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EL-shqnqery HE, Mohamed RH, Samir O, Ayoub I, El-Sayed WM, Sayed AA. miRNome of Child A hepatocellular carcinoma in Egyptian patients. Front Oncol 2023; 13:1137585. [PMID: 37168369 PMCID: PMC10164962 DOI: 10.3389/fonc.2023.1137585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Accepted: 04/03/2023] [Indexed: 05/13/2023] Open
Abstract
INTRODUCTION Hepatocellular carcinoma (HCC) has different etiologies that contribute to its heterogeneity. In regards to the number of HCC patients, Egypt ranks third in Africa and fifteenth worldwide. Despite significant advancements in HCC diagnosis and treatment, the precise biology of the tumor is still not fully understood, which has a negative impact on patient outcomes. METHODS Advances in next-generation sequencing (NGS) have increased our knowledge of the molecular complexity of HCC. RESULTS & DISCUSSION In this research, 16 HCC and 6 tumor adjacent tissues (control) of Child A Egyptian patients were successfully profiled for the expression profile of miRNAs by NGS. Forty-one differentially expressed miRNAs (DEMs) were found by differential expression analysis, with 31 being upregulated and 10 being downregulated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was then conducted on these differentially expressed miRNAs revealing that Sensitivity and specificity analysis showed that hsa-miR-4488, hsa-miR-3178, and hsa-miR-3182 were unique miRNAs as they are expressed in HCC tissues only. These miRNAs were all highly involved in AMPK signaling pathways. However, hsa-miR-214-3p was expressed in control tissues about eight times higher than in cancer tissues and was most abundant in "pathways in cancer and PI3K-Akt signaling pathway" KEGG terms. As promising HCC diagnostic markers, we here suggest hsa-miR-4488, hsa-miR-3178, hsa-miR-3182, and hsa-miR-214-3p. We further urge future research to confirm these markers' diagnostic and prognostic potential as well as their roles in the pathophysiology of HCC.
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Affiliation(s)
- Hend E. EL-shqnqery
- Department of Clinical Pathology, National Liver Institute, Menoufia University, Cairo, Egypt
- Genomics and Epigenomics Program, Department of Basic Research, Children’s Cancer Hospital Egypt, Cairo, Egypt
| | - Rania Hassan Mohamed
- Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt
| | - Omar Samir
- Genomics and Epigenomics Program, Department of Basic Research, Children’s Cancer Hospital Egypt, Cairo, Egypt
| | - Islam Ayoub
- Department of Hepatopancreato Biliary Surgery, National Liver Institute, Menoufia University, Cairo, Egypt
| | - Wael M. El-Sayed
- Department of Zoology, Faculty of Science, Ain Shams University, Cairo, Egypt
| | - Ahmed A. Sayed
- Genomics and Epigenomics Program, Department of Basic Research, Children’s Cancer Hospital Egypt, Cairo, Egypt
- Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt
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Lithy RM, Omar Abdelaziz A, Awad A, Ibrahim Shousha H, Omran D, Mahmoud Nabil M, Hosni Abdelmaksoud A, Mahmoud Elbaz T, Mabrouk M. Meta-learning algorithm development to predict outcomes in patients with hepatitis C virus-related hepatocellular carcinoma. Arab J Gastroenterol 2022; 23:230-234. [PMID: 36400702 DOI: 10.1016/j.ajg.2022.10.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Revised: 06/06/2022] [Accepted: 10/17/2022] [Indexed: 11/17/2022]
Abstract
BACKGROUND AND STUDY AIMS Prediction of prognosis and treatment outcomes for patients with hepatocellular carcinoma (HCC) is complex for most patients. Machine learning predictive analysis can be used to explore the rich information in electronic health records to discover hidden patterns and relationships. We aimed to develop a noninvasive algorithm for predicting outcome treatment options for patients with HCC. PATIENTS AND METHODS This cross-sectional study included 1298 patients with Hepatitis C virus-related HCC attending an HCC multidisciplinary clinic, Kasr Al-Aini Hospital, Cairo University, between 2009 and 2016. Using machine learning analysis, we constructed Reduced Error Pruning (REP) decision tree algorithms and applied Auto-WEKA to select the best classifier out of 39 algorithms. RESULTS The REP-tree algorithm predicted HCC management outcomes with a recall (sensitivity) of 0.658 and a precision (specificity) of 0.653 using only routine data. 854 (65.8%) instances were correctly identified, and 444 (34.2%) instances were incorrectly classified. Out of 31 attributes, liver decompensation was selected by REP-tree as the best predictor of HCC outcome (root node). With Auto-WEKA, the random subspace classifier was chosen as the best predictive algorithm with a recall (sensitivity) of 0.750 and a precision (specificity) of 0.75. There were 974 (75%) correctly classified instances and 324 (25%) incorrectly classified instances, which was better than REP-tree. CONCLUSION Machine learning analysis explores data to discover hidden patterns and trends and enables the development of models to predict HCC treatment outcomes utilizing simple laboratory data. The random subspace classifier predicted the outcome more accurately than REP-tree.
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Affiliation(s)
- Rania M Lithy
- Endemic Medicine and Hepato-gastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ashraf Omar Abdelaziz
- Endemic Medicine and Hepato-gastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Abobakr Awad
- Computer Science Department, Faculty of Computers and Information, Cairo University, Cairo, Egypt
| | - Hend Ibrahim Shousha
- Endemic Medicine and Hepato-gastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Dalia Omran
- Endemic Medicine and Hepato-gastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed Mahmoud Nabil
- Endemic Medicine and Hepato-gastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed Hosni Abdelmaksoud
- Diagnostic and Interventional Radiology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Tamer Mahmoud Elbaz
- Endemic Medicine and Hepato-gastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mahasen Mabrouk
- Endemic Medicine and Hepato-gastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
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Youssef SS, Abbas EAER, Elfiky AM, Seif S, Nabeel MM, Shousha HI, Abdelaziz AO. The impact of polymorphism in PNPLA3 and TM6SF2 genes on the susceptibility and survival of hepatitis C-related hepatocellular carcinoma. EGYPTIAN LIVER JOURNAL 2022; 12:56. [DOI: 10.1186/s43066-022-00212-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Accepted: 08/28/2022] [Indexed: 12/02/2022] Open
Abstract
Abstract
Background
Genetic variants of Patatin-like phospholipase domain-containing protein 3 (PNPLA3) and transmembrane 6 superfamily member 2 (TM6SF2) genes have been reported with the development of hepatocellular carcinoma (HCC). This study aims to explore the role of The PNPLA3 rs738409 and TM6SF2 rs58542926 single-nucleotide polymorphisms (SNPs) on the incidence and survival of HCV-induced HCC in Egyptians.
Methods and results
This case-control study included (120) HCC and (144) hepatitis C virus (HCV) patients. Baseline clinical, laboratory, tumor characteristics data, HCC recurrence, and overall survival were collected. PNPLA3 rs738409 and TM6SF2 rs58542926 polymorphism were detected by TaqMan allelic discrimination assay. We found that HCC patients were significantly older with male predominance. A significant difference between the TT genotypes of TM6SF2 frequency was observed in HCC compared with HCV patients. Moreover, the T allele of TM6SF2 distributions revealed a significant contribution to the different stages of HCC (p=0.03). Both PNPLA3 rs738409 and TM6SF2 rs58542926 variants showed a significant relation with treatment response according to the modified RECIST criteria. Age and diabetes mellitus were the independent factors associated with the development of HCC by multivariate regression analysis.
Conclusions
TM6SF2 rs58542926 polymorphism, not PNPLA3 rs738409, could be implicated in the development of HCV-induced HCC and its progression.
