobulin A levels and non-alcoholic fatty liver disease

Background: Intestinal immunity, and immunoglobulin A (IgA) in particular, may play an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). The aim of this study was to document the prevalence of elevated serum IgA levels in NAFLD patients and determine whether the severity and course of NAFLD differs in those with elevated (E-IgA) versus normal (N-IgA) levels. Methods: A retrospective review of a clinical database containing demographic, laboratory, and histologic findings of adult NAFLD patients was undertaken. Liver biochemistry, model for end stage-liver disease (MELD) and Fib-4 scores served to document disease severity and progression. Results: Of 941 NAFLD study subjects, 254 (27%) had E-IgA at presentation. E-IgA patients were older, and had lower serum albumin levels and higher MELD scores than N-IgA patients. The percent of E-IgA patients with Fib-4 scores >3.25 (suggestive of cirrhosis) was also higher (25% vs. 5.5%, p<0.001). E-IgA patients had higher METIVIR fibrosis scores (2.2 +/- 1.4 vs. 1.0 +/- 1.2, p<0.0001) than N-IgA patients. After mean follow-ups of 47 (E-IgA) and 41 (N-IgA) months, serum albumin levels remained lower, INR values were now more prolonged and MELD scores higher in E-IgA patients. Of the non-cirrhotic patients at baseline, a larger percent of E-IgA patients developed cirrhosis by Fib-4 testing at last visit (11% vs. 2.9%, p<0.001). Conclusions: Elevated serum IgA levels are common in NAFLD patients and when present, are associated with more advanced disease. Patients with elevated serum IgA levels are also more likely to progress to cirrhosis than those with normal levels.