title: Serum immunoglobulin A concentration is a reliable biomarker for liver fibrosis in non-alcoholic fatty liver disease.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Iradj Maleki, Mahmood Reza Aminafshari, Tarang Taghvaei, Vahid Hosseini, Elahe Orang, Inflammatory Diseases of Upper Gastrointestinal Tract Research Center, Mazandaran University of Medical Sciences, Sari 48166-33131, Iran.
authors.forename: Iradj
authors.initials: I
authors.lastname: Maleki
authors.affiliation: Iradj Maleki, Mahmood Reza Aminafshari, Tarang Taghvaei, Vahid Hosseini, Elahe Orang, Inflammatory Diseases of Upper Gastrointestinal Tract Research Center, Mazandaran University of Medical Sciences, Sari 48166-33131, Iran.
authors.forename: Mahmood Reza
authors.initials: MR
authors.lastname: Aminafshari
authors.affiliation: Iradj Maleki, Mahmood Reza Aminafshari, Tarang Taghvaei, Vahid Hosseini, Elahe Orang, Inflammatory Diseases of Upper Gastrointestinal Tract Research Center, Mazandaran University of Medical Sciences, Sari 48166-33131, Iran.
authors.forename: Tarang
authors.initials: T
authors.lastname: Taghvaei
authors.affiliation: Iradj Maleki, Mahmood Reza Aminafshari, Tarang Taghvaei, Vahid Hosseini, Elahe Orang, Inflammatory Diseases of Upper Gastrointestinal Tract Research Center, Mazandaran University of Medical Sciences, Sari 48166-33131, Iran.
authors.forename: Vahid
authors.initials: V
authors.lastname: Hosseini
authors.affiliation: Iradj Maleki, Mahmood Reza Aminafshari, Tarang Taghvaei, Vahid Hosseini, Elahe Orang, Inflammatory Diseases of Upper Gastrointestinal Tract Research Center, Mazandaran University of Medical Sciences, Sari 48166-33131, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Rafiei
authors.affiliation: Iradj Maleki, Mahmood Reza Aminafshari, Tarang Taghvaei, Vahid Hosseini, Elahe Orang, Inflammatory Diseases of Upper Gastrointestinal Tract Research Center, Mazandaran University of Medical Sciences, Sari 48166-33131, Iran.
authors.forename: Zhila
authors.initials: Z
authors.lastname: Torabizadeh
authors.affiliation: Iradj Maleki, Mahmood Reza Aminafshari, Tarang Taghvaei, Vahid Hosseini, Elahe Orang, Inflammatory Diseases of Upper Gastrointestinal Tract Research Center, Mazandaran University of Medical Sciences, Sari 48166-33131, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Barzin
authors.affiliation: Iradj Maleki, Mahmood Reza Aminafshari, Tarang Taghvaei, Vahid Hosseini, Elahe Orang, Inflammatory Diseases of Upper Gastrointestinal Tract Research Center, Mazandaran University of Medical Sciences, Sari 48166-33131, Iran.
authors.forename: Elahe
authors.initials: E
authors.lastname: Orang
mesh_terms: D000328:Adult; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood*; D008103:Liver Cirrhosis / Q000097:blood / Q000175:diagnosis / Q000209:etiology* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000150:complications* / Q000175:diagnosis / Q000276:immunology; D011237:Predictive Value of Tests; D011379:Prognosis; D012372:ROC Curve; D015203:Reproducibility of Results; D012698:Serologic Tests; D012720:Severity of Illness Index; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D007070:Immunoglobulin A
keywords: Biological Markers; Fibrosis; Immunoglobulin A; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease