The Potential Role of Circulating Long Miscellaneous RNAs in the Diagnosis and Prognosis of Hepatitis C Related Hepatocellular Carcinoma.

Ribonucleic acids (RNAs) are important regulators of gene expression and crucial for the progression of hepatocellular carcinoma (HCC). This study was designed to determine the diagnostic and prognostic utility of the circulating long miscellaneous RNAs; LINC01419, AK021443, and AF070632 in HCV-related HCC patients. Real-time PCR was used to measure their relative expression levels in the plasma of 194 HCV patients, 120 HCV-related HCC patients and 120 healthy controls. LINC01419 and AK021443 expression levels had significantly increasing linear trend estimates while AF070632 was dramatically downregulated in HCC compared to HCV. Interestingly, LINC01419 and AK021443 served as more significant diagnostic biomarkers for HCC than AF070632 and AFP. Multivariate analysis with cox regression revealed that the high expression of AK021443 [HR = 10.06, CI95%: 3.36-30.07], the high expression of LINC01419 [HR 4.13, CI95%: 1.32-12.86], and the low expression of AF070632 [HR = 2.70, CI95%: 1.07-6.81] were significant potential prognostic factors for HCC. Besides, the Kaplan-Meier analysis showed that HCC patients with high LIN01419 and AK021443 and low AF070632 expression levels had shorter OS. The circulating LINC01419 and AK021443 can be used as noninvasive potential biomarkers for diagnosis and prognosis of HCV-related HCC patients than AF070632 providing new targets for limiting the progression of the disease.

Effects of direct acting antiviral therapy on liver stiffness measured by using fibro scan in Egyptian patients with chronic hepatitis C.

Aim Egypt has the highest incidence of hepatitis C virus (HCV) infection in the world. Fibrosis development is common in HCV cases, and it is important in disease prediction. The aim of this study was to demonstrate the role of fibro scan in assessment of changes in hepatic stiffness in patients with chronic HCV infection following direct acting antiviral treatment (DAAT). Methods This prospective observational research included 120 patients with compensated HCV infection. All patients were subjected to fibro scan before and after receiving DAAT. Patients' history, clinical examination, laboratory parameters (red - RBCs, and white blood cells - WBCs, hepatic function test, renal function test, coagulation profile, HBsAg, AFP - alpha feto protein, HbA1C, HCVAb) and fibro scan were done for all patients. Results Stiffness may differentiate F0-2 minimal fibrosis from F3-4 massive fibrosis using ROC-curve analysis, with 77.5% sensitivity, 90% specificity, 88.57% positive predictive value (PPV), and 80% negative predictive value (NPV). With sensitivity, specificity, PPV, and NPV of 71.4%, 44.5%, 43.48%, and 71.43%, respectively, the APRI-score can discriminate F0-2 from F3-4 at cutoff of 0.314. At a cutoff of 1.18, Fib4 calculation can discriminate F0-2 from F3-4, with sensitivity, specificity, PPV, and NPV of 78.6%, 64.1%, 63.04%, and 78.57%, respectively. Conclusion Hepatic fibrosis measurements such as fibro scan and non-invasive fibrosis scores (FIB-4) and aspartate aminotransferase (AST) to platelet ratio index (APRI) showed a significant improvement after direct-acting antiviral therapy. Improvements in hepatic function tests, serum creatinine level, and platelet count are also seen.

Genetic polymorphism of fibroblast growth factor receptor 2 and trinucleotide repeat-containing 9 influence the susceptibility to HCV-induced hepatocellular carcinoma.

BACKGROUND: Fibroblast growth factor receptor 2 (FGFR2) and trinucleotide repeat-containing 9 (TRNC9) gene polymorphisms have been associated with some cancers. We aimed to assess the association of FGFR2 rs2981582 and TRNC9 rs12443621 polymorphisms with hepatocellular cancer risk. METHODS: One hundred patients with HCV-induced HCC, 100 patients with chronic HCV infection, and 100 controls were genotyped for FGFR2 rs2981582 and TNRC9 rs12443621 using allele-specific Real-Time PCR analysis. RESULTS: FGFR2 rs2981582 genotype TT was associated with increased risk of HCC when compared to controls (OR = 3.09, 95% CI = 1.24-7.68). However, it was significantly associated with a lower risk of HCC when using HCV patients as controls (OR = 0.21, 95% CI = 0.09-0.5), and T-allele of FGFR2 appears to be a protective allele against HCC in HCV patients (OR = 0.42, 95% CI = 0.21-0.85). While AG and GG genotypes of TNRC9 rs12443621 were linked with significantly increased risk of HCC (OR = 3.91, 95% CI = 2.02-7.6 and OR = 9.26, 95% CI = 3.21-26.7 respectively) and HCV patients carrying G allele were at increased risk of HCC by 2.7-fold. A significant high frequency of small tumor size and early-stage of HCC were observed in patients carrying FGFR2 rs2981582 genotype CT and TT (P = 0.029 and <0.001 respectively), while, TNRC9 rs12443621 genotype AG and GG were associated large tumor size and late-stage of HCC (P < 0.001 and 0.015 respectively). CONCLUSIONS: SNPs in rs2981582 for FGFR2 and rs12443621 for TNRC9 gene were associated with HCC susceptibility, suggesting their implication in hepatocarcinogenesis in chronically HCV-infected patients.