• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.637-642
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• 2014

The pathogenesis of hepatocellular carcinoma (HCC) related to habitual betel quid (BQ) chewing is unclear. Risk of HCCis increased with adverse hepatic fibrosis. This study aimed to assess the impact of chronic viral hepatitis on adverse hepatic fibrosis in HCC related to BQ chewing. This hospital-based case-control study enrolled 200 pairs of age- and gender-matched patients with HCC and unrelated healthy controls. Serologic hepatitis B surface antigen (HBsAg), antibodies to hepatitis C virus (anti-HCV), ${\alpha}$-fetoprotein (AFP), and surrogate markers for significant hepatic fibrosis were measured. Information on substance-use habits was obtained with a questionnaire. By analysis of surrogate markers for hepatic fibrosis, the prevalence of significant hepatic fibrosis in patients chewing BQ was between 45.8% and 91.7%, whereas that for patients without BQ chewing was between 18.4% and 57.9%. The difference was significant (P <0.05 for each surrogate marker). Multivariate analysis indicated that cirrhosis with Child-Pugh C (odds ratio (OR) = 3.28; 95% confidence interval (CI), 1.29-8.37), thrombocytopenia (OR = 3.92, 95% CI, 1.77-8.68), AFP >400 mg/L (OR = 2.21, 95% CI, 1.05-4.66) and male gender (OR = 4.06, 95% CI, 1.29-12.77) were independent factors associated with habitual BQ chewing. In conclusion, adverse hepatic fibrosis and severe liver damage play important roles in the pathogenesis of BQ-related HCC, which could be aggravated by chronic hepatitis B and hepatitis C. BQ-cessation programs and prevention of chronic HBV/HCV infection are needed to prevent HCC related to BQ chewing.

• Journal of Trauma and Injury
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• v.28 no.1
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• pp.9-14
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• 2015

Purpose: The aim of this study was to estimate the seropositive prevalence of blood-borne infection in neurotrauma patients who underwent emergent surgical intervention, especially patients with hepatitis B virus (HBV), hepatitis C virus (HCV), syphilis and human immunodefIciency virus (HIV). Methods: A retrospective review identified 559 patients with traumatic brain injury and spinal trauma who underwent emergent surgery between 2007 and 2014. We reviewed the medical records and extracted data, including age, sex, location of lesion, result of serologic tests, time interval of admission and surgery after presenting to emergency room. Serologic tests for HBV, HCV, syphilis and HIV were performed and analyzed to determine whether the seropositive results were confirmed by the surgeon before surgery. Results: The majority of the patients were male (74.6%), and the mean age was $55.4{\pm}20.2years$. Most patients underwent surgery due to traumatic brain injury (90.0%). Fifty-three patients (10.0%) showed a positive result on at least one serologic test. Seropositive rates according to pathogens were 0.5% for syphilis, 5.2% for HBV and 3.9% for HCV. No positive results were noted on the serologic tests for HIV. HBV in patients with spinal cord injury and age from 40 to 49 years were associated with high serologic positive rate, and that result was statistically significant. However, no statistically significant differences were found in the other variables. Serologic results could not confirmed before surgery in the majority of the cases (62.1%), and 10.4% of these patients showed seropositive results. Conclusion: The results of this study emphasize the importance of taking precautions and conducting rapid serologic testing in preventing the occupational transmission of blood-borne viruses to health-care workers.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.1
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• pp.381-385
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• 2015

Background:Hepatocellular carcinoma (HCC) is the second most common malignancy in Egypt. Data mining is a method of predictive analysis which can explore tremendous volumes of information to discover hidden patterns and relationships. Our aim here was to develop a non-invasive algorithm for prediction of HCC. Such an algorithm should be economical, reliable, easy to apply and acceptable by domain experts. Methods: This cross-sectional study enrolled 315 patients with hepatitis C virus (HCV) related chronic liver disease (CLD); 135 HCC, 116 cirrhotic patients without HCC and 64 patients with chronic hepatitis C. Using data mining analysis, we constructed a decision tree learning algorithm to predict HCC. Results: The decision tree algorithm was able to predict HCC with recall (sensitivity) of 83.5% and precession (specificity) of 83.3% using only routine data. The correctly classified instances were 259 (82.2%), and the incorrectly classified instances were 56 (17.8%). Out of 29 attributes, serum alpha fetoprotein (AFP), with an optimal cutoff value of ${\geq}50.3ng/ml$ was selected as the best predictor of HCC. To a lesser extent, male sex, presence of cirrhosis, AST>64U/L, and ascites were variables associated with HCC. Conclusion: Data mining analysis allows discovery of hidden patterns and enables the development of models to predict HCC, utilizing routine data as an alternative to CT and liver biopsy. This study has highlighted a new cutoff for AFP (${\geq}50.3ng/ml$). Presence of a score of >2 risk variables (out of 5) can successfully predict HCC with a sensitivity of 96% and specificity of 82%.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1705-1712
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• 2016

