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Background: The severity of chronic hepatitis C and susceptibility to hepatocellular carcinoma (HCC) are associated with genetic variations within vitamin D receptor (VDR) in several populations. This study aims to determine the significance of the VDRs (rs2228570, rs3782905, rs11568820) and DBP (rs7041) for the susceptibility to HCC in Egyptian patients with chronic HCV infection and their effect on the progression of liver cirrhosis to carcinogenesis. Methods: Single nucleotide polymorphisms (SNPs) VDR (rs2228570, rs3782905), and DBP rs7041 were genotyped using restriction fragment length-PCR (RFLP-PCR) technique and VDR rs11568820 was genotyped using single strand polymorphism PCR (SSP PCR). These SNPs genotypes, haplotypes and linkage disequilibrium analyses were examined in 299 Egyptian individuals (100 HCV-cirrhotic patients, 99 HCC- HCV patients, and 100 healthy controls). Result: The VDR rs2228570 CC genotype, VDR rs3782905 GC and CC genotypes, and DBP rs7041 GG genotype are significantly higher in HCC. It is noteworthy that, VDR rs3782905 CC and DBP rs7041 TG genotypes are higher in HCV induced liver cirrhosis than with HCC progression in HCV infected patients. Furthermore, among patients, the relationship between these SNPs and smoking status, gender, and HCC susceptibility was reported. Conclusion: Among the four investigated SNPs, there are associations between VDR rs3782905 and DBP rs7041 and the HCC progression in Egyptian patients chronically infected with HCV. These SNPs are considered as risk factors in HCV induced liver cirrhosis and HCC. The combinations of these SNPs with smoking status and gender are statistically linked to a high risk of HCC. Future research with a larger sample size of subjects with HCV infection is advised, because chronic liver disease induced by HCV infection is the primary cause of HCC in Egypt. We recommend screening of these SNPs for prediction of LC and HCC development in HCV infected patients, which may improve the used therapeutic protocol. These results suggest that VDR polymorphisms may be potential determinants for HCC susceptibility in Egyptian HCV patients. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the sixth most common type of cancer worldwide and fourth in Egypt. Liquid biopsy is important to get cell-tumour DNA (ctDNA), for subsequent utilisation as a biomarker for cancer diagnosis, prognosis, and treatment. In clinical oncology, ctDNA analysis is utilised in cancer screening. The collected 48 blood samples from HCC patients were classified according to Barcelona Clinic Liver Cancer (BCLC) staging, in addition to Hepatitis C Virus (HCV) group and normal group. After the liquid biopsy, ctDNA and genomic DNA (gDNA) of the same individual were extracted. Next-generation sequencing (NGS) was conducted using a Hot spot panel, and data analysis via different cancer databases was performed. There were no significant differences in the detected mutation frequency between groups. The frequency of mutations was higher in ctDNA than in the gDNA samples from the same patients. Hence, it can be concluded that these mutations are somatic mutations, rather than germline mutations. Screening of the targeted genes such as c-MET for potential mutations is very important in the determination of the appropriate therapy. Therefore, it can be used as a biomarker in the prognosis of HCC. Such screenings are also of paramount importance in the development of personalised medicine. [ABSTRACT FROM AUTHOR]

Background: In terms of cancer mortality rates, hepatocellular carcinoma (HCC) ranks third. Direct-acting antiviral drugs (DAAs) had a profound impact on the treatment of hepatitis C virus (HCV). Objective: Understanding HCC frequency among cured HCV cases and to evaluate direct acting antiviral agents (DAAs) impact on occurrence of hepatocellular carcinoma among chronic hepatitis C patients who received these drugs. Subjects and methods: In a retrospective cross-sectional study we carried out this trial in Hepatitis Viruses' Treatment Unit, El-Ahrar Teaching Hospital, Egypt on 415 patients who received direct acting antiviral agents (DAAs) for treating chronic hepatitis C virus and achieved sustained virological response (SVR) between 2017 to 2022 where all file of cases fulfilled the inclusion as well as exclusion criteria. Result: HCC was significant in older age, male, DM, HTN and patient from rural residence. Platelet and albumin significantly decreased after HCC, but alpha fetoprotein, bilirubin, ALT, AST, serum creatinine and APRI score significantly increased after HCC. Conclusion: The incidence of HCC is highest among those who already have cirrhosis, and chronic hepatitis C is the leading risk factor of this condition. Direct anti-viral agents (DAAs) may play role in occurrence of hepatocellular carcinoma (HCC) in chronic hepatitis C patients who achieved sustained virological response (SVR). [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma represents 85%—90% of primary liver tumors; it represents the 2nd leading cause of cancer-related death all over the world. There is a growing incidence of HCC worldwide and similarly, the incidence of HCC has almost doubled over the last decade in Egypt. Aim of the work: To assess clinico-epidemiological character of HCC in the last two decades and to compare between the first and second decade regarding these characters. Patients and methods: This retrospective study included 497 HCC patients' data collected from Clinical Oncology and Nuclear Medicine Department from 1999 to 2019, HCC patients were classified into 1st decade (from 1999 to 2009) and 2nd decade (2010 – 2019). Diagnosis of HCC was based on clinical, laboratory, (AFP), and radiological examinations (The abdominal US and triphasic CT scan). Results: The study revealed that the average age of HCC cases was 57 years, the majority of these were males (88%), residents in rural areas (70%), about one-fourth of them, were smokers (26.4%), DM was present in 14% of these while only 7% were hypertension. Thirty presents (30%) of them were represented by ascites and (20%) by hepatic encephalopathy of different grades. The majority of HCC patients (92.2%) have HCV Abs positive. HBS Ag was positive in 2.4% while mixed infection (HCV Abs + ve and HBS Ag + ve) was in 2% of patients only. The median level of AFP was 300 ng/ml. The severity of underlying chronic liver disease was assessed by the Child–Pugh score the mean score was 7.5 (from 6–11) and the MELD score (the mean score was 18.8 (from 6–29). Regarding tumor characteristics, HCC mass was located in the Right lobe of the liver in (63.8%), in the left lobe in (26.6%) and both lobes were affected in 9.6%. A single focal hepatic lesion was detected in about 60% of patients, 3 focal lesions in about 20%, and two focal lesions or multifocal HCC in the remaining percent. The median size of the largest tumor's diameter was 5 cm by the US and 5.3 cm by the triphasic CT. PVT, vascular invasion, LN, and distant metastasis were detected in (35.6%), (40%), (40%) and (54%) of patients respectively. In less than one-third of HCC cases, the tumors were within Milan criteria (30%). Conclusion: The 1st decade showed a significantly higher frequency of patients presented with marked splenomegaly and splenectomy, while the second decade showed a significantly higher frequency in patients who reside in rural areas. Higher frequency of DM, advanced hepatic encephalopathy grade III/ IV, and unfortunately more aggressive tumors with PVT, vascular invasion, LN metastasis, and distant metastasis were detected in the 2nd decade. [ABSTRACT FROM AUTHOR]

Aim of the study: To evaluate the role of MIF gene polymorphism rs755622 G>C in occurrence and progression of hepatocellular carcinoma (HCC) among a cohort of Egyptian patients. Material and methods: This case-control study was conducted on 50 patients with HCC after chronic viral hepatitis and 50 healthy volunteers, recruited between July 2021 and January 2022. All patients with HCC were evaluated for severity of liver disease using a Child-Pugh score, and TNM and BCLC scoring systems. MIF 173 G>C (rs755622) single nucleotide polymorphism was performed for all participants by polymerase chain reaction using restriction fragment length polymorphism technique (RFLP-PCR). Results: Overall results showed significantly higher frequencies of GG (wild homozygous genotype) and mutant heterozygous genotype GC and G allele (OR = 6.303, 95% CI: 3.374-11.775) among patients with HCC compared to the control group (p = 0.001) for all. Also, significantly higher frequency of genotype GG was detected among patients with advanced Child scores (B and C) (p = 0.039) and TNM stages (III and IV) (p = 0.013). There was significantly higher frequency of the G allele among patients with multiple hepatic focal lesions compared to those with a single focal lesion (p = 0.01). Conclusions: An obvious role of MIF (rs755622) gene polymorphism could have an important role in susceptibility and progression of HCC among patients with chronic viral hepatitis induced liver cirrhosis. [ABSTRACT FROM AUTHOR]

Background: Chronic hepatitis C (HCV) infection is implicated in hepatocarcinogenesis. Hepatocellular carcinoma (HCC) progression is influenced by a number of genetic and epigenetic mechanisms. One of the most critical variables in early hepatocarcinogenesis is the dysregulation of the epidermal growth factor receptor (EGFR) or the epidermal growth factor (EGF) signaling pathway. This study aimed to assess the association between the incidence of HCC and the EGF 61A/G polymorphism in chronic HCV Egyptian cases. Patients and methods: A comparative study was carried out with a total of 165 single ethnic Egyptian. They were classified into 3 groups: Chronic HCV (n = 55), HCC (n = 60), and healthy cases (n = 50). Genotyping was performed for all participants using RT-Multiplex PCR. Results: The frequencies of genotypes were in HCV G/A 32.7%, G/G 60.0%, and A/A 7.3%, and in HCC G/A 51.7%, G/G 30.0%, and A/A 18.3%. The control group was G/A 52.0%, G/G 20.0%, and A/A 28.0%. The alleles frequencies in HCV were G 76.4%, and A 23.6%, in HCC were G 55.8% and A 44.2%. In the control group were G 46.0% and A 54.0%. The difference regarding the genotype and allele frequency among studied groups was highly significant. The G/G genotype (P-value 0.006) were protective against HCC development. However, HCV patients with the A/G genotype (P-value 0.04) might be at a higher risk to develop HCC. Conclusion: The indications for EGF 61A/G gene polymorphism's correlation with susceptible threat for HCC development in HCV patients in Egypt. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a highly prevalent malignancy. It is a common type of cancer in Egypt due to chronic virus C infection (HCV). Currently, the frequently used lab test is serum α-fetoprotein. However, its diagnostic value is challenging due to its low sensitivity and specificity. Genetic biomarkers have recently provided new insights for cancer diagnostics. Herein, we quantified Lnc HULC and miR-122 gene expression to test their potential in diagnosis. Both biomarkers were tested in the sera of 60 HCC patients and 60 with chronic HCV using real-time RT-PCR. miR-122 was highly expressed in HCV patients with a significant difference from the HCC group (p = 0.004), which points towards its role in prognosis value as a predictor of HCC in patients with chronic HCV. HULC was more highly expressed in HCC patients than in the HCV group (p = 0.018), indicating its potential use in screening and the early diagnosis of HCC. The receiver operating characteristic (ROC) curve analysis showed their reliable sensitivity and specificity. Our results reveal that miR-122 can act as a prognostic tool for patients with chronic HCV. Furthermore, it is an early predictor of HCC. LncRNA HULC can be used as an early diagnostic tool for HCC. [ABSTRACT FROM AUTHOR]

Aim: An ineffective immune response resulting from dysregulation of cytokine production might encourage viral persistence and cause chronic viral hepatitis to worsen. This study examined the relationship between alterations in interleukin-6 (IL-6) levels and the IL-6 - 174 G > C (rs1800795) polymorphism, as well as how this polymorphism affects the development and progression of chronic hepatitis brought on by hepatitis B (HBV) and hepatitis C (HCV) into hepatocellular carcinoma (HCC)., Patients and Methods: Whole blood samples from 126 Egyptian patients with HCC (111 with HCV and 15 with HBV), as well as 126 age- and sex-matched healthy individuals, were used to extract DNA. Using PCR-based allele-specific amplification (ASA), the existence of the IL-6 G-174C polymorphism was investigated. Additionally, each participant's serum IL-6 levels were determined using an enzyme-linked immunosorbent assay (ELISA)., Results: The primary observations revealed that HCC patients had greater serum levels of IL-6 compared to the control groups (p < 0.001). Patients with the variant (CG and GG) genotype in the HCC group were found to have more disease severity indicated by higher levels of alpha-fetoprotein (AFP) and a higher ascites grade, as well as increased inflammatory activity as defined by higher levels of IL-6 and C-reactive protein (CRP) (p < 0.001 for both) in comparison to patients with the wild-type (CC) genotype (p < 0.001 and p = 0.002, respectively)., Conclusion: The rs1800795 SNP in the IL-6 gene was associated with increased inflammatory activity and high levels of IL-6, indicating that this SNP may play a role in the development of HCC in Egyptian patients with chronic viral hepatitis., (© 2024. The Author(s).)

