Case Control Study
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World J Gastroenterol. Sep 21, 2014; 20(35): 12566-12573
Published online Sep 21, 2014. doi: 10.3748/wjg.v20.i35.12566
Serum immunoglobulin A concentration is a reliable biomarker for liver fibrosis in non-alcoholic fatty liver disease
Iradj Maleki, Mahmood Reza Aminafshari, Tarang Taghvaei, Vahid Hosseini, Alireza Rafiei, Zhila Torabizadeh, Maryam Barzin, Elahe Orang
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
Alireza Rafiei, Department of Immunology, Mazandaran University of Medical Sciences, faculty of Medicine, Sari 48166-33131, Iran
Zhila Torabizadeh, Department of Pathology, Mazandaran University of Medical Sciences, Imam Khomeini Hospital, Sari 48166-33131, Iran
Maryam Barzin, Department of Radiology, Mazandaran University of Medical Sciences, Imam Khomeini Hospital, Sari 48166-33131, Iran
Author contributions: Maleki I was involved in the design of the study, patient selection, supervision, statistical analysis, writing the manuscript and its revision; Aminafshari MR was involved in the design of the study, patient selection and supervision; Taghvaei T was involved in the design of the study, patient selection and writing the manuscript; Hosseini V was involved in the design of the study and patient selection; Rafiei A was involved in the design of the study and performance of the laboratory examinations; Torabizadeh Z was mainly involved in the study design and performance of the laboratory examinations; Barzin M was involved in the study design, and the ultrasound and imaging studies of the patients; Orang E was involved in the preparation of the study proposal and the manuscript.
Supported by Mazandaran University of Medical Sciences
Correspondence to: Zhila Torabizadeh, MD, Assistant Professor of Pathology, Department of Pathology, Mazandaran University of Medical Sciences, Imam Khomeini Hospital, Amir Mazandarani Street, Sari 48166-33131, Iran. zhtorabi@yahoo.com
Telephone: +98-911-1513073 Fax: +98-151-3218086
Received: January 26, 2014
Revised: April 20, 2014
Accepted: June 20, 2014
Published online: September 21, 2014
Processing time: 236 Days and 0.8 Hours
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: Non-alcoholic Fatty Liver Disease; Biological Markers; Immunoglobulin A; Liver Cirrhosis; Fibrosis

Core tip: Nonalcoholic steatohepatitis (NASH) is a severe subtype of Nonalcoholic Fatty Liver Disease (NAFLD) that can progress to advanced liver disease and hepatocellular carcinoma. In this study, we investigated the diagnostic accuracy of serum Immunoglobulin A (IgA) as a biomarker for differentiating early stage NAFLD from NASH. We found that the extent of liver fibrosis correlated positively with IgA levels and these were higher in NASH cases than in non-NASH cases. Based on receiver operating characteristic analysis, the best predictive IgA cutoff value for detecting liver fibrosis was 360 mg/dL (61% sensitivity, 81% specificity).