Liver Fatty Acid Binding Protein Levels Research Articles

Liver Fatty Acid-binding Protein Is a More Reliable Biomarker for Liver Injury in Nonalcoholic Steatohepatitis than Other Etiologies of Hepatitis.

Liver fatty acid-binding protein (LFABP) controls hepatocyte lipid metabolism and can be a biomarker in liver diseases. We compared the correlation of LFABP levels with liver histology in viral hepatitis and nonalcoholic fatty liver disease (NAFLD) and investigated the utility of serum LFABP as a biomarker for liver damage. We included 142 patients (60 chronic viral hepatitis B [CHB], 35 chronic viral hepatitis C [CHC], 47 NAFLD) and 40 healthy controls. LFABP levels were determined in all participants, and a liver biopsy was performed on patients. The nonalcoholic steatohepatitis (NASH) activity score (NAS), hepatosteatosis, liver inflammation, and fibrosis were evaluated for NAFLD patients. Ishak's histological scores were used for viral hepatitis. The correlation between LFABP levels and histologic scores was assessed in each group. Serum LFABP levels in CHB, CHC, NAFLD, and control groups were 2.2, 3.5, 7.6, and 2.1 ng/mL, respectively. LFABP levels were significantly higher in the NAFLD group compared to the control, CHC, and CHB groups. LFABP was significantly higher in the NASH group than in nonalcoholic steatohepatitis, 8 ng/mL and 5.4 ng/mL, respectively (P = .001). In the NAFLD group, LFABP levels showed a moderate positive correlation with NAS score (r = 0.58, P <.001), ballooning degeneration (r = 0.67, P <.001), and lobular inflammation (r = 0.62, P <.001). A logistic regression study showed that the level of LFABP was predictive of NASH independent of age, gender, homeostasis model of IR, body mass index, aspartate aminotransferase, and alanine aminotransferase (OR = 1.869, P = .01). LFABP specifically correlates with liver histology in NAFLD compared to viral hepatitis. Additionally, it can distinguish NASH from simple steatosis. LFABP may be a valuable biomarker for hepatocyte injury in NASH.

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From the Editor’s Desk...

Urinary L-FABP is a promising prognostic biomarker of ACLF and mortality in patients with decompensated cirrhosis

Decompensated cirrhosis (DC) is associated with high mortality, mainly owing to the development of acute-on-chronic liver failure (ACLF). Identifying the patients with DC who are at high risk of mortality and ACLF development is an unmet clinical need. Liver fatty acid-binding protein (L-FABP) is expressed in several organs and correlates with liver and systemic inflammation. Herein, we aimed to assess the prognostic value of L-FABP in patients with DC. A prospective series of 444 patients hospitalized for DC was divided into 2 cohorts: study cohort (305 patients) and validation cohort (139 patients). L-FABP was measured in urine and plasma samples collected at admission. Neutrophil gelatinase-associated lipocalin (NGAL) was also measured in urine samples for comparison. Urine but not plasma L-FABP correlated with 3-month survival on univariate analysis. On multivariate analysis, urine L-FABP and model for end-stage liver disease (MELD)-Na were the only independent predictors of prognosis. Urine L-FABP levels were higher in patients with ACLF than in those without and also predicted the development of ACLF, together with MELD-Na, during follow-up. In patients with ACLF, urine L-FABP correlated with liver, coagulation, and circulatory failure. Urine L-FABP levels were also increased in patients with acute kidney injury, particularly in those with acute tubular necrosis. The ability of urinary L-FABP to predict survival and ACLF development was confirmed in the validation cohort. Urine NGAL predicted outcome on univariate but not multivariate analysis. Urinary L-FABP levels are independently associated with the 3-month clinical course in patients with DC, in terms of mortality and ACLF development. Urinary L-FABP is a promising prognostic biomarker for patients with DC. Increased levels of liver fatty acid-binding protein (L-FABP), a protein related to lipid metabolism, have been associated with liver-related diseases. The present study analyzed urinary L-FABP levels in 2 independent groups of patients with decompensated cirrhosis and showed that higher urinary L-FABP levels correlated with increased mortality and risk of acute-on-chronic liver failure development. Therefore, urinary L-FABP levels could be useful as a new tool to predict complications in patients with decompensated cirrhosis.