Purpose: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Although alpha-fetoprotein (AFP) has been used for 60+ years as an HCC diagnostic serum marker, its accuracy is debated. Notably, the role of interleukin 10 (IL-10) in cancer development and metastasis is elevated in various tumor types, including HCC and chronic HCV infection. Our study aimed to investigate the diagnostic performance of IL-10 and AFP as biomarkers for HCV-induced HCC in an Egyptian population., Methods: Eighty participants were recruited and categorized into three groups: HCV-related HCC (n=40), HCV-related cirrhosis (n=40), and control (n=20).The collected blood samples were analyzed to evaluate liver function, AFP levels, and IL-10 levels., Results: Our analysis showed that AFP demonstrated low sensitivity (40% false-negative) and low specificity (33% false-positive).IL-10 levels were significantly higher (P < 0.001) in patients with HCC than in the cirrhosis and control groups. The serum AFP and IL-10 combination revealed significantly increased sensitivity (97.5%), diagnostic accuracy (71.1%), AUC (0.798), PPV (73.3%), and NPV ( 69.5%) when compared with either of them alone., Conclusion: the reliability of AFP as a major HCC marker was poor. However, IL-10 levels are a novel biomarker for the degree of HCC inflammation, considering IL-10's potential role in HCV-HCC development. We suggest combining AFP with IL-10 to improve the diagnostic and prognostic value of HCC considerably. Future research on these biomarkers should prioritize their clinical validity, prognostic usefulness, and compatibility with other therapeutic approaches as immunotherapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: Hepatocellular carcinoma (HCC) is one of the most common cancers in Egypt with fatal outcome. The molecular pathogenesis of this type of cancer is so complex involving interaction of several signaling pathways. Among those is Wingless (WNT)/β-catenin signaling pathway, which is frequently activated in HCC. Objectives: To investigate the relationship of different localization patterns of β-catenin in relation to different histopathologic parameters in Egyptian HCC cases. Patients and methods: One hundred and twenty-one (121) HCC specimens were subjected for β-catenin evaluation by immunohistochemistry. Results: The studied HCC cases showed β-catenin membranous expression in 47/121 (38.8%) of cases, while nucleocytoplasmic localization was observed in 31/121 (25.6%). Most of HCC cases that showed single tumor mass presentation exhibited negative nucleocytoplasmic expression pattern (79.2%, P=0.02). Membranous pool of β-catenin was associated with adverse prognostic factors like increased positivity among high-grade cases (P=0.04), higher H score value in cases having lymphovascular invasion, positive lymph node and higher (advanced) TMN stages (P = 0.01, 0.00, 0.00 &0.03 respectively). Conclusion: HCC cases showed heterogeneous β-catenin expression pattern. Membranous β-catenin localization was associated with aggressive prognostic parameters of HCC. [ABSTRACT FROM AUTHOR]

Chronic hepatitis C (CHC) is a worldwide etiology of chronic hepatic insult particularly in Egypt. DNA‐repair systems are responsible for maintaining genomic integrity by countering threats posed by DNA lesions. Deficiency in the repair capacity due to genetic alterations in DNA‐repair genes can lead to genomic instability and increased risk of cancer development. The present work aimed at studying the possible association between XRCC1‐G28152A (rs25487), XRCC3‐C18067T (rs861539), and XRCC7‐G6721T (rs7003908) single nucleotide polymorphisms (SNPs) and the susceptibility to hepatocellular carcinoma (HCC) in Egyptian population. The study was conducted on 100 newly diagnosed HCC patients and 100 age‐ and sex‐matched healthy controls. Laboratory workup revealed that all HCC patients have chronic hepatitis C viral infection. Genotyping of the studied SNPs was performed by real‐time PCR. The heteromutant genotype of XRCC1 (GA) conferred an almost two‐fold increased risk of HCC (OR , 2.35; 95% CI, 1.33‐4.04). Regarding XRCC7, the heteromutant (TG) genotype conferred a two‐fold increased risk of HCC (OR , 2.17; 95% CI, 1.23‐3.82). Coinheritance of the polymorphic genotypes of XRCC1 and 7 was significantly higher in HCC cases than controls and was associated with an 11‐fold increased risk of HCC (OR , 11.66; 95% CI, 2.77‐49.13). The frequency of XRCC3 polymorphic genotypes in HCC patients was close to that of the controls. [ABSTRACT FROM AUTHOR]

Background: Abnormal autocrine fibroblast growth factor 19 (FGF19) productions have been observed in several types of cancers, including hepatocellular carcinoma (HCC), which is considered 3rd cause of cancer deaths worldwide with gradually increased incidence. Objective: To investigate the role of FGF 19 in prediction, diagnosis and follow up of HCC together with alpha feto protein (αFP). Patients and methods: This study was carried in Internal Medicine Department and Clinical Pathology Department, Faculty of Medicine Zagazig University Egypt in the period from October 2017 to October 2020. The study included 150 patients (111 males and 39 females) classified into 3 groups: 50 healthy volunteers as a control, 50 patients with liver cirrhosis documented by examination and investigation and 50 Patients with HCC with variable sizes. All participants in the study were subjected for the following after written consent and approval by their search ethics committee of Zagazig University. Result: The median of FGF19 level between control, liver cirrhosis and HCC was 4, 6 and 10 87 pg/ml respectively with higher sensitivity for detection of small HCC with high significance of α Fp between HCC > cirrhosis > control. Conclusion: FGF19 can be used successfully as a novel biomarker for HCC diagnosis and follow up after treatment together with already existing biomarker α FP. [ABSTRACT FROM AUTHOR]

Background: This study was performed to investigate the expression of different biomarkers in patients with hepatocellular carcinoma and its connection with detective biomarkers. To achieve this objective, seventy subjects were examined in this study, sub-grouped to forty HCC patients and thirty HCV-affected patients with matched thirty healthy individuals. The study involved several groups of participants who were matched based on their age and gender., Methods: The expression pattern of biomarkers was monitored by quantitative polymerase chain reaction (qRT-PCR). Finally, we utilized a ROC curve to investigate the predictive accurateness of those distinct biomarkers as well as a traditional tumor marker, AFP, in detecting HCC cases., Results: The baseline biomarker expression levels were markedly greater in HCC patients than in those affected by HCV or healthy subjects. We stated that the sensitivity and the specificity of the different biomarkers alone did not improve than that of AFP alone. When comparing AFP with different biomarkers, the diagnostic validity improves only when combining with CK-1., Conclusions: Overall, our results indicate that CK-1 mRNA expression could help as a noninvasive tumor biomarker for HCC prognosis and diagnosis when combining with AFP., (© 2023. The Author(s).)

Objective: The aim of this study was to investigate the ADAM 10 rs.653765 SNP genetic polymorphism in the hepatocellular carcinoma occurrence (de novo and post DAAs)., Methods: This study was conducted on 360 participants divided to 4 groups. Group 1: 90 chronic adult patients infected with HCV received DAAs regimens and evolved HCC during the period of follow up. Group 2: Another 90 HCV patients received the same DAAs regimens and did not show HCC manifestations during the same follow up period. Group 3 included 90 de novo HCC patients (did not receive any DAAs). Finally, 90 apparently healthy participants as group 4. Clinical and laboratory data were evaluated, and ADAM 10 genotyping were performed using qPCR., Results: The study showed statistically significant between HCC de novo and HCC deterioration on top of DAAs according to three scoring systems (Child Pugh, BCLC and HKLC) with p- value <0.05. Regarding ADAM10 gene polymorphism, the study showed a significant difference between CC versus CT+TT genotypes of HCC groups according to Child Bugh, BCLC and HKLC staging systems. Yet, no significant difference was found when ADAM10 genotypes and allele frequencies were compared between the four different studied groups. No difference in the survival rate between HCC de novo and on the top of DAAs but more aggressive stages with HCC on top of DAAs., Conclusion: ADAM10 genotypes did not show any significant association with HCC. Also, no differences in the death rate recorded between the de novo HCC and HCC post DAAs treatment with statistical significant worse staging of HCC post DAAs and were noted. the study showed a significant difference between CC versus CT+TT genotypes of HCC groups according to Child Bugh, BCLC and HKLC staging systems., .