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Mbaga DS, Kenmoe S, Kengne-Ndé C, Ebogo-Belobo JT, Mahamat G, Foe-Essomba JR, Amougou-Atsama M, Tchatchouang S, Nyebe I, Feudjio AF, Kame-Ngasse GI, Magoudjou-Pekam JN, Fokou LKM, Meta-Djomsi D, Maïdadi-Foudi M, Touangnou-Chamda SA, Daha-Tchoffo AG, Selly-Ngaloumo AA, Nayang-Mundo RA, Yéngué JF, Taya-Fokou JB, Kenfack-Momo R, Atembeh Noura E, Demeni Emoh CP, Tazokong HR, Bowo-Ngandji A, Sake CS, Atenguena Okobalemba E, Njiki Bikoi J, Njouom R, Riwom Essama SH. Hepatitis B, C and D virus infections and risk of hepatocellular carcinoma in Africa: A meta-analysis including sensitivity analyses for studies comparable for confounders. PLoS One 2022; 17:e0262903. [PMID: 35061846 PMCID: PMC8782350 DOI: 10.1371/journal.pone.0262903] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2021] [Accepted: 01/09/2022] [Indexed: 01/05/2023] Open
Abstract
INTRODUCTION Africa denotes unique facies for hepatocellular carcinoma (HCC) characterized by a conjunction of low sensitization, restricted access to diagnosis and treatment and associated with the highest incidence and mortality in the world. We investigated whether hepatitis B (HBV), C (HCV) and D (VHD) viruses were etiological agents of HCC in Africa. METHODS Relevant articles were searched in PubMed, Web of Science, African Index Medicus, and African Journal Online databases, as well as manual searches in relevant reviews and included articles. Analytical studies from Africa evaluating the association between HCC development and HBV, HCV, and HDV were included. Relevant studies were selected, data extracted, and the risk of bias assessed independently by at least 2 investigators. The association was estimated using odds ratios (OR) and their 95% confidence interval (95% CI) determined by a random-effects model. Sources of heterogeneity were determined by subgroup analyses. RESULTS A total of 36 case-control studies were included. With controls having non-hepatic disease, the overall results suggested a significantly increased risk of HCC in patients with HBV (HBeAg (OR = 19.9; 95% CI = [3.7-105.2]), HBsAg (OR = 9.9; 95%) CI = [6.2-15.6]) and DNA (OR = 8.9; 95% CI = [5.9-13.4]); HCV (Anti-HCV (OR = 9.4; 95% CI = [6.3-14.0]) and RNA (OR = 16.5; 95% CI = [7.8-34.6]); HDV (Anti-VHD, (OR = 25.8; 95% CI = [5.9-112.2]); and HBV/HCV coinfections (HBV DNA/HCV RNA (OR = 22.5; 95% CI = [1.3-387.8]). With apparently healthy controls, the overall results suggested a significantly increased risk of HCC in patients with HBV (HBsAg, (OR = 8.9; 95% CI = [6.0-13.0]); HCV (Anti-HCV, (OR = 7.7; 95% CI = [5.6-10.6]); and HBV/HCV coinfections (HBsAg/Anti-HCV (OR = 7.8; 95% CI = [4.4-13.6]) Substantial heterogeneity and the absence of publication bias were recorded for these results. CONCLUSIONS In Africa, HBV/HCV coinfections and HBV, HCV, and HDV infections are associated with an increased risk of developing HCC. The implementation of large-scale longitudinal and prospective studies including healthy participants to search for early biomarkers of the risk of progression to HCC is urgently needed.
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Affiliation(s)
| | - Sebastien Kenmoe
- Virology Department, Centre Pasteur of Cameroon, Yaoundé, Cameroon
| | - Cyprien Kengne-Ndé
- Evaluation and Research Unit, National AIDS Control Committee, Yaoundé, Cameroon
| | - Jean Thierry Ebogo-Belobo
- Medical Research Centre, Institute of Medical Research and Medicinal Plants Studies, Yaoundé, Cameroon
| | - Gadji Mahamat
- Department of Microbiology, The University of Yaounde I, Yaoundé, Cameroon
| | | | - Marie Amougou-Atsama
- Centre de Recherche sur les Maladies Émergentes et Re-Emergentes, Institute of Medical Research and Medicinal Plants Studies, Yaoundé, Cameroon
| | | | - Inès Nyebe
- Department of Microbiology, The University of Yaounde I, Yaoundé, Cameroon
| | | | - Ginette Irma Kame-Ngasse
- Medical Research Centre, Institute of Medical Research and Medicinal Plants Studies, Yaoundé, Cameroon
| | | | | | - Dowbiss Meta-Djomsi
- Centre de Recherche sur les Maladies Émergentes et Re-Emergentes, Institute of Medical Research and Medicinal Plants Studies, Yaoundé, Cameroon
| | - Martin Maïdadi-Foudi
- Centre de Recherche sur les Maladies Émergentes et Re-Emergentes, Institute of Medical Research and Medicinal Plants Studies, Yaoundé, Cameroon
| | | | | | | | | | | | | | - Raoul Kenfack-Momo
- Department of Biochemistry, The University of Yaounde I, Yaoundé, Cameroon
| | - Efietngab Atembeh Noura
- Medical Research Centre, Institute of Medical Research and Medicinal Plants Studies, Yaoundé, Cameroon
