Serum Amyloid A as a non-invasive predictive biomarker of mucosal healing in ulcerative colitis patients.

Ulcerative colitis is a chronic immune-mediated inflammatory condition of large intestine that is frequently associated with inflammation of the rectum but often extends proximally to involve other areas of the colon. The ultimate target of therapy is complete healing in the form of clinical remission, complete endoscopic and histological healing, and transmural healing for which endoscopy is mandatory. Colonoscopy may not always be applicable due to possible complications in active ulcerative colitis. Therefore, non-invasive biomarkers are needed to avoid the disadvantageous complications of invasive diagnostic procedures. The aim of this study was to evaluate the role of serum Amyloid-A (SAA) as a non-invasive predictive biomarker of mucosal healing in comparison to different laboratory biomarkers, and endoscopic activity scores. The study included 100 ulcerative colitis patients classified into two groups: 50 patients in clinical, and biochemical remission and 50 patients in activity. Complete blood picture, C-reactive protein, erythrocyte sedimentation rate, fecal calprotectin, and SAA were measured and recorded, colonoscopies with histopathological examination were done for all patients. SAA levels were significantly higher in patients with active ulcerative colitis than in clinical remission patients (p < 0.001). In clinical, remission patients without full mucosal healing, SAA was positively correlated with endoscopic disease activity represented with Mayo score, Mayo endoscopic sub-score and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) (p < 0.001). However, there was no significant correlation between SAA and endoscopic scores among the activity patients' group. The cut off value of SAA for determining disease activity was > 5.199 µg/ml with 100 % sensitivity, specificity of 92 %, and accuracy of 99.6%. In conclusion, SAA can be used for prediction of mucosal healing in ulcerative colitis remission patients despite not being superior to fecal calprotectin. However, it was unable to differentiate between the different disease activities or extents.

Programmed death-ligand 1 (PD-L1) polymorphisms as predictive biomarkers for the development of liver cirrhosis and hepatocellular carcinoma in HCV Egyptian patients.

BACKGROUND: Considering the immune evasion role of programmed death-ligand 1 (PD-L1) in cancer development, its genomic variations might be closely associated with disease development and cancer risks. Accordingly, this study was performed to investigate how the PD-L1 gene polymorphisms affect the susceptibility to hepatitis C virus (HCV)-induced liver cirrhosis and cancer development in the Egyptian population. METHODOLOGY: Two single nucleotide polymorphisms of the PD-L1 gene; rs2297136 (A > G) and rs4143815 (C > G), were studied in 50 HCV, 51 liver cirrhosis, and 52 hepatocellular carcinoma (HCC) patients as well as 50 healthy subjects using real-time PCR. RESULTS: The frequencies of PD-L1 rs2297136 AA and rs4143815 GG genotypes were significantly higher in the liver cirrhosis than the control and HCV groups. The rs4143815 CG and GG genotypes were linked to a higher risk of developing HCC and were positively associated with the clinicopathological features of HCC. CONCLUSIONS: The PD-L1 rs2297136 AA and rs4143815 GG genotypes increase the susceptibility to liver cirrhosis. The rs4143815 CG and GG genotypes are positively associated with HCC risk and its clinicopathological characteristics. Therefore, HCV patients carrying the PD-L1 rs4143815 G-allele should be followed up on a regular basis to allow for early HCC management.

Serum clusterin as a promising diagnostic and prognostic marker for hepatocellular carcinoma after locoregional treatment.

Hepatocellular carcinoma (HCC) is one of the most common aggressive tumors, with a rising prevalence in Egypt. Clusterin is a secretory heterodimeric glycoprotein linked to cancer development and progression. This study was conducted to evaluate the diagnostic and prognostic role of serum clusterin as a possible biomarker of HCC and correlate its level with the mRECIST scoring system. This study included 45 patients with liver cirrhosis and HCC eligible for locoregional treatment and 20 patients with liver cirrhosis without HCC as controls. All patients underwent standard laboratory tests and abdominal ultrasound. For HCC patients, a triphasic CT scan, alpha-fetoprotein (AFP), and clusterin levels were measured at baseline and one month after intervention. HCC patients had a substantially higher baseline clusterin level than cirrhotic patients (122.291 ± 61.898 vs. 74.015 ± 41.571, P = 0.002). Five patients in the HCC group were not eligible for intervention because they had evidence of portal vein invasion. At one month follow-up after HCC treatment, serum clusterin levels declined significantly from baseline (from 122.291 ± 61.898 to 81.125 ± 62.321, P = < 0.001). According to the mRECIST scoring, baseline clusterin levels were significantly higher among patients with progressive disease than those with partial response than those with complete response (180.722 ± 55.908, 161.310 ± 56.339, 84.810± 41.389, respectively, overall P = < 0.001). Clusterin was a useful marker in detecting HCC with 73.33% sensitivity and 75% specificity at a cutoff of ≥ 86.6 mg/L, and it also had 95.24% sensitivity and 77.78% specificity in detecting tumor progression at a cutoff of ≥ 146.6 mg/L, according to the mRECIST scoring system. In conclusion, clusterin may be a helpful diagnostic and prognostic marker for HCC after locoregional treatment, as its baseline level is useful in predicting response and progression of HCC in correlation with the mRECIST scoring system.