Background: Hepatitis C virus is considered to be one of the most important devastating causes of chronic hepatitis, cirrhosis, and hepatic cellular carcinoma. Toll-like receptor 7 (TLR7) is a pathogen-recognition receptor that is expressed on innate immune cells. It recognizes viral RNA which induces its activation with a subsequent increase in IFN-α transcription. It has been postulated that HCV may cause down regulation of these receptors as one of immune evading mechanisms that participate in viral persistence. The aim of the work: Was to investigate the expression of TLR7 in peripheral blood of patients with chronic HCV infections and patients with HCC, comparing it with normal individuals, and correlating it with both serum levels of IFN-α and viral load. Results: The results of this study showed a significant decrease in TLR7 expression in patients with chronic HCV and no detection at all in patients with HCC, in addition a significant negative correlation was observed between levels of TLR7 expression and interferon α when compared to viral load. Conclusion: Down regulation of TLR7 expression in HCV and HCC patients may contribute to the decrease of IFN-α and increase in viral load. These results raise the possibility that by targeting TLR7 with high affinity pharmacological stimulants may be able to control HCV infection by induction of IFN-α and direct activation of antiviral mechanisms in hepatocytes. Additionally, they provide insight about the potential use of TLR7 as a new set of molecular markers for prognosis and outcomes of chronic HCV infection and HCC. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of most frequent cancer in the world, genetic polymorphisms have been reported to play a role in susceptibility to HCC. The present study aimed to study the possible association between glutathione -- S -- transferase (GSTP1) gene polymorphism and susceptibility to HCC. The study was carried out on 120 subjects divided into 3 groups : Group (A) included 60 HCC patients and group (B) included 40 chronic hepatitis C virus patients and group (C) included 20 age and sex matched healthy control. All subjects were submitted to full history taking, liver function tests, GSTP1 gene polymorphism by PCR -- RFLP. This study found a significant difference between HCC group and each of hepatitis C virus group ( HCV) and control group, while there is no significant differences between HCV group and the control group as regarding GSTP1 genotyping with the highest percent of ile/val polymorphism (IV) and val/val polymorphism (VV) in HCC group and ile/ile (II) polymorphism among HCV and the control group. GSTP1 IV genotype frequency was associated with 5.53 times higher risk of HCC than GSTP1 II genotype, while GSTP1 VV genotype frequency was associated with 6.40 times higher risk of HCC than GSTP1 II genotype when compared to the other two groups together. The frequency of GSTP1 val (V) allele is higher in HCC when compared to the other two groups together and it was associated with 2.70 times higher risk of HCC than GSTP1 I allele. The present study reported that carriage of GSTP1 ile/val and val/val genotypes have a role in susceptibility to HCC and this susceptibility are not through the alteration of the expression of clinical pathological markers and we recommend performance of this work on a large scale to confirm these results. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most deadly cancers worldwide and it represents a major world health problem. The burden of hepatocellular carcinoma (HCC) has been increasing in Egypt with a doubling in the incidence rate in the past 10 years. . The genetic alterations that take place in the transformation of normal cells to neoplastic cells give an insight into the molecular mechanism of the disease. Glypican 3 (GPC3) is protein that plays a role in the control of cell division and growth regulation. It acts as a tumor suppressor gene in some tissues, while acting as an oncofetal protein in other tissues. The aim of this work was to study gene expression of GPC 3 in HCC patients in Egypt. This was an internally controlled case series where HCC tumor tissue and non-tumor tissue from the same patient were analyzed for the expression of GPC 3. This study showed that statistically no significant positive correlation between AFP and GPC3 was observed. So, GPC 3 may serve as a potential marker for the diagnosis and prognosis HCC. [ABSTRACT FROM AUTHOR]

Background: Hepatocarcinogenesis involves alterations in p53, Bcl-2 and human Mut S homologue-2 (hMSH2) genes. In Upper Egypt, the clinicopathologic and genetic changes during hepatocarcinogensis (cirrhotic nodules (CN); macroregenerative nodules (MRN) and dysplastic nodules (DN) are unknown. Methods: To examine these issues, 48 hepatic resection specimens entailing 25 CN, 16 MRN, 23 CN and 48 hepatocellular carcinoma (HCC) were immunohistochemically evaluated for p53, Bcl-2 and hMSH2 protein expression. Results: HCC was common in males than in females (2.6:1, P< 0.05) and with hepatitis C virus than hepatitis B virus infection (77.1% vs. 18.7%, P = 0.001). p53 expression was found in CN (3/23) and HCC (12/48). Its average weighted scores were high in DN/HCC as compared with CN (1.60 ± 0.40 and 7.20 ± 1.20, P = 0.0001). Bcl-2 expression was seen in CN, MRN, CN and HCC (7/48). Its average weighted scores were high in CN (7.60 + 1.60), HCC (6.86 + 0.85) as compared with CN (6.14 ± 0.42) and MRN (6.50 ± 0.50, P = 0.22). hMSH2 average weighted scores were reduced in HCC (7.94 ± 1.06) as compared with CN (8.47 ± 0.52), MRN (8.00 ± 1.00) and CN (8.20 ± 0.80, P>0.05). Conclusion: In Upper Egypt: (1) HCC had similar clinicopathologic features to those in the high-risk regions, and (2) alterations of the p53, Bcl-2 and hMSH2 proteins occur during hepatocarcinogensis. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and the most common cause of death in people with chronic liver diseases. In Egypt, liver cancer forms 11.75% of the malignancies of all digestive organs and 1.68% of the total malignancies. HCC constitutes 70.48% of all liver tumors among Egyptians. In the past few years, early diagnosis and advances in therapeutic measures have greatly improved the outcome of HCC patients. However, the prognosis is still poor with overall survival rates of 3-5%. The alterations in cancer driver genes and associated pathways are the major triggers for HCC. So, the identification and targeting of these genes are beneficial to understand HCC and to develop a new therapy. Aim of the work: We aimed to target CTNNB1 and RAB1A oncogenes in HepG2 cell lines by RNAi then evaluate the effect of their targeting on the viability and proliferative activity of HepG2 cells. Materials and methods: Using HepG2 cell lines, CTNNB1 & RAB1A oncogenes were targeted using two different siRNAs (small interfering RNA) for each gene. The viability of HepG2 was conducted by Trypan blue test. The cell proliferation was tested by CellTiter 96® AQueous One Solution Cell Proliferation Assay. Results: There was significant reduction in the cells’ viability detected by trypan blue test in transfected cells with siRNA targeting either CTNNB1 or RAB1A compared to Mock HepG2 cell lines (p <0.05). In addition, the proliferative activity was significantly lower in both HepG2 cell lines transfected with siRNA targeting the previous genes compared to mock cells (p<0.05). Furthermore, HepG2 cells transfected with siRNA targeting RAB1A were more proliferative compared to those transfected with siRNA targeting CTNNB1 (p <0.05). Conclusion: Targeting CTNNB1or RAB1A in HepG2 cell lines decreased the cell viability and proliferative activity. Moreover, targeting CTNNB1 was effective in decreasing cell proliferative activity compared to targeting RAB1A in HepG2 cell lines. So, targeting CTNNB1 may have a potential therapeutic effect in treatment of HCC. [ABSTRACT FROM AUTHOR]