| | | | | | - Arnol Bowo-Ngandji
- Department of Microbiology, The University of Yaounde I, Yaoundé, Cameroon
| | | | | | - Jacky Njiki Bikoi
- Department of Microbiology, The University of Yaounde I, Yaoundé, Cameroon
| | - Richard Njouom
- Virology Department, Centre Pasteur of Cameroon, Yaoundé, Cameroon
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Kadiri DD, Peela S, Ganguli D. Effect of cirrhosis and hepatitis on the prognosis of liver cancer. THERANOSTICS AND PRECISION MEDICINE FOR THE MANAGEMENT OF HEPATOCELLULAR CARCINOMA 2022:51-72. [DOI: 10.1016/b978-0-323-98806-3.00002-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Ezzat R, Eltabbakh M, El Kassas M. Unique situation of hepatocellular carcinoma in Egypt: A review of epidemiology and control measures. World J Gastrointest Oncol 2021; 13:1919-1938. [PMID: 35070033 PMCID: PMC8713321 DOI: 10.4251/wjgo.v13.i12.1919] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 04/17/2021] [Accepted: 10/18/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the sixth most common primary malignancy worldwide, and the third most common cause of death among cancers worldwide. HCC occurs in several pre-existing conditions, including hepatitis C, hepatitis B virus, and non-alcoholic cirrhosis. Egypt used to be the country with the heaviest hepatitis C virus (HCV) burden. The relationship between HCV and HCC is an important research area. In Egypt, HCC is a significant public health problem. A possible cause for the increasing rates of detection of HCC in Egypt is the mass screening program that was carried by the government for detecting and treating HCV. A multidisciplinary approach is now widely applied to HCC management in health centers all over Egypt. Different treatment modalities are available in Egypt, with success rates comparable to global rates. The Egyptian health authorities have made the elimination of HCV from Egypt a special priority, and this approach should lead to a decrease in number of HCC cases in the near future. In this article we review the current situation of HCC in Egypt, including epidemiological aspects, relevant risk factors for HCC development, strategies, and efforts established by health authorities for the screening and prevention of both HCV and HCC in Egypt. We highlight the different modalities for HCC treatment.
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Affiliation(s)
- Reem Ezzat
- Internal Medicine Department, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
| | - Mohamed Eltabbakh
- Tropical Medicine Department, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt
| | - Mohamed El Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo 11795, Cairo, Egypt
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Shaaban A, Salamah R, Abo Elseud Y, Mohanty A, Albarrak J. Presentation and Outcomes of Hepatocellular Carcinoma in the Arabian Peninsula: A Review of a Single Institution Experience in the Sorafenib Era. J Gastrointest Cancer 2021; 52:85-89. [PMID: 31808059 DOI: 10.1007/s12029-019-00341-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
PURPOSE There is a growing evidence showing that there are geographic differences in hepatocellular carcinoma (HCC). Little is known about the characteristics of hepatocellular carcinoma in the Arabian Peninsula. The present study examines the presentation and outcomes of HCC in a single institution. METHODS A retrospective chart review of patients presented with advanced-stage HCC to Kuwait Cancer Control Center (KCCC) between 2008 and 2018 was conducted. Data collected included patients demographics, HCC risk factors, performance status, Child-Pugh score, pick up of sorafenib, and survival. RESULTS About 111 cases were analyzed. The mean age of the cohort was 61.8 ± 11.4 years and 94 patients (84.7%) were males. HCV and diabetes were the most common risk factors for HCC and presented in 60 patients (54.1%) and 45 patients (40.5%), respectively. About 78 (70.3%) patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 at presentation. Only 29 (26.1%) patients presented with Child-Pugh class A, while 42 (40.4%) patients received sorafenib. The median overall survival was only 3 months. CONCLUSIONS In our cohort, HCV and diabetes were the main risk factors for HCC. The majority of patients was not amenable to sorafenib treatment and carries a very poor prognosis.
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Affiliation(s)
- A Shaaban
- Kuwait Cancer Control Centre, Shuwaikh, Kuwait. .,Minia University Hospital, Menia Governorate, Egypt.