Background: The aim of this study was to determine and evaluate the association of different viral infections, with hepatitis B and C viruses, Epstein-Barr virus, cytomegalovirus and human herpes virus-8 (HBV, HCV, EBV, CMV, HHV-8) with the risk of lymphomas (Hodgkin and non-Hodgkin) among Egyptian patients, and correlate with the histopathological staging and typing as well as the prevalence of combined infections. Materials and Methods: A total of 100 newly diagnosed lymphoma patients with 100 healthy age and sex matched normal controls were assayed for viral infection using enzyme linked immunosorbant assay (ELISA) followed by real time polymerase chain reaction (RT-PCR). Results: Our results showed a high statistical significant difference between cases and controls as regards clinical and laboratory findings (P<0.001 and=0.003). A high statistical difference was seen for the association of most viruses and lymphoma cases (p<0.001) except for positive HBs Ag, positive CMV IgG and HHV-8 (p=0.37, 0.70 and 1.0 respectively). No statistical significant difference was found between Hodgkin (HL) and non-Hodgkin (NHL) as regards viral prevalence except HCV antigen, 57.1% for HL and 26.5% for NHL (p = 0.03). Only, HBV DNA showed a high significant value among infiltrated bone marrow cases (p=0.003) and finally, a high significant association of 2 combined viral infections with infiltrated bone marrow lymphoma cases (p=0.04). Conclusions: Our results showed that infection with HBV, HCV, CMV and EBV were associated with increased risk of lymphoma among the Egyptian population. Detection of new associations between infectious agents and risk of cancer development will facilitate progress in elaboration of prophylactic measures, early diagnostic methods and, hopefully, novel therapy of malignant tumours.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.3923-3927
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• 2016

Infection with the hepatitis C virus is a major public health concern which can lead to carcinoma and liver failure. It has been shown that single nucleotide polymorphisms can affect the level of gene activity of tumor necrosis factor (TNF) which has an important role, especially in viral infections which can lead to apaptosis of infected hepatocellular cells. We investigated the impact of three possible genotypes for rs1800629 or A/G single nucleotide polymorphism located downstream of $TNF{\alpha}$ gene promoter in groups of control (n=76) and chronic hepatitis C patients (n=89) focusing on the response to treatment among sensitive and resistant groups. Genomic DNA was extracted from $500{\mu}l$ prepheral whole blood and PCR and RFLP were used to amplify the region of interest and genotyping. With statistical analyzes a p-value <0.05 was considered meaningful. There was no significant difference in distribution of possible three genotypes among healthy individuals and patients (P=0.906, OR=1.194, CI=0.063-22.790). However, the frequency of G allele was higher in patients whereas A allele was more common among healthy individuals (p<0.0001). Further studies with more samples seem to be necessary.

• Molecules and Cells
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• v.40 no.3
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• pp.202-210
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• 2017

The nonstructural protein 5A (NS5A) encoded by the human hepatitis C virus (HCV) RNA genome is a multifunctional phosphoprotein. To analyse the influence of NS5A on apoptosis, we established an Hep-NS5A cell line (HepG2 cells that stably express NS5A) and induced apoptosis using tumour necrosis factor $(TNF)-{\alpha}$. We utilised the MTT assay to detect cell viability, real-time quantitative polymerase chain reaction and Western blot to analyse gene and protein expression, and a luciferase reporter gene experiment to investigate the targeted regulatory relationship. Chromatin immunoprecipitation was used to identify the combination of $NF-{\kappa}B$ and miR-503. We found that overexpression of NS5A inhibited $TNF-{\alpha}$-induced hepatocellular apoptosis via regulating miR-503 expression. The cell viability of the $TNF-{\alpha}$ induced Hep-mock cells was significantly less than the viability of the $TNF-{\alpha}$ induced Hep-NS5A cells, which demonstrates that NS5A inhibited $TNF-{\alpha}$-induced HepG2 cell apoptosis. Under $TNF-{\alpha}$ treatment, miR-503 expression was decreased and cell viability and B-cell lymphoma 2 (bcl-2) expression were increased in the Hep-NS5A cells. Moreover, the luciferase reporter gene experiment verified that bcl-2 was a direct target of miR-503, NS5A inhibited $TNF{\alpha}$-induced $NF-{\kappa}B$ activation and $NF-{\kappa}B$ regulated miR-503 transcription by combining with the miR-503 promoter. After the Hep-NS5A cells were transfected with miR-503 mimics, the data indicated that the mimics could reverse $TNF-{\alpha}$-induced cell apoptosis and blc-2 expression. Collectively, our findings suggest a possible molecular mechanism that may contribute to HCV treatment in which NS5A inhibits $NF-{\kappa}B$ activation to decrease miR-503 expression and increase bcl-2 expression, which leads to a decrease in hepatocellular apoptosis.

