Original Article
Clinical
Liver Fatty Acid-binding Protein Is A Diagnostic Marker to Detect Liver Injury Due to Chronic Hepatitis C Infection

https://doi.org/10.1016/j.arcmed.2012.11.007Get rights and content

Background and Aims

Liver fatty acid-binding protein (L-FABP) is a small molecule. The aim of this study was to examine L-FABP levels and to detect its diagnostic value in chronic hepatitis C (CHC).

Methods

We studied 22 patients with CHC and 20 healthy control subjects. Patients with persistently elevated serum aminotransferases and positive HCV RNA were included in the study. Patients with CHC underwent percutaneous liver biopsy. Serum level of L-FABP was determined by ELISA method.

Results

Patients with CHC had significantly increased levels of L-FABP compared to controls. A strong correlation between serum L-FABP concentrations and aspartate aminotransferases, alanine aminotransferases, HCV RNA levels and hepatic inflammation was found. When a cut-off value was 29,000 pg/mL for L-FABP, sensitivity and specificity were 75 and 100%, respectively. Positive and negative predictive values for L-FABP were 100 and 78%, respectively.

Conclusions

Serum L-FABP is used as a new diagnostic marker to detect liver injury.

Introduction

Hepatitis C virus (HCV) is one of the most important causes of chronic liver disease. HCV is a leading cause of chronic hepatitis, cirrhosis and liver cancer. Patients with severe hepatitis C who have high levels of the virus (HCV RNA) in serum and elevated serum enzymes may ultimately develop cirrhosis and end-stage liver disease. It has been estimated that ∼30% of patients with chronic hepatitis C (CHC) virus infection have persistently normal aminotransferase levels 1, 2. Several studies reported a significant progression of fibrosis in patients with normal alanine aminotransferase (ALT) and the development of hepatocellular carcinoma in some cases have been described despite persistent ALT normality 3, 4, 5, 6. Although liver biopsy has long been the gold standard for the evaluation of the status of liver disease in patients with CHC, whether subjects with persistently normal aminotransferase levels should routinely undergo liver biopsy is still extremely controversial because liver biopsy is an expensive and invasive procedure with serious complications.

Several studies investigated whether there was a relationship between laboratory parameters and the pathological pattern of a liver biopsy specimen in CHC. Unfortunately, biochemical and serological tests were superior at predicting no or minimal fibrosis or at predicting advanced fibrosis/cirrhosis and were poor at predicting intermediate levels of fibrosis 7, 8, 9, 10. Thus, further prospective studies are required to better define the usefulness of each marker or their combination.

Fatty acid-binding proteins (FABPs) are a group of low molecular weight (14–15 kDa) proteins involved in the intracellular transport of long-chain bioactive fatty acids (11). Being abundant low molecular weight cytoplasmic proteins with tissue specific expression profiles, FABPs hold promise to serve as markers of tissue injury. Various FABPs were tested to detect early damage of tissues with the clinical utility in view. If the damage process is continuous, FABP is detectable in serum 12, 13, 14, 15, 16, 17, 18, 19.

There are nine different FABPs with tissue-specific distribution that include liver, intestinal, muscle and heart, adipocyte, epidermal, ileal, brain, myelin, and testis 11, 20. Liver fatty acid-binding protein (L-FABP) has a low molecular weight (14 kDa) and is abundantly present in liver cells compared to other liver enzymes including ALT, aspartate aminotransferase (AST) (96 kDa) and glutathione S-transferase (26 kDa) (21). The properties of FABPs lead to increased levels in urine and/or serum even after minimal cell injury. In previous studies, urinary L-FABP levels were better suited to allow the accurate and earlier detection of both histological and functional insults compared with conventional renal markers 17, 18, 19. In the pertinent literature, there is only one study showing that L-FABP is a promising biochemical marker for the detection of hepatocellular injury in liver transplant patients (21). In another study, to detect the normal range of L-FABP, urinary excretions of L-FABP were analyzed in patients with chronic hepatitis (22). However, L-FABP was not previously evaluated in viral hepatitis C. The aim of this study was to determine whether serum L-FABP has diagnostic value in liver injury in chronic hepatitis C infection.

Section snippets

Materials and Methods

Patients who had persistently elevated serum aminotransferases >1.5-fold of the upper limit of the reference range (for at least 6 months) and were positive for serum HCV antibodies according to enzyme-linked immunosorbent assay and HCV RNA using polymerase chain reaction were included in the study. The study was approved by the local ethics committee.

Patients with hepatitis delta virus (HDV), hepatitis B virus (HBV), or human immunodeficiency virus (HIV) infections were excluded as were those

Results

A total of 42 subjects including 22 subjects with chronic hepatitis C and 20 healthy control patients were enrolled in this study. Age, gender distribution, body mass index, and prevalence of reported alcohol abuse did not differ among the patient groups. Clinical characteristics and some anthropometric indices and laboratory measurements of CHC patients and control groups are listed in Table 1.

CHC patients had significantly higher levels of AST, ALT, ALP, GGT levels (all p <0.05) than did the

Discussion

Our study showed that L-FABP was more reliable in demonstrating inflammatory activity of liver in CHC. There were positive correlations between L-FABP and aminotransferase and HCV RNA levels and inflammation of the liver. L-FABP seems to be an important marker to detect active chronic hepatitis C.

A few studies investigated L-FABP level in chronic liver diseases. Urinary L-FABP in chronic hepatitis was evaluated in a previous study where the authors reported an elevation of urinary L-FABP in

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