Serum immunoglobulin levels predict fibrosis in patients with non-alcoholic fatty liver disease.
OBJECTIVE
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.
Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital, Newcastle Upon Tyne, United Kingdom; Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, United Kingdom. Electronic address: stuart.mcpherson@nuth.nhs.uk.
Stuart
S
McPherson
Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital, Newcastle Upon Tyne, United Kingdom.
Elsbeth
E
Henderson
Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, United Kingdom; The School of Medicine, University of Adelaide, Australia.
Alastair D
AD
Burt
Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital, Newcastle Upon Tyne, United Kingdom; Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, United Kingdom.
Christopher P
CP
Day
Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital, Newcastle Upon Tyne, United Kingdom; Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, United Kingdom.
Quentin M
QM
Anstee
D000328:Adult; D015331:Cohort Studies; D048909:Diabetes Complications / Q000276:immunology / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007136:Immunoglobulins / Q000097:blood*; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000150:complications / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications / Q000276:immunology* / Q000473:pathology*; D011237:Predictive Value of Tests; D012307:Risk Factors
D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins
Diabetes; Fatty liver; Fibrosis; IgA; IgG; Immunoglobulins; NASH; Steatohepatitis