Direct-acting antivirals (DAAs) are used for hepatitis C virus (HCV) treatment. However, treatment failure and hepatocellular carcinoma (HCC) development following treatment was reported. In this study, we assessed the role of serum vitamin D, interleukin 13 (IL-13), and microRNA-135a in the prediction of treatment failure with DAA and HCC development among Egyptian HCV-infected patients. A total of 950 patients with HCV-related chronic liver disease underwent DAA treatment. Before DAAs, serum vitamin D and IL-13 were determined by ELISA, and gene expression of miRNA-135a was assessed in serum by real-time PCR. The predictive abilities of these markers were determined using the receiver operating characteristic (ROC) curve. Sustained virological response (SVR) was achieved in 92.6% of HCV-infected patients (responders). High viral load, IL-13, miRNA-135a, and low vitamin D levels were associated with treatment failure and HCC development. HCC development was recorded in non-responders, but not in the responders (35.7% vs. 0% p < 0.001). In conclusion: serum IL-13, Vitamin D, and miRNA-135a could be potential biomarkers in monitoring DAA treatment and HCC prediction. DAAs-induced SVR may decrease the incidence of HCC.

Objective: The clinical outcomes of hepatitis C virus (HCV) infection and its sequelae including liver cirrhosis and hepatocellular carcinoma (HCC) are greatly affected by host genetic factors; however, the possible mechanisms are still largely unclear. This work aimed to assess transforming growth factor-β1 (TGF-β1), and patatin-like phospholipase domain containing-protein 3 (PNPLA3) genetic variants as risk factors for hepatic fibrosis and hepatocellular carcinoma (HCC) in Egyptian patients with HCV-related liver cirrhosis., Methods: Seventy HCV-related liver cirrhosis patients (Total cirrhosis) who were divided into two groups; 34 patients with HCC (HCC group), and 36 patients without HCC (LC group) and 20 healthy volunteers (control group) were included. Routine laboratory investigations and imaging studies were determined. TGF-β1 (Arg25Pro; 915G>C) and PNPLA3 (I148M; C>G) variants were evaluated using real-time polymerase chain reaction (real-time PCR)., Results: HCC group showed a significantly higher GG genotype distribution of TGF-β1 (Arg25Pro) than the LC group (P= 0.008, OR: 7.083, CI 95%: 1.422 - 35.282). The distributions of GG genotype (P= 0.047) and G allele (P= 0.002, OR: 4.395, CI 95%: 1.622 - 11.911) of PNPLA3 (I148M) were significantly higher in total cirrhosis patients than controls., Conclusion: TGF-β1 (Arg25Pro) GG variant may be associated with HCC risk in HCV-related liver cirrhosis patients, while PNPLA3 (I148M) GG variant may be associated with cirrhosis development but not HCC risk in HCV-related liver cirrhosis patients.

Objective: Hepatocellular carcinoma (HCC) is considered the highest recorded malignancy in Egypt. The shortage of appropriate biomarkers for early detection often results in the late diagnosis of the HCC. Circular RNAs (CircRNAs) are presented as long stranded non-coding RNA that combine covalently to make a sealed circular form which make them very stable. CircRNAs are known to have interpretative role in cancer development and metastasis., Aim: To examine the dysregulation of two new CircRNAs obtained from Circbase database (hsa&#95;circ&#95;0064286 and hsa&#95;circ&#95;0000475) in the serum of HCC patients as predictable diagnostic biomarkers of HCC and their correlation with some liver biochemical parameters., Methods: Sixty clinically diagnosed HCC Egyptian patients and 25 healthy volunteers were enrolled in the study. Expression levels of the selected CircRNAs was evaluated in subjects' serum. Moreover, correlation with liver biochemical parameters, sensitivity, and specificity of studied CircRNAs were estimated., Results: Both circular RNAs were significantly down regulated in HCC patients, which was negatively correlated with ALP, ALT, AST, AFP, and bilirubin levels. Circ&#95;0064286 showed more sensitivity and specificity (88.3% and 96%, respectively)., Conclusion: As far as we know, this is the first study that shed light on the expression levels of both circRNAs in Egyptian HCC patients. They may serve as potential biomarkers for HCC diagnosis. Moreover, those circRNAs draw attention as therapeutic targets for HCC through targeting their sponge miRNAs.

Background: Recent reports suggested relation between Interferon Gamma (IFN-γ) gene polymorphism and the risk of development of HCC on top of hepatic cirrhosis. The aim of this study was to address the predictive value of Interferon Gamma gene receptor (IFN-γR) polymorphisms for the occurrence of hepatocellular carcinoma on top of liver cirrhosis., Patients and Methods: This is a case control study performed on patients selected from the outpatient hepatology clinic, specialized medical hospital, Mansoura University, Egypt, from August 2017 to February 2019. The included patients were categorized into two groups; 60 patients with HCC on top of cirrhosis and 20 patients with hepatic cirrhosis. For all patients IFN-γR polymorphism was identified by RFLP., Results: Our study showed that HCC patients had male predominance. Additionally, diabetes mellitus (DM) was found in 28.3% of total HCC patients. Half of HCC patients in this study were from rural areas (50%). The frequency of AA at position -611 in the IFN-γR (-611 IFN-γR) was significantly higher in the HCC group as compared to cirrhotic group (P=0.021). Moreover; the frequency of CC and CT genotypes of IFN-γR -56 was not significantly different in HCC group as compared to control group (P>0.05). The IFN-γR (-611 IFN-γ) AA genotype significantly increased risk of HCC (OR= 0.78, 95% CI= 0.10-6.39; P= 0.042)., Conclusion: The analysis of IFN-γR -611 single nucleotide gene polymorphism could be a valuable marker for predicting subgroup of cirrhotic patients with high risk of developing HCC.  Cirrhotic patients have AA genotype of IFN-γR-611 recommended to be under close follow up.