Liver Fatty Acid Binding Protein: Is it an early diagnostic and prognostic marker in liver damage?

Objective: The majority of the liver function tests are not specific to the liver. The histological liver damage begins before patients are diagnosed with cirrhosis and continues afterwards. Therefore, there is an increasing demand for early and specific markers that are correlated with liver damage. This study aims to investigate if serum and urinary liver fatty acid-binding protein (L-FABP) levels could be used as an early diagnostic marker of liver cirrhosis.&#x0D; Material and Methods: This cross-sectional study included 30 patients with compensated liver cirrhosis, 27 patients with decompensated liver cirrhosis, and 30 healthy controls. The patients and healthy controls were tested for serum and urinary L-FABP levels.&#x0D; Results: The serum and urinary L-FABP levels were higher in patients with cirrhosis than the healthy controls (both p&lt;0.001). The cut-off value of serum and urinary L-FABP was computed as 721.78 ng/ml and 621.25 ng/ml, respectively. The sensitivity of serum and urinary L-FABP to detect cirrhosis at this cut-off was 99.8% and 98.9%. The specificity, positive predictive value, and negative predictive value of serum and urinary L-FABP at these cut-off levels were 100 %. There was no difference in terms of serum and urinary L-FABP between compensated and decompensated cirrhosis patients. Accordingly, no correlation was determined between serum/urinary L-FABP levels and cirrhosis complications.&#x0D; Conclusion: L-FABP increases in serum and urine in response to hepatocyte damage that can result in liver fibrosis. We demonstrated that patients with liver cirrhosis had high L-FABP levels. L-FABP may be used as a predictive non-invasive marker of cirrhosis as it can be detected before the clinical symptoms of liver damage.

Adipocytokines as Risk Factors for Development of Nonalcoholic Fatty Liver Disease in Children

Noninvasive diagnostics of nonalcoholic fatty liver disease (NAFLD), the most common cause of liver dysfunction in children, are based on imaging, biochemical testsand their compilation. The study aimed to evaluate the serological biomarkers of steatosis, inflammation and liver fibrosis to assess the risk of NAFLD in children. A total of 73 children were included in the prospective study; 50 of them were diagnosed with NAFLD based on ultrasound, and 23 formed a control group. Basic anthropometric parameters were measured, blood samples were taken for laboratory tests and evaluated proteins were assessed by enzyme-linked immunosorbent assay-adiponectin, tumour necrosis factor alpha, fibroblast growth factor 21, liver fatty acid-binding protein (L-FABP) and interleukin 6. Statistically significant differences between the levels of two proteins were found: the adiponectin level was lower in the NAFLD group (12.24 ± 7.01 vs 16.88 ± 9.21μg/mL, P= 0.024), and L-FABP levels were higher (21.48 ± 20.61 vs 11.74 ± 8.39ng/mL, P= 0.031). In the group of children with body mass index (BMI)-for-age >1 standard deviation (SD), adiponectin concentration was also significantly lower (12.18 ± 6.43μg/mL) than in the group with BMI≤1 SD (17.29 ± 9.42μg/mL, P= 0.015). The odds ratios and 95% confidence interval for the relation between adiponectin and NAFLD and obesity were 0.868 (0.767-0.982) and 0.838 (0.719-0.977), respectively. Adiponectin may be useful in evaluating the risk of NAFLD and obesity in children.

Diacerein protects rats with liver ischemia/reperfusion damage: Down-regulation of TLR4/ NFκ-B signaling pathway

