RECK gene polymorphisms in hepatitis B-related hepatocellular carcinoma: A case-control study.

BACKGROUND AND STUDY AIMS: Chronic hepatitis B (CHB) infection is a major risk factor for hepatocellular carcinoma (HCC). The RECK gene is a critical tumor suppressor gene. This study aimed to assess the association between RECK gene single nucleotide polymorphisms (SNPs) and the development of HCC in Egyptian patients with chronic hepatitis B. PATIENTS AND METHOD: In this case-control study, we enrolled patients with CHB from the Gastroenterology Department, Benha University, from June 2016 to February 2018. The RECK gene SNP rs10814325 was identified using real-time PCR allelic discrimination via TaqMan SNP genotyping assays (Applied Biosystems, USA). RESULTS: We enrolled 140 participants in this study. The participants were divided into Group I, which comprised 50 participants with CHB only, Group II, which comprised 50 participants with CHB and HCC, and Group III, which comprised 40 healthy participants. A significantly higher hepatitis B virus DNA viremia level was found in patients with HCC. The predominant RECK genotype was the T/T allele, followed by the T/C allele; however, no significant difference in the distribution of RECK gene SNPs was found between the study groups. No statistically significant difference in RECK gene SNPs was reported among patients with HCC of different Child classes or based on the number, site, size of HCC, and lymph node involvement. Receiver operating characteristic curves showed that a serum alpha-fetoprotein level of 92 ng/ml was 96 % sensitive and 100 % specific for the detection of HCC, with an area under the operating characteristic curve of 0.98. CONCLUSION: RECK gene SNPs have no significant association with the development and characteristics of hepatitis B-related HCC in Egyptian patients.

Evaluation of liver steatosis, measured by controlled attenuation parameter, in patients with hepatitis C-induced advanced liver fibrosis and hepatocellular carcinoma.

INTRODUCTION: Steatosis is a documented feature of chronic hepatitis C (CHC). There is an association between steatosis decrease and fibrosis progression. The association between steatosis and advanced fibrosis versus hepatocellular carcinoma (HCC) development has not been precisely evaluated. The controlled attenuation parameter (CAP) was applied as an immediate and efficient process to detect and quantify hepatic steatosis with adequate accuracy. AIMS: The aim of this study was to assess the difference in liver steatosis between patients with hepatitis C virus-related advanced hepatic fibrosis versus HCC. PATIENTS AND METHODS: This cross-sectional study included 130 patients with HCC, attending the multidisciplinary HCC clinic, Cairo University, and 54 patients with CHC between October 2015 and June 2016. Clinical and laboratory characteristics were recorded. Liver stiffness and CAP were obtained by using the FibroScan 502, touch. RESULTS: All included patients had genotype 4. The mean CAP value was significantly lower in HCC (209.5±57.1 dB/m) versus CHC (259.9±54.9 dB/m). Receiver operating characteristic curve revealed an area under the curve of 0.75 for the differentiation between groups. At a cutoff value of 237 dB/m, sensitivity was 72.3%, specificity was 70.7%, positive likelihood ratio was 2.5, and negative likelihood ratio was 0.4 in the differentiation between CHC versus HCC. Logistic regression analysis revealed an odds ratio of 6.4 for the diagnosis of HCC with CAP of less than 237 dB/m. Multivariate analysis, controlling for age, sex, BMI, triglycerides, and cholesterol levels, revealed a significantly increased odds for HCC diagnosis (odds ratio: 4.3, P=0.006). CONCLUSION: The progression of CHC is associated with a decrease in steatosis, particularly toward advanced fibrosis and HCC. Steatosis reduction less than 237 dB/m is likely to be associated with HCC.

Interleukin-18 and its gene single nucleotide polymorphisms (SNPs) influence chronic hepatitis C progression.

INTRODUCTION: Interleukin-18 (IL-18) is a pro-inflammatory cytokine that is induced by hepatitis C virus (HCV) infection. Inter-individual variations of IL-18 gene expression may alter HCV-associated liver injury. Variable single nucleotide polymorphisms (SNPs) have been detected within IL-18 gene sequence. Quantitative assessment of IL-18 plasma level and detection of genotype frequencies of 2 functional polymorphisms of its gene (-607 C/A and -137 G/C) were done to assess their impact on the severity of chronic hepatitis C (CHC). METHODOLOGY: Cases group (I) comprised 110 treatment naïve CHC Egyptian patients (78 Males and 32 Females, mean age = 40.7 ± 11.8 years) who underwent routine laboratory investigations. Assessment of plasma level of IL-18 was done by enzyme-linked immunosorbent assay (ELISA), detection of IL-18 gene polymorphisms at positions -607 C/A and -137 G/C by polymerase chain reaction sequence specific polymorphism (PCR-SSP) analysis and Liver biopsy with METAVIR scoring were done. The control group (II) comprised 90 healthy participants. RESULTS: Plasma levels of IL-18 were significantly higher in cases than the control group. We found a statistically highly significant (p < 0.001) positive correlation between IL-18 plasma level and both METAVIR necro-inflammatory grade and fibrosis stage. The A/A allele at -607 position was significantly more frequent (p < 0.05) in patients with F ≤ 1. CONCLUSIONS: Higher IL-18 plasma levels are found in CHC patients and positively correlate with the severity of liver disease. The presence of A/A allele at -607 position of IL-18 gene promoter is associated with milder liver disease.

Clinical significance of vascular endothelial growth factor in hepatitis C related hepatocellular carcinoma in Egyptian patients.

BACKGROUND AND AIMS: Several angiogenic factors are involved in the development and progression of hepatocellular carcinoma (HCC), a hypervascular tumor. Vascular endothelial growth factor (VEGF) is a primary driving force for angiogenesis, and its overexpression has been reported in HCC. However, the significance of plasma and tissue VEGF levels in HCC in Egyptian patients with chronic hepatitis C (CHC) infection is understudied. The aim of this study was to evaluate the role of VEGF (measured in plasma and liver tissue) in patients with hepatitis C virus-related HCC and to assess its significance in the diagnosis and prognosis of HCC. MATERIALS AND METHODS: A total of 90 subjects were studied. Among 90 subjects, 60 with CHC were examined and were subdivided into two groups: 30 patients with CHC-related HCC (HCC group) and 30 patients with CHC without HCC (non-HCC group). Thirty apparently healthy subjects served as the control group. VEGF was estimated in plasma by enzyme-linked immunosorbent assay and its expression in liver tissue was evaluated by real-time polymerase chain reaction. VEGF expression level and its relationship to tumor parameters, patients' liver function profile, and patients' clinical parameters were also investigated. RESULTS: Plasma VEGF levels in the HCC group were significantly higher than those of the non-HCC group, and both groups had significantly higher plasma VEGF levels than did the control group. Liver tissue VEGF expression was significantly higher in the HCC group than in the non-HCC group and positively correlated with plasma VEGF in the HCC group. The plasma VEGF levels were positively correlated with patients' age, aspartate aminotransferase levels, serum alpha-fetoprotein levels, the presence of portal vein thrombosis, and the number of hepatic focal lesions in the HCC group. However, plasma VEGF levels were not significantly correlated with the Child-Pugh score, alanine aminotransferase levels, the size of focal lesions, and Okuda stage. Using both the VEGF and alpha-fetoprotein levels to detect HCC maximizes the sensitivity and specificity. CONCLUSION: Plasma levels of VEGF may be a useful diagnostic and prognostic marker for HCC in patients who have been diagnosed with CHC.