Autophagy modulation has recently been addressed as a novel target for overcoming therapeutic resistance in hepatocellular carcinoma (HCC) to currently available anti-HCC therapy. The aim of this study was to investigate the protein and gene expression of Beclin-1 and its correlation with prognosis in HCV-associated HCC in Egyptian patients. This prospective study included 50 patients with HCV-associated-HCC, treated with surgical resection. Immunohistochemistry of antibody and quantitative real-time PCR of Beclin-1 gene were assessed in liver tissues of HCC. A normal-like expression pattern of Beclin-1 was found in 100% of adjacent liver tissues, while in HCC three various patterns were recognized: negative expression [18 (36%)], over expression [16 (32%)] and normal pattern [16 (32%)] (p=0.001). Beclin-1 mRNA in HCC tissues correlated with protein expression with correlation coefficient of 0.774 (p <0.001). Patients with negative expression of Beclin-1 had a significantly poor overall survival rates compared with patients with normal-like expression pattern (p <0.007), which was confirmed by multivariate analysis (p=0.01). Over-expression of Beclin-1 was significantly associated with vascular invasion (p <0.003). However, high tumor histological grade, focal lesion multiplicity, presence of involved margin or cirrhosis were insignificantly related to Becin-1. Beclin-1 altered expression has an important role in development and prognosis of HCC.

Objective: To evaluate the association of gene polymorphisms of the SNP of TNF-α gene -238G>A and IL-18 gene-607C>A with the development of hepatocellular carcinoma among Egyptian patients., Methods: One hundred and fifty patients were allocated to this study; eighty patients with hepatocellular carcinoma (Group A), seventy cancer-free HCV age, and sex-matched patients (Group B). We analyzed two Single nucleotide polymorphisms (SNPs) (TNF-α-238G>A and IL-18-607C>A) by real-time polymerase chain reaction using sequence-specific primers (PCR-SSP)., Results: Significant higher risk of HCC was associated with genotype IL-18-607AA (p <0.001), OR: 5(2.188-11.47), allele IL-18 -607⁄A (P=0.001), OR: 2.1(1.32-3.3). A significant association was found between the size of HFL in the HCC group and different genotypes of IL18 genes (P=0.013) where 62.5% of patients with tumor size >5 cm carried the risky (AA) genotype on the other hand the SNP of TNF-α gene -238G>A showed no statistically significant association between the two groups., Conclusion: The SNP -607C>A in the IL18 gene was associated with increased HCC risk in Egyptian patients suggesting its use as a potential diagnostic non-invasive tool that allows to identify a new group of HCC patients at an earlier stage., .

Background: This study aims to investigate the relation between Survivin gene polymorphisms and the risk of Hepatocellular carcinoma (HCC) resulting from hepatitis C infection among the Egyptian population., Methods: This prospective study was conducted on 164 patients, 57 patients were diagnosed with hepatitis C, where 57 were diagnosed with HCC in addition to 50 healthy volunteers as controls. Genotyping for Survivin rs1042489 and rs8073069 single nucleotide polymorphisms was carried out by the allelic discrimination Real-Time Polymerase Chain Reaction Single Nucleotide Polymorphisms genotyping technology., Results: The results of Survivin rs1042489 polymorphism revealed that the TC and CC genotypes were significantly different between hepatocellular carcinoma patients (OR=15.5, 95%CI: 3.299-72.825,P<0.001), and controls (OR=44, 95%CI: 8.025-241.254, P<0.001). Furthermore, CC genotype was significantly different between cirrhotic and hepatocellular carcinoma patients (OR=19.2, 95%CI: 3.097-119.049, P=0.002). Moreover, the TC genotype shows a significant difference between controls and cirrhotic patients (OR=5.5, 95%CI: 2.111-14.328, P<0.001). However, when comparing TT genotypes, CC+TC genotypes results showed a significant association with increasing the risk of cirrhosis and hepatocellular carcinoma (OR=4.812, 95%CI: 1.893-12.233, P=0.001), (OR=21.607, 95%CI: 4.738-98.532, P<0.01), respectively. On the other hand, there was no significant difference among all studied groups for all genotypes regarding Survivin rs8073069. Also, the CC+GC genotype showed no significant association with increased risk of hepatocellular carcinoma (P=0.999) compared with the GG genotypes., Conclusion: The study indicates that functional Survivin rs1042489 polymorphism may contribute to the risk of hepatocellular carcinoma while Survivin rs8073069 polymorphism has no significant association with increased risk of hepatocellular carcinoma among the studied groups., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The relationship of leptin (LEP) and polymorphism of leptin receptor (LEPR) were studied in patients with hepatocellular carcinoma (HCC) and compared with those with liver cirrhosis to find out the extent of the risk of LEPR on patients with HCC., Methods: Serum LEP level and LEPR Q223R gene polymorphism were determined in 300 patients with liver disease categorized equally into five groups' healthy volunteers, patients with hepatitis C (HCV), patients with non-alcoholic steatohepatitis (NASH),  liver cirrhosis and HCC. LEPR gene was amplified by polymerase chain reaction (PCR) then digested by the MSP1 restriction enzyme., Results: The isolated 212 bp of LEPR was sequenced. The serum LEP level was reduced in patients with cirrhotic and HCC. Serum LEP level had negatively correlated with both tumor grade and size in HCC patients. The data obtained from restriction fragment length polymorphism‑PCR and sequencing revealed the existence of a novel synonymous Q223R single nucleotide polymorphism (SNP) in exon 223 of LEPR gene (1137101). LEPR Gln223Arg, GG and GA genotypes were found in all studied groups. LEPR Gln223Arg, AA genotype was found in NASH, HCC, and control. LEPR Gln223Arg GA genotype is associated with some patients with HCC., Conclusion: GA genotype of LEPR Gln223Arg may be regarded as a probable genetic risk factor for Egyptian patients with HCC.

Liver cirrhosis is an important risk factor for hepatocellular carcinoma. The reported annual incidence of HCC is about 3%-8% in CHC cirrhotic patients. Based on the Cochrane systematic review, there was no clear evidence, on the long-term clinical effects of DAAs in patients achieving SVR, as regard liver cirrhosis-related HCC incidence. The aim of the study was to determine the incidence of HCC in chronic hepatitis C patients genotype IV with liver cirrhosis and advanced liver fibrosis after achieving SVR following DAA treatment in a prospective large cohort of HCV patients with long follow-up. This was a prospective observational cohort study including 2372 CHC patients with advanced liver fibrosis or cirrhosis receiving DAA therapy in outpatient clinics at the Egyptian Liver Research Institute and Hospital since January 2015. Liver fibrosis was assessed using transient elastography. Abdominal ultrasonography and AFP measurement were done at baseline and follow-up visits every 6 months, in addition to triphasic abdominal MSCT when needed. Patients were followed up after achieving SVR12 for at least 12 months. HCC developed in 109 cases during the follow-up period (mean 23.60 ± 8.25 months). Overall HCC incidence was 2.338/100 PY, 95% CI = 1.942-2.814. In patients with cirrhosis, the incidence of HCC was 2.917/100 PY, 95% CI = 2.407-3.535, while in patients with advanced liver fibrosis the incidence of HCC was 0.664/100 PY, 95% CI = 0.333-1.326. In conclusion, the incidence of HCC was reduced in chronic hepatitis C genotype 4 patients with liver cirrhosis (F4) and advanced hepatic fibrosis (F3) who achieved SVR following DAA therapy., (© 2020 John Wiley & Sons Ltd.)