PurposeLiver ischemia-reperfusion (I/R) injury is an inescapable problem. Diacerein, a chondro-protective drug, has antioxidant and anti-inflammatory effects. Its effect on liver I/R injury has not yet been fully clarified. Therefore, the current study aimed to detect its hepatic protective effect with the explanation of possible underlying mechanisms. MethodsAdult male albino rats were assigned to 4 groups: sham group, diacerein pretreated sham group, I/R non-treated group, and I/R diacerein pretreated group. Serum liver enzymes, hepatic tissue oxidative stress parameters, inflammatory biomarkers mainly Toll-like receptors-4 (TLR4), and liver fatty acid binding protein (L-FABP) levels were determined. Histopathological examination of liver tissues and immunohistochemical studies of heat shock protein 70, nuclear factor-kappa B, and Cluster of Differentiation 68 were also done. ResultsDiacerein pretreatment has the ability to restore the hepatic I/R damaging effect, proved by the reduction of serum liver enzymes, the decrease of the oxidative stress and hepatic inflammation via down-regulation of TLR4/ NFκ-B signaling pathway together with the restoration of L-FABP level and improvement of the histopathological and immunohistochemical study findings in the hepatic tissue. ConclusionThese results suggested the hepatoprotective effect of diacerein relies on its antioxidant and anti-inflammatory effects reducing TLR4/ NFκ-B signaling pathway.

Analysis of the association between kidney injury biomarkers concentration and nephritis in immunoglobulin A vasculitis: A pediatric cohort study

The aim of this study was to investigate the clinical course, selected biochemical parameters and concentrations of renal injury biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1) and liver-fatty acid binding protein (L-FABP) in patients with immunoglobulin A vasculitis (IgAV) to identify the markers associated with nephritis in the course of the disease (IgAVN). The study involved 29 children with IgAV and 34 healthy controls. Eleven (38%) patients had renal involvement (IgAV-N) and 18 (62%) did not exhibit nephritis (IgAV-noN). Initial laboratory tests, determining the concentrations of NGAL, KIM-1 and L-FABP in serum and urine, were conducted on children from the study group in an acute phase of IgAV as well as after an average of 6months, during a follow-up visit. The interconnection between renal involvement, anthropometric measurements, epidemiological data, laboratory parameters and levels of examined biomarkers have been thoroughly evaluated. The serum and urine levels of NGAL, KIM-1 and L-FABP were significantly higher in children with an acute phase of IgAV as compared to the control group (P<.001) and markedly lower during follow-up retesting in comparison with the values obtained at inclusion (P<.001). However, the concentration of none of the evaluated biomarkers correlated with nephrological indices. Among all examined parameters, only male subjects were associated with nephritis (P=.017). We have established no evident association between the concentrations of NGAL, KIM-1 and L-FABP and nephritis in the course of IgAV in children. Additionally, we confirmed a significant male predominance in patients with nephritis.

Assessment of Liver Fatty Acid Binding Protein (L-FABP) as a Diagnostic Marker in Non-Alcoholic Fatty Liver Disease

Background: Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common liver disease worldwide, it causes chronic hepatitis, which leads to cirrhosis and hepatocellular carcinoma. We aimed to assess the value of liver fatty acid binding protein (L-FABP) in the diagnosis of non-alcoholic fatty liver disease in comparison to ultrasonography. Patients and Methods: Ninty subjects were enrolled in this study who attended the Hepatology, Gastroenterology and Internal medicine clinics in Benha University Hospitals between January 2017 and January 2018 and divided into group I included 70 consecutive patients with non-alcoholic fatty liver disease who were diagnosed by ultrasound with or without elevated liver enzymes and group II included 20 healthy control subjects without NAFLD (by ultrasound) with normal liver enzymes. Serum levels of L-FABP were determined by enzyme-linked immunosorbent assay. Results: NAFLD patients were slightly older than healthy subjects as mean age in group I was (37.74 ± 11.7) while in group II was (36.5 ± 11.31). There was a slight increase in NAFLD in males, there was a high prevalence of NAFLD in the urban population. L-FABP levels in NAFLD patients were higher than in the control group (levels were 188.6 ± 34.94 and 137.7 ± 13.05 ng/l respectively). A strong correlation was found between L-FABP and ALT, AST, BMI and glucose levels. Analysis of ROC curve revealed that at a level 151.1 ng/sensitivity, specificity, PPV, NPV and accuracy were 83.3%, 71.8%, 31.3%, 96.6% and 73.3% respectively with AUC 0.839 and at a level 189.5 ng/sensitivity, specificity, PPV, NPV and accuracy were 90%, 90%, 95.4%, 95.4%, 88.9% with AUC was 0.950. Conclusion: Serum L-FABP could be used as a new diagnostic biomarker for detecting NAFLD.

