الفهرس 
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Abstract
Egypt is cursed with an immense burden of HCV related chronic liver diseases with its complications. The need of a newly noninvasive simple sensitive reliable and cheap diagnostic marker of different categories of liver disease, in spite of all efforts is still mandatory (Castera and Bedossa, 2011). LCN 2, also known as oncogene 24p3 or NGAL is a protein involved in innate immunity by sequestrating iron that in turn limits bacterial growth. It is expressed in neutrophils and in low levels in the kidney, prostate and epithelia of the respiratory and alimentary tract (Kim et al., 2010). Lipocalin-2 was found to be associated with increasing lobular inflammation, ballooning & fibrosis with an important role in pathogenesis of liver cirrhosis and HCC (Zimmermann et al., 2013). The aim of the present work was to evaluate the role of urinary lipocalin for diagnosis of the following aspects of liver disease:-
1- Liver fibrosis.
2- Non alcoholic steatohepatitis (NAFLD).
3- Spontaneous bacterial peritonitis (SBP).
4- Hepatocellular carcinoma (HCC).
To achieve this aim, our study was conducted on 200patients with different categories of liver diseases from the outpatient and inpatient units, of hepatology department, National Liver Institute, Menoufiya University from October 2013 to November 2014.
The patients were classified into the following groups:
1) Group-1: Forty (40) patients with chronic HCV, HBV& liver biopsy was done for all of them.
2) Group-2: Forty (40) patients with NAFLD & liver biopsy was done for all of them.
3) Group-3: Forty (40) cirrhotic patients with ascites and SBP which is determined by clinical examination, laboratory investigations and abdominal ultrasound.
4) Group-4: Forty (40) patients with HCC.The diagnosis of HCC was done by characteristic vascular enhancement pattern detected by multislice triphasic spiral CT scan or MRI according to established diagnostic criteria [EASL 2012] with or without elevated alfa fetoprotein more than 200 ng per ml.
5) Group-5: Forty (40) healthy control subjects.
All patients in this study were subjected to full history taking and thorough clinical examination and diagnostic tools including: liver function tests, renal function tests,Compete blood count, serum alfa fetoprotein (AFP) (in group 3), abdominal U/S, ultrasound guided liver biopsy for patients in group (1 and 2), Triphasic CT on abdomen &pelvis for HCC patients, urinary lipocaline-2 level was measured in all studied patients and in 40 apparently healthy subjects with no history or clinical evidence of liver disease or any other disease, served as a control group.
We found that:
- As regards fibrosis group: The urinary lipocalin level was (4338.48 ± 2778.47 pg/ml) while it was (238.46 ± 152.89 pg/ml) in the control group. So, there was statistically significant difference (p=0.001).
The stage of liver fibrosis was assessed according to the METAVIR fibrosis score; 31 patients (77.5 % ) had no or mild fibrosis (stages F0 and F1) and 9 patients (22.5 %) showed significant fibrosis (stages F2-F4) in the fibrosis group and results were that urinary LCN 2 level were higher in patients with no or mild fibrosis (F0-F2) than in patients with significant fibrosis (F2-F4), but these results were statistically insignificant (p= 0.208) and this may be due to small number of patients included in the study.
The mean value of lipocalin2 in patients with mild activity (A1) was (4476.85 ± 2941.97 pg/ml), while it was (3785 ± 2051 pg/ml) in patients with moderate activity (A2) group (P value = 0.536). So, lipocalin is high in both groups, but can´t differentiate between mild activity & moderate activity. So, LCN 2 has no correlation to the degree of inflammation and plays a major role as a non-invasive marker of liver fibrosis instead of liver biopsy which carries high risk to the patients.
At cutoff value of LCN 2 (880 pg/ml) in the diagnosis of liver fibrosis, the sensitivity, specificity of lipocalin was (90%), (100%) respectively, with PPV, NPV was (100%), (90%) respectively. The area under the curve was (0.9), and accuracy was (94.8), it was statistically significant (P-value =0.001) and CI = 0.993.
- As regard steatosis group in our study, the mean value of lipocalin in patients with NAFLD was (5070.94 ± 2787.80 pg/ml) while, in patients with NASH was (5148.57 ± 3632.56 pg/ml), but this difference wasn´t statistically significant (p=0.950).
SO, LCN2 is highly elevated in patients with steatosis but can´t differentiate between NAFLD &NASH and that may be due to the small number of patients who diagnosed to be NASH (9 patients) by liver biopsy.
At cutoff value of LCN 2(855 pg/ml), for the diagnosis of steatosis, sensitivity, specificity of lipocalin was (97.4 %), (100%) respectively, with PPV, NPV was (100%), (97.4%) respectively. The area under the curve was (0.974), and accuracy was (98.7), it was statistically significant (P-value =0.001) and CI = (1.0).
- As regards SBP group, the level of lipocalin was elevated in patients with spontaneous bacterial peritonitis. The mean value was (2546.66 ± 2773.24 pg/ml), while in the control group was (238.46 ± 152.89 pg/ml) and this difference was statistically significant (P=0.001).
At cutoff value of LCN 2 (850 pg/ml) for the diagnosis of SBP, The sensitivity, specificity of lipocalin was (85%), (100%) respectively, with PPV, NPV was (100%), (86%) respectively. The area under the curve was (0.854), and accuracy was (92.3), it was statistically significant (P-value =0.001) and CI = 0.962.
- As regards HCC group in our study ,we showed that urinary lipocalin level was highly elevated in patients with hepatocellular carcinoma and the mean value of lipocalin was (3661.43 ± 3258.71 pg /ml) with 95% sensitivity ,100% specificity and these results were statistically significant (p=0.001).
At cutoff value of LCN2 (860 pg/ml) for the diagnosis of HCC patients, the sensitivity, specificity of lipocalin was (95 %), (100%) respectively, with PPV, NPV was (100%), (94.9 %) respectively. The area under the curve was (0.950), and accuracy was (97.4), it was statistically significant (P-value =0.001).
In comparison, the sensitivity, specificity of AFP at cutoff level value (22 ng/ml), was (87.5%), (81.1), PPV (83.3%), NPV (85.7%)
respectively. The area under the curve was (0.927), and accuracy was (84.4), it was statistically significant (P-value =0.001) and CI was (1.0).
When adding AFP with lipocalin at cutoff value (1003 pg/ml), the sensitivity and specificity was (95%), (100%), respectively, with PPV, NPV was (100%), (94.9%), respectively .The area under the curve was (0.950) and accuracy was (97.4), it was statistically significant (P-value = 0.001) and CI = (1.0)