Hepatitis C virus (HCV) is considered leading cause of cirrhosis and hepatocellular carcinoma (HCC). We aimed to examine the association of IL-6 and IL-10 single-nucleotide polymorphisms with the progression of chronic HCV (CHC) infection to cirrhosis and HCC. For comparative purposes, four groups were enrolled; chronic HCV group (CHC, n = 22), HCV-related liver cirrhosis group (HCV-LC, n = 22), HCV-related HCC group (HCV-HCC, n = 54), and an apparently healthy control group (controls, n = 48). HCC diagnosis and staging were in concordance to Barcelona Clinic Liver Cancer (BCLC) staging system. IL-6 rs-1474347 and IL-10 rs-1800896 genotyping was performed by allelic (VIC- and FAM-labeled) discrimination method using assay-on-demand TaqMan real-time PCR assays. For IL-6 rs1474347, the AA genotype was more frequent in CHC, HCV-LC, and HCV-HCC compared to controls. Also, the IL-6 rs1474347 AC genotype was favorable for the progression of HCV chronic infection to cirrhosis and HCC. On the other hand, the IL-10 rs1800896 TT genotype was found to be prominent in the HCC group. Additionally, the IL-10 rs180096 TT genotype was favorable for the progression of chronic HCV infection to cirrhosis and HCC. Furthermore, higher levels of AFP were observed in HCC patients with IL-6 rs1474347 AA genotype and HCC patients with IL-10 rs1800896 CC and TT genotypes. Screening for IL-6 rs 1474347 AC genotype and IL-10 rs180096 TT genotype as well as the determination of AFP level showed to be good markers for examining the susceptibility of HCV Egyptian patients to develop cirrhosis and HCC.

Background and Study Aims: MicroRNAs (miRNAs), small single stranded RNAs, function in the post-transcriptional regulation of gene expression and incorporated in pathogenesis of HCV related chronic liver disease. This study was designed to evaluate the significance of serum miR-21, miR-223, and miR-885-5p as biomarkers in various clinicopathological stages of HCV related chronic liver disease., Patients and Methods: Serum miR-21, miR-223, and miR-885-5p were quantified by quantitative RT PCR in 60 patients with HCV-related liver disease (presumably genotype 4), in addition to 25 healthy controls. HCV patients were classified into: chronic non-cirrhotic HCV (n = 15), HCV related liver cirrhosis (n = 15), and hepatocellular carcinoma (HCC) (n = 30)., Results: Serum levels of miR-885-5p in cirrhotic patients ± HCC (n = 45) were significantly higher than the non-cirrhotic patients (n = 15); p = 0.007 and healthy control; p = 0.001. However, no such significance was detected between HCC and non-HCC HCV patients; p = 0.12. Serum miRNA-885-5p was able to discriminate cirrhosis ± HCC from healthy controls using ROC analysis; AUC 0.85, 87% sensitivity and 80% specificity. On the other hand, HCC patients had significantly higher serum miR-2 1evels than non-HCC patients (non-cirrhotic and cirrhotic groups, n = 30); p = 0.048 and the control group; p = 0.002. ROC could differentiate HCC from control group; AUC 0.89, 80% sensitivity, 80% specificity. Both serum bilirubin and albumin showed significant weak correlation with miRNA-885-5p (r = 0.42, p = 0.001) and (r = -0.27, p = 0.04), respectively but no such correlation was observed with serum miRNA-21. In contrast, miRNA-223 showed no significant difference across the studied groups., Conclusion: Along the spectrum of HCV-related chronic liver disease, miR-885-5p could be a potential marker for advanced liver damage while miR-21 could be a helpful diagnostic marker for HCC., (Copyright © 2019 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.)

Background: Inconsistent results were reported on the association of TLRs polymorphisms with the risk of HCV infection and HCV-related diseases., Objective: to assess the relation between TLR3 rs3775290, TLR7 rs17900 and TLR9 rs352140 SNPs and chronic HCV in the Egyptian cohort and to study their relation to interferon response., Methods: TLR3 rs3775290, TLR7 rs179008 and TLR9 rs352140 gene polymorphisms were typed by RFLP for 100 patients with chronic HCV and 25 with HCC in addition to 100 healthy controls., Results: A significant higher frequency has been found for the CT genotype of TLR3 rs3775290 in chronic HCV infection (p < 0.001) and CC genotype and the combined genotype CC-AT-GA ♀ in controls (p < 0.001). Non-significant associations have been found for studied SNPs and HCC and response to interferon and also the viral load or the degree of fibrosis, however, the higher HCV viral load and the higher grade of fibrosis were associated with treatment failure (p < 0.001)., Conclusion: The heterozygous CT genotype of TLR3 rs3775290 may be a susceptibility risk factor for chronic HCV infection and the homozygous CC and the combined CC-AT-GA ♀ genotypes may be protective. The HCV viral load and the grades of liver fibrosis could be considered a risk factor for interferon treatment failure. It seems that the studied SNPs have no role in HCC development or failure of treatment. However, the small sample size is a limiting factor of the present study when interpreting the negative associations and that the current used cohort does not permit such conclusion., Abbreviations: cHCV=chronic Hepatitis C virus, HCC=hepatocellular carcinoma, TLR=Toll like Receptor, RFLP=Restriction Fragment Length Polymorphism, SNP=Single Nucleotide Polymorphism, IFN-α= interferon alpha.