Urine biomarkers of chronic kidney damage and renal functional decline in childhood-onset systemic lupus erythematosus.

To delineate urine biomarkers that reflect kidney structural damage and predict renal functional decline in pediatric lupus nephritis (LN). In this prospective study, we evaluated kidney biopsies and urine samples of 89 patients with pediatric LN. Urinary levels of 10 biomarkers [adiponectin, ceruloplasmin, kidney injury molecule-1, monocyte chemotactic protein-1, neutrophil gelatinase-associated lipocalin, osteopontin, transforming growth factor-ß (TGFß), vitamin-D binding protein, liver fatty acid binding protein (LFABP), and transferrin] were measured. Regression analysis was used to identify individual and combinations of biomarkers that determine LN damage status [NIH-chronicity index (NIH-CI) score ≤ 1 vs. ≥ 2] both individually and in combination, and biomarker levels were compared for patients with vs. without renal functional decline, i.e., a 20% reduction of the glomerular filtration rate (GFR) within 12months of a kidney biopsy. Adiponectin, LFABP, and osteopontin levels differed significantly with select histological damage features considered in the NIH-CI. The GFR was associated with NIH-CI scores [Pearson correlation coefficient (r) = - 0.49; p < 0.0001] but not proteinuria (r = 0.20; p > 0.05). Similar to the GFR [area under the ROC curve (AUC) = 0.72; p < 0.01], combinations of osteopontin and adiponectin levels showed moderate accuracy [AUC = 0.75; p = 0.003] in discriminating patients by LN damage status. Renal functional decline occurred more commonly with continuously higher levels of the biomarkers, especially of TGFß, transferrin, and LFABP. In combination, urinary levels of adiponectin and osteopontin predict chronic LN damage with similar accuracy as the GFR. Ongoing LN activity as reflected by high levels of LN activity biomarkers heralds renal functional decline. • Levels of osteopontin and adiponectin measured at the time of kidney biopsy are good predictors of histological damage with lupus nephritis. • Only about 20% of children with substantial kidney damage from lupus nephritis will have an abnormally low urine creatinine clearance. • Continuously high levels of biomarkers reflecting lupus nephritis activity are risk factors of declining renal function.

PP.07.21] KIDNEY INJURY, VASCULAR REACTIVITY AND STIFFNESS IN GENDER SUBGROUPS OF HYPERTENSIVE PATIENTS

Objective: Chronic renal disease and hypertension are strongly associated with vascular damage, endothelial dysfunction (ED) and increased vascular stiffness. We hypothesized that several novel, potentially more sensitive biomarkers of kidney damage may be differently related to vascular stiffness and reactivity in male and female patients with different severity of hypertension. Design and method: Urine levels of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver fatty-acid binding protein (L-FABP) and serum levels of Cystatin C (sCys) and serum creatinine (sCr) were measured by quantitative enzyme immunoassay in 92 hypertensive patients, 46 males (mean age 46,3 ± 13,4 years) and 46 females (mean age 55,2 ± 8,9 years). Renal function (GFR) was analyzed using MDRD and the CKD Epidemiology Collaboration (EPI) sCr equation and CKD-EPI sCys equation. Instrumental examination was performed after 5 days of discontinuation of antihypertensive medications including applanation tonometry (SphygmoCor, Artcor Medical) with the calculation of central aortic pressure, pulse wave velocity (PWV) and augmentation index (AI). Endothelial function was assessed by reactive hyperemia index (RHI) with EndoPAT device (Itamar Medicals). Results: Female patients were characterized by higher NGAL (16.6 +/− 12.8 versus 6.0 +/− 4.3 ng/ml, respectively; p = 0.0001) and lower sCys-estimated GFR (88.0 +/− 14.1 mL/min/1.73 m2 versus 95.6 +/− 19.1; p = 0.04), while there were no differences in sCr-estimated GFR, KIM-1, L-FABP and Cystatin C levels. There were also no differences in RHI and PWV levels between groups. In females novel biomarkers levels were associated with increased arterial stiffness (PVW > 10 m/s): sCys-estimated GFR (r = 0.351, p = 0.02), Cystatin C and L-FABP (r = 0.285, p = 0.06; r = 0.405, p = 0.01, respectively). In males patients Cystatin C and L-FABP levels were associated with lower RHI (r = −0,704, p = 0.005; r = −0.651, p = 0.03, respectively), KIM-1 levels were associated with increased PWV (r = 0.612, p = 0.06) only in patients with severe and resistant hypertension. Conclusions: Cystatin C and L-FABP seem to be associated with increased arterial stiffness in hypertensive females and vascular reactivity in severe, resistant to treatment hypertensive males. Arterial stiffness in males is linked mostly to KIM-1 levels.

