No abstract

NOD-like receptor pyrin domain containing 3 (NLRP3) is a microbial and danger signal sensor that acts as a regulator of inflammation via activation of Caspase-1 (CASP1) and has been identified as a major contributor to human liver diseases. The present study was conducted to investigate the association between NLRP3 and the progression of hepatitis C virus (HCV)-related liver disease. Serum NLRP3 levels were analyzed in 49 patients with chronic HCV infection and 18 healthy controls and liver tissues from 34 patients were examined to assess the protein expression of NLRP3 and its activation marker CASP1 using immunohistochemical staining. The results showed that the median serum NLRP3 levels was significantly higher in HCV-infected patients compared with healthy controls (1040 pg/ml vs 695 pg/ml respectively, P < 0.001) and were positively correlated with hepatic NLRP3 and CASP1 expression (r = 0.749, P < 0.001 and r = 0.557, P = 0.001 respectively). The NLRP3 levels in serum and the liver significantly increased with worsening liver pathology and showed positive correlations with serum aminotransferases levels, HCV viremia, and albumin-bilirubin score (P < 0.05). The receiver operating characteristic curve analysis revealed a high diagnostic performance of serum NLRP3 in determining the extent of liver necroinflammation, fibrosis, and steatosis (area under the curve = 0.951, 0.971, and 0.917 respectively, P < 0.001). In conclusion, NLRP3 plays an important role in liver disease progression during HCV infection via CASP1 activation and might be a promising therapeutic target. Serum NLRP3 could be an additional biomarker for liver inflammation and fibrosis.

Aim of the study: Homeobox transcript antisense intergenic RNA (HOTAIR) is a long non-coding RNA classified as an oncogene and has been implicated in liver cancer initiation and progression. This study investigated the clinical usefulness of serum HOTAIR to predict hepatocellular carcinoma (HCC) and prefigure the tumor stage. Material and methods: This study included 80 patients with de novo HCC divided into 40 late-stage HCC patients (group IA) and 40 early-stage HCC patients (group IB), 40 patients with non-tumorous liver cirrhosis (group II), and 20 healthy controls (group III). Serum HOTAIR was measured using real-time quantitative polymerase chain reaction. Serum α-fetoprotein (AFP) was measured via enzyme-linked immunosorbent assay. Results: Serum HOTAIR was significantly higher in groups IA, IB and II compared to healthy subjects. Serum HOTAIR was significantly higher in group IA than group IB, and in groups IA and IB compared to group II. Serum HOTAIR at cut-off value > 15.45 (AUC = 0.71) showed 66% sensitivity and 78% specificity in discriminating HCC patients of group IB from HCC patients of group IA. When combined with AFP, the discriminative sensitivity and specificity increased to 74% and 90% respectively (AUC = 0.85). Serum HOTAIR at cut-off value > 9.42 (AUC = 0.823) showed 67.5% sensitivity and 93.3% specificity in discriminating HCC patients of group IB from patients with non-tumorous cirrhotic liver. When combined with AFP, the discriminative sensitivity and specificity increased to 80% and 98.3% respectively (AUC = 0.954). Conclusions: Circulating HOTAIR is a potential biomarker which may be used solely, or preferably in combination with AFP, to help HCC detection in cirrhotic liver and prefigure the tumor stage.

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Aim of the study: Portal vein thrombosis (PVT) is a well-known consequence of cirrhosis. Its pathophysiology is complex, with possible downstream hepatic decompensation. This study was conducted to describe the changes of protein C (PC), protein S (PS) and D-dimer blood levels associated with PVT formation in cirrhosis and the relation to the degree of liver dysfunction. Material and methods: This was a case-control study that included 50 cirrhotic patients who presented with acute de novo non-malignant PVT and 50 cirrhotic patients without PVT as a control group. The severity of liver disease was classified as per the Child-Turcotte-Pugh (CTP) score. Doppler ultrasonography identified acute portal vein occlusion, and dynamic contrast-enhanced computed tomography confirmed the extent and nature of PVT. Blood PC, PS and D-dimer levels were measured using enzyme-linked immunosorbent assay. Results: PC and PS levels were significantly lower, and the D-dimer level was significantly higher, in cirrhotic patients with PVT compared to the control group. PC and PS levels were significantly decreased in patients with higher CTP score of both groups. The D-dimer level did not vary significantly with the degree of liver dysfunction in patients of either group. PC, PS and D-dimer at the cut-off points of ≤ 77 IU/dl, ≤ 63 IU/dl, and > 300 ng/ml, respectively, significantly suggested PVT occurrence. Conclusions: Alteration of the anticoagulant proteins and D-dimer contributed to PVT formation in cirrhotic patients and could help stratify the degree of liver dysfunction. Blood level of these hemostatic proteins could be incorporated into a probability score for early diagnosis and treatment of PVT in cirrhosis.