| | - R Salamah
- Kuwait Cancer Control Centre, Shuwaikh, Kuwait
| | | | - A Mohanty
- Kuwait Cancer Control Centre, Shuwaikh, Kuwait
| | - J Albarrak
- Kuwait Cancer Control Centre, Shuwaikh, Kuwait
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Helal M, Yan C, Gong Z. Stimulation of hepatocarcinogenesis by activated cholangiocytes via Il17a/f1 pathway in kras transgenic zebrafish model. Sci Rep 2021; 11:1372. [PMID: 33446803 PMCID: PMC7809472 DOI: 10.1038/s41598-020-80621-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Accepted: 12/11/2020] [Indexed: 01/29/2023] Open
Abstract
It has been well known that tumor progression is dependent on secreted factors not only from tumor cells but also from other surrounding non-tumor cells. In the current study, we investigated the role of cholangiocytes during hepatocarcinogenesis following induction of oncogenic krasV12 expression in hepatocytes using an inducible transgenic zebrafish model. Upon induction of carcinogenesis in hepatocytes, a progressive cell proliferation in cholangiocytes was observed. The proliferative response in cholangiocytes was induced by enhanced lipogenesis and bile acids secretion from hepatocytes through activation of Sphingosine 1 phosphate receptor 2 (S1pr2), a known cholangiocyte receptor involving in cholangiocyte proliferation. Enhancement and inhibition of S1pr2 could accelerate or inhibit cholangiocyte proliferation and hepatocarcinogenesis respectively. Gene expression analysis of hepatocytes and cholangiocytes showed that cholangiocytes stimulated carcinogenesis in hepatocytes via an inflammatory cytokine, Il17a/f1, which activated its receptor (Il17ra1a) on hepatocytes and enhanced hepatocarcinogenesis via an ERK dependent pathway. Thus, the enhancing effect of cholangiocytes on hepatocarcinogenesis is likely via an inflammatory loop.
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Affiliation(s)
- Mohamed Helal
- grid.4280.e0000 0001 2180 6431Department of Biological Sciences, National University of Singapore, Singapore, Singapore ,grid.419615.e0000 0004 0404 7762Marine Pollution Lab, Marine Environment Division, National Institute of Oceanography and Fisheries, Alexandria, Egypt
| | - Chuan Yan
- grid.4280.e0000 0001 2180 6431Department of Biological Sciences, National University of Singapore, Singapore, Singapore
| | - Zhiyuan Gong
- grid.4280.e0000 0001 2180 6431Department of Biological Sciences, National University of Singapore, Singapore, Singapore
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Rashed WM. Current HCC Clinical and Research in Egypt. LIVER CANCER IN THE MIDDLE EAST 2021:313-321. [DOI: 10.1007/978-3-030-78737-0_19] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Amougou-Atsama M, Jean Adrien Atangana P, Noah Noah D, Fewou Moundipa P, Pineau P, Njouom R. The role of hepatitis C virus genotypes and core mutations in hepatocellular carcinoma in Cameroon. J Viral Hepat 2020; 27:880-885. [PMID: 32301239 DOI: 10.1111/jvh.13303] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Revised: 03/18/2020] [Accepted: 03/23/2020] [Indexed: 12/20/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is known to be an important risk factor for hepatocellular carcinoma (HCC) in Cameroon. However, the effect of HCV-related factors on HCC development still remains unknown in the Central Africa. In this study, we investigated the role of HCV genotypes and core mutations in HCC development in Cameroonian patients. METHODS A case-control study was conducted using patients with HCV-related HCC and matched controls individuals with chronic HCV infection but without HCC. HCV genotypes and mutations were determined using a hemi-nested amplification and sequencing analysis focus on the core and NS5B HCV regions. RESULTS We identify HCV genotype 1, 2 and 4 in both groups. Interestingly, genotype 4 was significantly more prevalent in HCC patients (53.3%). Overall, distribution of genotypes was very different between cases and controls (P = 4.2 E-7). The risk factors analysis showed that infection with HCV-4 is strongly associated with HCC development with odd ratio, 95% confidence interval and p-values of 7.4 (95% CI: 2.08-26.6; P = .001). Furthermore, the risk of developing HCC increased even more significantly in case of infection with HCV subtype 4f with the odd ratio of 20.8 (95% CI, 4.1-66.8; P < .001). Mutations K10R, T72E, K74R and G77A were significantly more frequent in patients with HCC. Remarkably, HCV-4f isolates from HCC patients carried significantly more mutations when compared to controls with HCV-4f or others genotypes (P = .0001). CONCLUSIONS Our results indicate that patients infected with HCV-4f or with selected variants affecting HCV core gene are at increased risk to develop HCC.
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Affiliation(s)
| | | | | | - Paul Fewou Moundipa
- Laboratory of Pharmacology and Toxicology of University of Yaoundé I, Yaoundé, Yaoundé, Cameroon
| | - Pascal Pineau
- Unité « Organisation nucléaire et Oncogenèse », INSERM U993, Institut Pasteur, Paris, France
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Abstract
Abstract
Background
This study aimed to report a cancer registry in Clinical Oncology and Nuclear Medicine Department, Mansoura University Hospital in 2015.