Prediction of contrast-induced acute kidney injury by early post-procedural analysis of urinary biomarkers and intra-renal Doppler flow indices in patients undergoing coronary angiography.

The study was designed to evaluate the applicability of combined assessment of urinary biomarkers and intra-renal Doppler flow indices for the prediction of contrast-induced acute kidney injury (CI-AKI) after coronary angiography/percutaneous coronary interventions (CA/PCI). This prospective observational study covered 95 consecutive patients with coronary artery disease subject to elective or urgent CA/PCI. Doppler intra-renal flow indices were assessed before and 1 h following CA/PCI. Urine samples were collected within 24 h before and 6 h after CA/PCI and assayed for urinary interleukin-18 (IL-18), liver-fatty acid-binding protein (L-FABP), and kidney injury molecule-1 (KIM-1) using ELISA method. CI-AKI was defined as ≥50% relative or ≥0.3 mg/dL absolute increase of serum creatinine concentration at 48 h post-procedurally. CI-AKI was confirmed in nine patients (9.5%). CI-AKI onset was associated with significantly higher urinary KIM-1 at 6 h (P = 0.003) and ΔKIM-1 concentrations (P = 0.001), and urinary IL-18 at 6 h (P = 0.014) and ΔIL-18 concentrations (P = 0.012), however, L-FABP and ΔL-FABP levels were comparable in both groups. Receiver operating characteristic curve analysis denoted that post-procedural IL-18 levels at 6 h >89.8 pg/mg (AUC = 0.75, P = 0.007), KIM-1 at 6 h >0.425 ng/mg (AUC = 0.81, P = 0.001), renal resistive index (RRI) at 1 h >0.73 (AUC 0.88; P < 0.0001), and renal pulsatility index (RPI) at 1 h >0.86 (AUC = 0.86; P < 0.0001) predicted CI-AKI onset. Logistic regression analysis of postoperative predictors revealed that IL-18 and RRI were independent predictors of CI-AKI onset (AUC = 0.96; P < 0.0001). Joint assessment of early post-procedural urinary biomarkers and Doppler renovascular parameters aids early diagnosis of CI-AKI in patients undergoing coronary interventions.

The Importance of Liver-Fatty Acid Binding Protein in Diagnosis of Liver Damage in Patients with Acute Hepatitis.

Acute hepatitis is acute inflammation of liver elicited by a large number of causes. It sometimes spontaneously recovers, sometimes may progress to chronic hepatitis. Liver- Fatty Acid Binding Protein (L-FABP) is a small protein that is abundant in hepatocytes, and which binds most of the long-chain fatty acids present in the cytosol. The present study was aimed to investigate the levels of serum and urine L-FABP in acute hepatitis and diagnostic value of serum and urine L-FABP levels in patients with acute hepatitis. The present study included a total of 85 patients. Total number of patients with acute hepatitis were 17 (five of acute hepatitis B, one of acute hepatitis A, two of acute hepatitis C, five of autoimmune hepatitis and four of toxic hepatitis), 19 of hepatic encephalopathy, 29 of liver cirrhosis, and 20 controls were included. Serum and urinary L-FABP levels were analyzed by the Enzyme-Linked Immunosorbent Assay (ELISA). Serum L-FABP levels were 9110±3352.5, 9410±1355, 9715±2462 and 3672±982.5 ng/l in patients with acute hepatitis, hepatic encephalopathy and cirrhosis and control subjects, respectively. There were statistically significant positive correlations between serum levels of L-FABP and Aspartate Aminotransferases (AST), Alanine Aminotransferases (ALT), Creatinine (Cre) and Gamma Glutamyl Transferases (GGT) (p<0.001, p<0.001, p<0.001 and p<0.001, respectively). While the cut-off value of serum L-FABP for all of the patients was 5183 ng/l {p<0.001 and Area Under Curve (AUC) 0.985}, the sensitivity and specificity were 95.4% and 100%, respectively. Positive and negative predictive values for serum L-FABP were 100% and 87%, respectively. Serum and urine L-FABP may be a new diagnostic marker for liver damage in patients with acute hepatitis. However, our study showed that except of aminotransferases, L-FABP should be used for diagnosis of liver damage in patients with acute hepatitis, chronic hepatitis and also cirrhosis.

