Serum Immunoglobulin Levels Predict Fibrosis in Patients With Non-Alcoholic Fatty Liver Disease

J Hepatol. 2014 May;60(5):1055-62. doi: 10.1016/j.jhep.2014.01.010. Epub 2014 Jan 18.


Background & aims: A third of the population are estimated to have NAFLD of varying severity. Serum immunoglobulins are frequently elevated in patients with chronic liver disease, but little is known about serum immunoglobulin levels in patients with NAFLD. Aim of this study was to evaluate serum immunoglobulin levels (IgA, IgG, and IgM) in a large cohort of patients with biopsy-proven NAFLD and determine if immunoglobulin levels are associated with clinical or histological features.

Methods: Patients seen in a tertiary fatty liver clinic between 1999 and 2009 were included. Liver biopsies were assessed using the Kleiner score. Immunoglobulin levels and other blood tests were taken at time of biopsy.

Results: 285 patients (110 simple steatosis and 175 NASH) had serum immunoglobulins measured within 6months of liver biopsy. 130 (46%) patients had elevated (>1× upper limit of normal) serum IgA levels, 28 (10%) patients had elevated IgG and 22 (8%) raised IgM. Serum IgA levels were elevated more frequently in patients with NASH compared with subjects with simple steatosis (55% vs. 31%, p<0.001). Overall, 55 (19%) patients had advanced liver fibrosis (Kleiner stage 3-4). There was a significant positive association between serum IgA levels and the stage of fibrosis (p<0.001). Serum IgA, age, platelets, AST/ALT ratio and BMI were all independently with advanced fibrosis following multivariate analysis. A model constructed from these independent predictors accurately predicted advanced fibrosis (AUROC 0.87).

Conclusions: The serum IgA level was frequently elevated in patients with NAFLD and was an independent predictor of advanced fibrosis.

Keywords: Diabetes; Fatty liver; Fibrosis; IgA; IgG; Immunoglobulins; NASH; Steatohepatitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cohort Studies
  • Diabetes Complications / immunology
  • Diabetes Complications / pathology
  • Disease Progression
  • Female
  • Humans
  • Immunoglobulin A / blood
  • Immunoglobulin G / blood
  • Immunoglobulin M / blood
  • Immunoglobulins / blood*
  • Liver / pathology
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / immunology
  • Liver Cirrhosis / pathology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Non-alcoholic Fatty Liver Disease / complications
  • Non-alcoholic Fatty Liver Disease / immunology*
  • Non-alcoholic Fatty Liver Disease / pathology*
  • Predictive Value of Tests
  • Risk Factors


  • Immunoglobulin A
  • Immunoglobulin G
  • Immunoglobulin M
  • Immunoglobulins