Patients and Methods
All cancer patients who were registered in the department of Clinical Oncology and Nuclear Medicine, Mansoura University Hospital in the time period from January 1st, 2015 to December 31st, 2015, were enrolled in this study. The data in the outpatient clinic index including patient’s name, age, sex and diagnosis were collected.
Results
The included patients were 1146 males (43.7%) and 1474 females (56.3%), the male to female ratio was 1:1.3. The median age for patients was 54 years, and it ranged from 1.5 to 93 years. The median age at diagnosis for female and male patients was 52 years and 57 years, respectively. The most common sites for cancer in females were breast (47.2%), thyroid (7.6%), colon and rectum (5.7%), non-Hodgkin (3.6%), uterus, brain and then ovary. However, the most common cancer sites among males were bladder (9.7%), colon and rectum (9.2%), lung (8.5%), hepatobiliary region (7.9%), brain (6.6%), non-Hodgkin lymphoma (6.6%) and then prostatic cancer.
Conclusion
The current report provides a first cancer registry for this hospital based on data, to be further included in cancer statistics.
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Rashed WM, Kandeil MAM, Mahmoud MO, Ezzat S. Hepatocellular Carcinoma (HCC) in Egypt: A comprehensive overview. J Egypt Natl Canc Inst 2020; 32:5. [PMID: 32372179 DOI: 10.1186/s43046-020-0016-x] [Citation(s) in RCA: 108] [Impact Index Per Article: 21.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Accepted: 01/02/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Worldwide, hepatocellular carcinoma (HCC) is a universal problem and its epidemiological data showed variation from place to place. Hepatocellular carcinoma (HCC) is the sixth and fourth common cancer in worldwide and Egypt, respectively. Egypt ranks the third and 15th most populous country in Africa and worldwide, respectively. The aim of this review is to compare the status of HCC in Egypt to that in the worldwide from different issues; risk factors, screening and surveillance, diagnosis and treatment, prevention, as well as research strategy. MAIN BODY The risk factors for HCC in Egypt are of great importance to be reported. The risk factor for HCC are either environmental- or host/genetic-related risk factors. In the last years, there is a tangible improvement of both screening and surveillance strategies of HCC in Egypt. The unprecedented national screening campaign launched by the end of 2018 is a mirror image of this improvement. While the improvement of the HCC prevention requires the governmental health administration to implement health policies. Although the diagnosis of Egyptian HCC patients follows the international guidelines but HCC treatment options are limited in terms of cost. In addition, there are limited Egyptian reports about HCC survival and relapse. Both basic and clinical HCC research in Egypt are still limited compared to worldwide. SHORT CONCLUSION Deep analysis and understanding of factors affecting HCC burden variation worldwide help in customization of efforts exerted to face HCC in different countries especially large country like Egypt. Overall, the presence of a research strategy to fight HCC in Egyptian patients will help in the optimum allocation of available resources to reduce the numbers of HCC cases and deaths and to improve the quality of life.
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Affiliation(s)
- Wafaa M Rashed
- Department of Research, Children's Cancer Hospital-57357, Cairo, Egypt.
| | | | - Mohamed O Mahmoud
- Department of Biochemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt
| | - Sameera Ezzat
- Department of Epidemiology and Prevention Medicine, National Liver Institute, Menoufia University, Menoufia, Egypt
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Yehia SA, Morad WS, Hendy OM, Dorgham LS. Effect of health education intervention on hepatocellular carcinoma risk factor prevention in Menoufia governorate, Egypt. EGYPTIAN LIVER JOURNAL 2020. [DOI: 10.1186/s43066-019-0011-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Hepatocellular carcinoma is an important public health problem worldwide and in Egypt. It has a bad prognosis and few treatment options. HCV and HBV infection and exposure to pesticides and aflatoxins are major risk factors for its development, so paying more attention to prevention via raising population awareness about its risk factors may be useful in lowering HCC incidence. This study was implemented to study knowledge, attitude, and practice (KAP) of a rural community of Menoufia governorate, Egypt, pre- and post-health education intervention about HCC and prevention of its risk factors.
