Serum immunoglobulin A concentration is a reliable biomarker for liver fibrosis in non-alcoholic fatty liver disease

World J Gastroenterol. 2014 Sep 21;20(35):12566-73. doi: 10.3748/wjg.v20.i35.12566.

Abstract

Aim: To evaluate the diagnostic accuracy of serum Immunoglobulin A (IgA) for differentiating early stage nonalcoholic fatty liver disease (NAFLD) from nonalcoholic steatohepatitis (NASH).

Methods: All cases had fatty liver change confirmed by ultrasound and aminotransferases of at least twice the normal level. Clinical and biochemical data, including serum IgA, were obtained from 50 histologically proven NAFLD cases and 54 healthy controls. Fasting whole blood samples were obtained from the study population. Immunoturbidimetric methods were used to measure the IgA levels. All NAFLD cases were hospitalized for liver biopsy. Liver specimens were examined for steatosis, steatohepatitis and fibrosis within hepatocytes. Patients were categorized into two groups: NASH and non-NASH. Variables were compared within cases (NASH vs non-NASH) and controls. Cut-off values of serum IgA were evaluated using analysis of receiver operating characteristic (ROC curves). Associations between the variables were tested using calculations of correlation coefficients. Statistical significances were assigned to P values < 0.05.

Results: The extent of liver fibrosis correlated positively with IgA levels. Subjects with no fibrosis in their liver biopsies had a lower IgA level (301.5 ± 91.2 mg/dL) than subjects with any degree of fibrosis (388.8 ± 140.8 mg/dL), (P = 0.01). IgA levels were higher in NASH cases, and its value was significantly higher for higher degrees of fibrosis. Patients with perisinusoidal or pericellular fibrosis had significantly higher levels of IgA (403.5 ± 133.9 mg/dL, 418.2 ± 129.5 mg/dL) compared to those without it (301.8 ± 94.9 mg/dL, 297.7 ± 91.5 mg/dL), respectively. No significant correlation was found between steatosis grade and serum IgA levels. Based on ROC analysis, the best predictive IgA cutoff value for detecting liver fibrosis was 360 mg/dL (61% sensitivity, 81% specificity).

Conclusion: The serum IgA level is useful to evaluate the severity of liver fibrosis and can be used serially for evaluation and follow-up of NAFLD cases.

Keywords: Biological Markers; Fibrosis; Immunoglobulin A; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Area Under Curve
  • Biomarkers / blood
  • Biopsy
  • Case-Control Studies
  • Disease Progression
  • Female
  • Humans
  • Immunoglobulin A / blood*
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / etiology*
  • Liver Cirrhosis / immunology
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease / blood
  • Non-alcoholic Fatty Liver Disease / complications*
  • Non-alcoholic Fatty Liver Disease / diagnosis
  • Non-alcoholic Fatty Liver Disease / immunology
  • Predictive Value of Tests
  • Prognosis
  • ROC Curve
  • Reproducibility of Results
  • Serologic Tests
  • Severity of Illness Index
  • Up-Regulation

Substances

  • Biomarkers
  • Immunoglobulin A