PP.09.13] NOVEL BIOMARKERS OF KIDNEY INJURY IN PATIENTS WITH DIFFERENT SEVERITY OF HYPERTENSION

Objective: Hypertension still remains one of the leading causes of end-stage renal disease and early detection of kidney injury may have a dramatic impact on treatment strategy and patient's prognosis. The aim of the present study was to assess whether novel biomarkers may facilitate early detection of kidney injury in patients with different severity of hypertension. Design and method: Urine levels of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver fatty-acid binding protein (L-FABP) and serum levels of Cystatin C and creatinine were measured by quantitative enzyme immunoassay in 92 hypertensive patients, divided into four age and sex-matched groups according to severity of hypertension: 1 grade (n = 24), 2 grade (n = 26), 3 grade (n = 17) and resistant hypertension (n = 25). Glomerular filtration rate (GFR) was estimated by MDRD and CKD-EPI formulas. Instrumental examination was performed after 5 days of discontinuation of antihypertensive medications and included ambulatory blood pressure monitoring (ABPM, SpaceLabs 90207). Results: There were no differences in NGAL, KIM-1, creatinine levels, and eGFR between groups. Patients with 1, 2, 3 grades of hypertension had no differences in Cystatin C (0.86 +/- 0.1; 0.85 +/- 0.14; 0.86 +/- 0.06 pg/ml respectively; p > 0.05) and L-FABP (1997.8 +/- 1657.2; 2412.5 +/- 1487.1; 1756.7 +/- 1949.8 pg/ml respectively; p > 0.05) levels. While patients with resistant hypertension are predisposed to advanced organ damage were characterized by higher Cystatin C (0.97 +/- 0.18 pg/ml; p = 0.01) and L-FABP (9270.2 +/- 30394.5 pg/ml; p = 0.05) levels, associated with mean 24-hours systolic blood pressure (BP) level (r = 0.246, p = 0.03 and r = 0.339, p = 0.006 respectively). Conclusions: Cystatin C and L-FABP seem to be potentially more sensitive biomarkers of kidney injury, and their levels increase with the severity of hypertension.

Mass spectrometric quantification of urinary human liver fatty acid binding protein in renal transplant recipients.

Urinary liver fatty acid binding protein (L-FABP) has been evaluated as a promising early biomarker of renal ischemia in human kidney transplant patients. The use of L-FABP in clinical practice requires that this biomarker be associated with an analytical method that combines specificity, accuracy and robustness. This study aimed to evaluate an optimized multiple reaction monitoring (MRM) method using ultrafast liquid chromatography coupled with tandem mass spectrometry to measure urinary L-FABP levels in renal transplant recipients. Purified recombinant human L-FABP tryptic standard was analyzed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS/MS) and liquid chromatography (LC)/MS/MS to select for peptides that provided specificity and adequate response in developing an MRM method for urinary L-FABP quantification. Human urine samples collected from kidney transplant recipients were isolated, concentrated, precipitated and trypsin digested before mass spectrometric analysis of L-FABP. L-FABP levels were also measured in urine samples by enzyme immunoassay. The tryptic peptide ion MH(+) of (50) FTITAGSK(57) (m/z 824) provided an adequate signal and was used for quantification of L-FABP under conditions employed for LC/MS/MS analysis. MALDI-TOF-MS/MS spectra obtained by collision-induced dissociation of the parent MH(+) ion (50) FTITAGSK(57) resulted in a y3 product ion that was used for quantitative analysis by the MRM method. Urinary L-FABP content measured by both ELISA and LC/MS/MS after transplantation was significantly higher compared to before transplantation levels. The Spearman correlation coefficient between the two methods was statistically significant. Intra-day and inter-day coefficients of variation provided good repeatability and reproducibility for validation of LC/MS/MS analysis. LC/MS/MS quantification of L-FABP may provide a new reference method to determine changes in this potential biomarker in human kidney transplant patients.