Results
Seroprevalence of HCV among study participants was 12.3%, and the health education intervention about HCC and the prevention of its risk factors was effective in increasing the percent of pre-intervention good knowledge score groups about HCC, HBV, and HCV, pesticides, aflatoxins, and total knowledge score from 66.5%, 88.8%, 83.8, 41.9%, and 73.7% respectively to 98.9%, 100%, 100%, and 98.9% post-intervention (p value = 0.000 for each) and was also effective in increasing the pre-intervention positive attitude score groups from 61.5 to 98.9% post-intervention. It was also effective in increasing the pre-intervention safe practice score groups of male and female study participants from 20% and 23% respectively to 94.3% and 93.1% post-intervention.
Conclusions
Health education intervention was effective in improving KAP about HCC and prevention of its risk factors and could be adopted by MOHP as a part of comprehensive program for HCC prevention in rural communities of Menoufia governorate.
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Tian M, Zhao B, Martin FL, Morais CLM, Liu L, Huang Q, Zhang J, Shen H. Gene-environment interactions between GSTs polymorphisms and targeted epigenetic alterations in hepatocellular carcinoma following organochlorine pesticides (OCPs) exposure. ENVIRONMENT INTERNATIONAL 2020; 134:105313. [PMID: 31731000 DOI: 10.1016/j.envint.2019.105313] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/24/2019] [Revised: 10/17/2019] [Accepted: 11/04/2019] [Indexed: 06/10/2023]
Abstract
Exposure to environmental pollutant organochlorine pesticides (OCPs) and the role of tumour suppressor GSTs gene polymorphisms as well as epigenetic alterations have all been well reported in hepatocarcinogenesis. However, the interplay between environmental risk factors and polymorphic tumour suppressor genes or epigenetic factors in hepatocellular carcinoma (HCC) development remains ambiguous. Herein, we investigated the relationship of three GSTs polymorphisms (GSTT1 deletion, GSTM1 deletion, GSTP1 rs1695) as well as GSTP1 promoter region DNA methylation and HCC risk with a particular focus on the interaction with OCPs exposure among 90 HCC cases and 99 controls in a Chinese population. Serum samples were analysed for OCPs exposure employing gas chromatography coupled with mass selective detector (GC-MS). GSTs polymorphisms and epigenetic alterations were determined using high-resolution melting PCR (HRM PCR) and DNA sequencing. After adjusting for confounders (HBV infection, smoking, alcohol consumption, BMI, age, gender), OCPs exposure and GSTP1 methylation is significantly associated with elevated risk of HCC, while no significance is observed for GSTs polymorphisms. Moreover, the effects of OCPs exposure on HCC risk are more pronounced amongst GSTP1 (Ile/Val + Val/Val) and GSTP1 promoter methylation subjects than those who were GSTP1 (Ile/Ile) and unmethylated subjects. The interactions between OCPs exposure and GSTP1 genotype as well as GSTP1 epigenetic status are statistically significant. The current study demonstrates the importance of gene-environment interactions in the multifactorial development of HCC.
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Affiliation(s)
- Meiping Tian
- Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China.
| | - Benhua Zhao
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China
| | - Francis L Martin
- Lancashire Teaching Hospitals NHS Trust, Royal Preston Hospital, Fulwood, Preston PR2 2HE, UK; School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, UK
| | - Camilo L M Morais
- Lancashire Teaching Hospitals NHS Trust, Royal Preston Hospital, Fulwood, Preston PR2 2HE, UK; School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, UK
| | - Liangpo Liu
- School of Public Health, Shanxi Medical University, Taiyuan 030001, China
| | - Qingyu Huang
- Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China
| | - Jie Zhang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China
| | - Heqing Shen
- Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China.