• Journal of agricultural medicine and community health
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• v.41 no.4
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• pp.205-216
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• 2016

Objectives: We compared the difference of lipid, insulin resistance and metabolic markers based on HCV RNA in Korean adults.Methods: This was a cross-sectional study of 222 subjects visited the health promotion center of Pusan nationaluniversity hospital from 2004 to 2007. Subjects were anti-HCV antibody positive and were performed RT-PCR for HCV RNA. The HCV RNA (+) group were 85 subjects, HCV RNA (-) control group were 115 subjects, and the HCV RNA (-) but past positive group were 22 subjects. We performed anthropometry, anti-HCV, RT-PCR, plasma concentrations of insulin, total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglyceride.Results: BMI, waist circumference, blood pressure, fasting plasma glucose, triglyceride, HDL cholesterol, insulin resistance such as HOMA-IR and QUICKI were not significantly different between HCV RNA positive and negative groups. The serum total cholesterol and LDL cholesterol level were significantly lower in the HCV RNA positive group than in the negative group ($186.24{\pm}37.63$ vs $197.22{\pm}37.23$ mg/dl, p=0.041, $111.66{\pm}34.06$ vs $121.38{\pm}35.50$ mg/dl, p=0.042). After adjusting age and sex, high total cholesterol (${\geq}200mg/dl$) (adjusted OR=0.51, 95%CI 0.28-0.94, p=0.03) and high LDL cholesterol (${\geq}130mg/dl$) (adjusted OR=0.46, 95%CI 0.24~0.87, p=0.02) were inversely associated with being HCV RNA positive (p<0.05). Conclusion: The serum total cholesterol and LDL-cholesterol level were significantly lower in HCV RNA (+) group than in HCV RNA (-) group, but not in HCV RNA (-) but past positive group. Prospective cohort studies are needed to clarify the relationship between HCV RNA and metabolic markers.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.3697-3703
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• 2016

Hepatocellular carcinoma (HCC) is the most frequent type of malignant liver tumor and a high impact health problem worldwide. The prevalence of HCC is particularly high in many Asian and African countries. Some HCC patients have no symptoms prior to diagnosis and many of them therefore present at late stage and have a grave prognosis. The well-established causes of HCC are chronic hepatitis B virus (HBV) or chronic hepatitis C virus (HCV) infection or alcoholic cirrhosis and nonalcoholic steatohepatitis. The Barcelona Clinic Liver Cancer (BCLC) Staging System remains the most widely used for HCC management guidelines. To date, the treatments for HCC are still very challenging for physicians due to limited resources in many parts of the world, but many options of management have been proposed, including hepatic resection, liver transplantation, ablative therapy, chemoembolization, sorafnib and best supportive care. This review article describes the current evidence-based management of HCC with focus on early to advance stages that impact on patient overall survival.

• IMMUNE NETWORK
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• v.5 no.1
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• pp.1-10
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• 2005

Background: Chronic infection with hepatitis B virus (HBV) affects about 350 million people worldwide, which have a high risk of development of cirrhosis and hepatocellular carcinoma. Treatment of chronic HBV infection relies on IFN-${\alpha}$ or lamivudine. However, interferon-${\alpha}$ is effective in only about 30% of patients. Also, the occurrence of escape mutations limits the usage of lamivudine. Therefore, the development and evaluation of new compounds or approaches are urgent. Methods: We comparatively evaluated DNA and adenoviral vaccines expressing HBV antigens, either alone or in combined regimens, for their ability to elicit Th1-type immune responses in Balb / c mice which are believed to be suited to resolve HBV infection. The vaccines were tested with or without a genetically engineered IL-12 (mIL-12 N220L) which was shown to enhance sustained Th1-type immune responses in HCV E2 DNA vaccine. Results: Considering the Th1-type cytokine secretion and the IgG2a titers, the strongest Th1-type immune response was elicited by the DNA prime-adenovirus boost regimen in the presence of mIL-12 N220L. In addition, the codelivery of mIL-12 N220L modulated differentially the immune responses by different vaccination regimens. Conclusion: Our results suggest that the DNA prime-adenovirus boost regimen in the presence of mIL-12 N220L may be the best candidate for HBV vaccine therapy of the regimens tested in this study and will be worthwhile being evaluated in chronic HBV patients.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3741-3745
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• 2012

Background: Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the most common form of liver cancer. However, while it is associated frequently with hepatitis C virus (HCV) there is only an elementary understanding of its molecular pathogenesis. Methods: To gain insight into the molecular mechanisms of HCV-induced hepatocarcinogenesis, we performed microarray analysis on 75 surgical liver samples from 48 HCV-infected patients. Results: There were 395 differentially expressed geness between cirrhotic samples and HCC samples. Of these, 125 genes were up-regulated and 270 genes were down-regulated. We performed pathway enrichment analysis and screened as described previously. Conclusions: The differentially expressed genes might be involved in hepatocarcinogenesis through upregulating the pathways of ECM-receptor interaction, focal adhesion, cell adhesion molecules and other cancer-related pathways, and downregulating the pathways of "complement and coagulation cascades". We hope our results could aid in seeking of therapeutic targets for HCV-induced hepatocellular carcinoma.