Liver Fatty Acid Binding Protein And Hemojuvelin - Potential Biomarkers For Liver Function in Rat Model.

Purpose. The purpose of the present study was to investigate whether the co-administration of aripiprazole and fluoxetine could produce impaired liver function in Wistar rats by means of liver fatty acid binding protein (L-FABP) and hemojuvelin (HJV) serum levels. Furthermore, the experiment intended to assess the salivary levels of L-FABP and HJV and to determine whether they correlate with the serum levels of the two markers. Materials and Methods. Adult male Wistar rats were randomly assigned to four groups: control (saline 10ml/kg), aripiprazole (4.05 mg/kg), fluoxetine (10 mg/kg) and aripiprazole + fluoxetine (4.05 mg/kg + 10 mg/kg). The drugs were administered by gavage, daily at the same hour, along a 6 week period. L-FABP and HJV levels were determined in serum, from intraventricular blood, and in saliva. Also from intraventricular blood, serum levels for aspartate aminotransferase (ASAT) and alanine amino transferase (ALAT) were assessed. Results. Positive and statistically significant correlations between serum and salivary levels of L-FABP and HJV were found. Aripiprazole + fluoxetine group experienced increased serum L-FABP levels than aripiprazole and fluoxetine groups, and salivary L-FABP as compared to aripiprazole group; but it registered decreased levels for serum and salivary HJV, for ASAT and ALAT than aripiprazole and fluoxetine groups, and for salivary L-FABP compared to fluoxetine group. Conclusions. The data indicate that: aripiprazole coprescribed with fluoxetine do not cause additional alterations in liver function; L-FABP and HJV levels can be helpful as biomarkers for impaired function of hepatocytes; and that their salivary determination can replace serum determination.

Role of a liver fatty acid-binding protein gene in lipid metabolism in chicken hepatocytes.

This study investigated the role of the chicken liver fatty acid-binding protein (L-FABP) gene in lipid metabolism in hepatocytes, and the regulatory relationships between L-FABP and genes related to lipid metabolism. The short hairpin RNA (shRNA) interference vector with L-FABP and an eukaryotic expression vector were used. Chicken hepatocytes were subjected to shRNA-mediated knockdown or L-FABP cDNA overexpression. Expression levels of lipid metabolism-related genes and biochemical parameters were detected 24, 36, 48, 60, and 72 h after transfection with the interference or overexpression plasmids for L-FABP, PPARα and L-BABP expression levels, and the total amount of cholesterol, were significantly affected by L-FABP expression. L-FABP may affect lipid metabolism by regulating PPARα and L-BABP in chicken hepatocytes.

The effect of acute alcohol intoxication on gut wall integrity in healthy male volunteers; a randomized controlled trial

The aim of the study is to determine the effect of acute alcohol consumption on enterocytes. Chronic alcohol consumption has been known to induce a decrease in gut wall integrity in actively drinking alcoholics and patients with alcohol-induced liver disease. Data on the extent of the damage induced by acute alcohol consumption in healthy human beings is scarce. Studies show that heavy incidental alcohol consumption is a growing problem in modern society. Data on this matter may provide insights into the consequences of this behavior for healthy individuals. In a randomized clinical trial in crossover design, 15 healthy volunteers consumed water one day and alcohol the other. One blood sample was collected pre-consumption, five every hour post-consumption, and one after 24 h. Intestinal fatty acid binding protein (I-FABP) was used as a marker for enterocyte damage. Liver fatty acid binding protein (L-FABP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT) were used as markers for hepatocyte damage. Lipopolysaccharide binding protein (LBP) and soluble CD14 (sCD14) were used as a measure of translocation. Interleukin-6 (IL-6) was used to assess the acute inflammatory response to endotoxemia. Alcohol consumption caused a significant increase in serum I- and L-FABP levels, compared to water consumption. Levels increased directly post-consumption and decreased to normal levels within 4 h. LBP, sCD14, and IL-6 levels were not significantly higher in the alcohol group. Moderate acute alcohol consumption immediately damages the enterocyte but does not seem to cause endotoxemia.