Background: Chronic infections with HCV (CHC) induce a chronic inflammation which can lead to liver fibrosis and subsequently cirrhosis. A recent study suggests a role of IL-17 polymorphism and serum IL17 in hepatitis B related HCC. These data indicate that the IL-17 G-197A polymorphism may be a good indicator for susceptibility to cancer development., Aim: To investigate the role of the IL17A gene polymorphism, serum IL17 and total IgE in Egyptian population with chronic infections with HCV and HCC., Subjects and Methods: This study was carried out on 40 patients with chronic HCV, 35 patients with hepatocellular carcinoma and 20 healthy persons as control. All subjects were submitted to History taking, clinical examination, abdominal ultrasound, laboratory tests including CBC, liver function tests, alpha fetoprotien, determination of IL17gene polymorphisms by PCR-RFLP, IL17 by ELISA and IgE by immunonephelometric assay., Results: In reference to AA genotype, the frequencies of GG, GA+GG genotypes in the cases with HCC were significantly different from that of the controls (p=0.012, 0.011) and carry 6.12,4.9 respectively fold increase for HCC risk and that of chronic HCV without HCC (p=0.005, 0.004) respectively. However, there was no significant difference in allele frequency in the studied groups (p=0.095). Cases with HCC significantly have higher levels of serum IL17 and IgE than both healthy control and chronic HCV. In conclusion, the present study showed the GG, GG+GA genotypes of IL17A gene is a risk factor for HCC development may be through increased IL17 and IgE and further studies with larger sample size and different populations are recommended., (Copyright © 2015 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)

Hepatocellular carcinoma (HCC) is a hypervascular tumor characterized by neovascularization. The objective of the current study was to determine circulating proangiogenic [vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF), and tumor necrosis factor (TNF-α)] and antiangiogenic [IL-4, IL-12, interferon gamma-induced protein 10 (IP-10), and angiostatin] factors in Egyptian patients with different stages of HCC. Enzyme-linked immunosorbent assay (ELISA) was used to detect the concentrations of these mediators in plasma of 135 HCC patients (57 Child-Pugh A, 24 Child-Pugh B, and 54 Child-Pugh C stage) and 50 healthy subjects. Results showed a significant increase in plasma levels of VEGF (P < 0.001), PDGF (P < 0.001), TNF-α (P < 0.01), angiostatin (P < 0.01), and IP-10 (P < 0.001) and a significant reduction in IL-12 (P < 0.001) in HCC patients in relation to normal controls. Classifying HCC patients based on their Child-Pugh's score revealed that the maximum production of proangiogenic mediators (VEGF and TNF-α) was present in HCC patients with Child-Pugh C score which coincides with maximum reduction in antiangiogenic mediators (IL-4, IL-12, and angiostatin). Taken together, these results indicated that the determination of these factors in different Child-Pugh's scores of HCC might be an important guide in clinical decision making regarding therapy and outcome., (© 2014 Wiley Periodicals, Inc.)

Background and Study Aims: Data about dual hepatitis C (HCV) and B (HBV) co-infection are still scarce, especially in endemic areas such as Egypt. Therefore, we aimed to characterise the virologic and histologic pattern of dual B/C co-infection in a tertiary care centre in Egypt., Patients and Methods: After obtaining approval from the review board, a retrospective design to evaluate the data registry between January 2009 and December 2012 of patients with dual HCV and HBV seropositivity (BC-group) at the Viral Hepatitis Unit in Ministry of Health and Assiut University Hospital, Egypt was conducted. Data for hepatitis B e antigen (HBe-Ag) and anti-HB core status, anti-hepatitis delta virus (anti-HDV), HBV-DNA and HCV-RNA assays and liver biopsy (METAVIR scoring) results were collected. Two other matched groups of mono-HCV (C-group) and HBV (B-group) were selected as controls. All patients were naive for antiviral therapy., Results: A total of 3300 patients were enrolled. Dual infection was observed in 25 (0.7%) patients (all males, mean=35.2±10.2years). Four patients (16%) were HBe-Ag-positive. Six (24%) patients were HBV-DNA-negative and all were positive for HCV RNA. Between groups, raised alanine aminotransferase (ALT) was found in 76%, 41.7% and 49.2% of the BC, B and C groups, respectively (p=0.023). HBV DNA >2000IUml(-1) was more in the B-group than in the BC-group (63.9% vs. 36%; p=0.042) and HCV RNA >800,000IUml(-1) was more in the BC-group than in the C-group (28% vs. 12.3%; p=0.009). Histologically, there is no statistical significant difference between the three groups., Conclusion: Dual hepatitis B/C infection is not uncommon and their virologic and histologic profile is modest. Further evaluation with regard to treatment and long-term follow-up is warranted., (Copyright © 2013 Arab Journal of Gastroenterology. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: Hepatocellular carcinoma (HCC) is one of the most common malignant tumours worldwide. Egypt has the highest prevalence of HCV in the world and the prevalence of HCC is increasing in the last years. The aim was to study epidemiological characteristics of HCC in Egypt., Methods: Retrospective chart review of 1456 Egyptian patients with HCC was done. Records of 1313 patients (1035 males, 278 females; median age 56 years) fulfilling diagnostic criteria for HCC were analysed for clinical, aetiological, radiological and tumour characteristics., Results: The majority of cases (75%) were from rural areas. The most frequent age category affected by HCC was between 51 and 60 years (45.7%); 50% of the patients reported accidental discovery of their hepatic focal lesions. The major presenting symptom was newly developed right hypochondrial pain (66.3%). HCV Ab was detected in 91.32% of the studied patients while HVB infection was reported in 2.51%. 59.3% of patients had AFP levels below 200 ng/ml (the diagnostic level). On studying tumour characteristics, the right lobe of the liver was more frequently occupied by the focal lesions (75.4%) than the left lobe (15.7%) and 12.5% of patients had bilobar affection. Five hundred and six patients (38.6%) had more than one hepatic focal lesion and 228 patients (17.4%) had tumours occupying >50% of the liver., Conclusion: HCC is a major health problem in Egypt and its incidence is increasing. The high prevalence of HCV infection makes screening programmes and surveillance of those patients a very important tool to early detect cases of small HCCs., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Hepatocellular carcinoma (HCC) associated to infection with hepatitis C virus (HCV) has become the fastest-rising cause of cancer-related deaths. Genetic variations may play an important role in the development of HCC in HCV patients. Ghrelin exerts anti-inflammatory, antifibrotic and hepatoprotective effects on chronically injured hepatic tissues. Ghrelin gene shows several single nucleotide polymorphisms (SNPs) including -604G/A, Arg51Gln, and Leu72Met. Hemochromatosis gene (HFE) mutations namely C282Y and H63D may cause hepatic iron overload, thus increasing the risk of HCC in HCV patients., Aim: To investigate the association of progression of HCC with ghrelin and HFE gene polymorphisms in HCV Egyptian patients., Methods: Seventy-nine chronic HCV patients (thirty-nine developed HCC and forty did not), and forty healthy control subjects were included in the study. The polymorphisms were evaluated by PCR/RFLP analysis, and related protein levels were measured by either ELISA or colorimetric assays., Results: The three tested SNPs on ghrelin gene were detected in the studied groups, only one SNP (Arg51Gln) showed significantly higher GA, AA genotypes and A allele frequencies in hepatitis C patients who developed HCC than in hepatitis C patients without HCC and controls. Of the two mutations studied on HFE gene only H63D heterozygous allele was detected, and its frequency did not statistically differ among studied groups., Conclusion: Our results suggest that A allele at position 346 of the ghrelin gene is associated with susceptibility to HCC in hepatitis C patients., (© 2013 Elsevier B.V. All rights reserved.)