Liver fatty acid-binding protein as a diagnostic marker for non-alcoholic fatty liver disease.

Liver fatty acid-binding protein (L-FABP) is a small cytoplasmic protein. The aim of the current study was to investigate L-FABP levels and to determine their diagnostic value for non-alcoholic fatty liver disease (NAFLD). We enrolled in this study 24 consecutive patients with NAFLD who were diagnosed with elevated transaminases and with steatosis by ultrasonograph. The control group consisted of 22 healthy control subjects matched for age and gender. Serum levels of L-FABP were determined by enzyme-linked immunosorbent assay. L-FABP levels in NAFLD patients were higher than in the control group (levels were 41,976 ± 18,998 and 17048 ± 5021 pg/mL, respectively). A strong correlation was found between serum L-FABP concentrations and aspartate aminotransferase, alanine aminotransferase, body mass index, glucose and γ-glutamyltransferase levels. A level of 284,000 pg/mL L-FABP had 73% sensitivity and 100% specificity. Positive and negative predictive values for L-FABP were 100 and 79%, respectively. Serum L-FABP can be considered as a new diagnostic marker for detecting non-alcoholic fatty liver disease.

Abstract 18375: Urinary Liver Fatty-acid Binding Protein Within 24 Hours from Contrast Media Exposure May Predict Acute Kidney Injury

Introduction: Contrast-induced acute kidney injury (CI-AKI) is one of major complication of contrast medium exposure. However, few biological markers the day after contrast media exposure rapidly predict CI-AKI. Urinary liver fatty-acid binding protein (L-FABP), as a novel marker of renal ischemia and stress, has been reported to elevate in CI-AKI. Hypothesis: We tested the hypothesis that L-FABP within 24 hours from contrast media procedure predicted CI-AKI. Methods: A total of 160 patients who underwent invasive catheterization or coronary CT angiography were examined the study. Urinary liver fatty-acid binding protein within a day after the procedure was measured. Serum creatinine level within 72 hours were compared to baseline. CI-AKI was defined as laboratory increase of serum creatinine value =25% or &gt;=0.5mg/dl from baseline at 72 hours. Results: Estimated glomerular filtration rate of all patients averaged 69±24 ml/min/1.73m2. L-FABP level averaged 11.9±27μg /gCr. On receiver operating characteristics (ROC) analysis, cut-off value was 14.3μg /gCr and the area under the curve (AUC) was 0.739 (95 % CI: 0.576-0.902, P = 0.01). Negative predictive value for predicting CI-AKI was 0.99. Conclusions: L-FABP within 24 hours from contrast media procedure may predict CI-AKI with quite high negative predictive value.

Is there an association between liver type fatty acid binding protein and severity of preeclampsia?

The aim of this study was to estimate the level of liver fatty acid binding protein (LFABP) in women with preeclampsia. A case-control study was conducted in 90 pregnant women who were divided into the following three groups: normal pregnancy (n = 30), mild-moderate preeclampsia (n = 30), and severe preeclampsia (n = 30). Maternal blood samples were obtained during an antenatal clinic visit in normal pregnant women, and at the time of diagnosis in women with preeclampsia. Serum LFABP levels were measured by the quantitative sandwich enzyme immunoassay technique. Serum LFABP level was significantly higher in severe and mild-moderate preeclampsia groups than normal pregnancy group (1,709.90 ± 94.82, 1,614.93 ± 118.22, and 1,532.36 ± 140.98 pg/ml, respectively; p < 0.001). In multivariate analysis, the severity of preeclampsia was correlated with LFABP level [unadjusted odds ratio (95% confidence interval), 1.008 (1.003-1.012), p < 0.001 and LDH 1.063 (1.029-1.099), p < 0.001]. Maternal serum LFABP level appears to be correlated with the severity of the preeclampsia and can be used to confirm the diagnosis.