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Medina-Buelvas DM, Estrada-Muñiz E, Rodríguez-Sosa M, Shibayama M, Vega L. Increased heart fibrosis and acute infection in a murine Chagas disease model associated with organophosphorus pesticide metabolite exposure. Sci Rep 2019; 9:17539. [PMID: 31772338 PMCID: PMC6879754 DOI: 10.1038/s41598-019-54218-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2019] [Accepted: 11/10/2019] [Indexed: 12/16/2022] Open
Abstract
Some reports suggest that exposure to organophosphorus (OP) pesticides increases the incidence of infections. Ethylated dialkylphosphates (EtDAPs) are metabolites of OP pesticides widely distributed with immunomodulatory potential. Chagas disease is produced by Trypanosoma cruzi parasites, and resolution of this infection requires the activation of inflammatory macrophages (MΦ), which results in cardiac fibrosis. Some reports indicate that EtDAPs increase the amount of the anti-inflammatory alternatively activated MΦ (M2; CD206+F4/80+). Therefore, we analyzed the course of T. cruzi infection, MΦ profiles from peritoneal exudate cells (PECs), inflammatory cell infiltration and fibrosis in the heart of BALB/c mice exposed to diethyldithiophosphate (DEDTP), diethylthiophosphate (DETP) or diethylphosphate (DEP, 0.01 g/kg), common DAPs produced by OP pesticides, 24 h before infection with T. cruzi. We found that DEDTP increased the parasite burden in blood by 99% at the peak of the infection and enhanced the myocardial damage due to an increase in infiltrated inflammatory cells (induced by DEDTP or DETP) and fibrosis (induced by EtDAPs). In the PECs, exposure to EtDAPs increased the proportion of the MΦ subpopulations of M2a, M2b and M2d, which are associated with tissue repair. These results indicate that exposure to EtDAPs can exacerbate the acute phase of a parasitic infection and increase the long-term damage to the heart.
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Affiliation(s)
- Dunia Margarita Medina-Buelvas
- Department of Toxicology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Av. Instituto Politécnico Nacional 2508, San Pedro Zacatenco, CP 07360, Gustavo A. Madero, Ciudad de México, México
| | - Elizabet Estrada-Muñiz
- Department of Toxicology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Av. Instituto Politécnico Nacional 2508, San Pedro Zacatenco, CP 07360, Gustavo A. Madero, Ciudad de México, México
| | - Miriam Rodríguez-Sosa
- Biomedicine Unit, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México (UNAM), Avenida de los Barrios 1, Los Reyes Iztacala, CP 54090, Tlalnepantla, Estado de México, México
| | - Mineko Shibayama
- Department of Infectomics and Molecular Pathogenesis, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Av. Instituto Politécnico Nacional 2508, San Pedro Zacatenco, CP 07360, Gustavo A. Madero, Ciudad de México, México
| | - Libia Vega
- Department of Toxicology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Av. Instituto Politécnico Nacional 2508, San Pedro Zacatenco, CP 07360, Gustavo A. Madero, Ciudad de México, México.
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16
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El-Kady DS, Ali NA, Sayed AH, Abdelhaliem MM, Elmegeed GA, Ahmed HH. Assessment of the Antitumor Potentiality of Newly Designed Steroid Derivatives: Pre-Clinical Study. Asian Pac J Cancer Prev 2019; 20:3057-3070. [PMID: 31653155 PMCID: PMC6982653 DOI: 10.31557/apjcp.2019.20.10.3057] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Indexed: 12/03/2022] Open
Abstract
Cancer is recognized as one of the most prevalent contributors to mortality in several nations and it remains one of the common health issues globally. In particular, hepatocellular carcinoma (HCC) has become a public health problem along with the increase of hepatitis B (HBV) and hepatitis C (HCV) virus infections. Based on this fact, our study goaled to synthesize newly hybrid drugs containing heterocyclic rings incorporated to steroid moiety and to examine the potential antitumor activity of the newly designed heterosteroid derivatives against HCC induced in animal model. Several heterocyclic steroids were synthesized 2-7 and confirmed via the analytical and spectral data (IR, 1H NMR13C NMR and Mass spectroscopy). Compounds 3, 4, and 5 were chosen to be investigated as anticancer agents in HCC rat model by means of validated biomarkers (alfa –fetoprotein, endoglin, lipocali-2 and heat shock protein-70). Following administration of compounds 3, 4 or 5, availability of the active tumor marker molecules was significantly dropped and a substantial decrease of the angiogenic and inflammatory mediators was also evident. These findings were supported by the histological examination of liver tissue. Taken together, this study indicates the potential anticancer activity of the newly synthesized heterosteroid derivatives against HCC in vivo. The antitumor activity of these compounds was likely attributable to modulating some signal transduction pathways involved in tumorigenesis, angiogenesis and inflammation.
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Affiliation(s)
- Dina S El-Kady
- Department of Hormones, Medical Research Division, National Research Centre, Dokki, Giza, Egypt
| | - Naglaa A Ali
- Department of Hormones, Medical Research Division, National Research Centre, Dokki, Giza, Egypt
| | - Alaa H Sayed
- Department of Hormones, Medical Research Division, National Research Centre, Dokki, Giza, Egypt.,Department of Applied Medical Sciences, Community College in Al-Qurayyat, Al-Jouf University, KSA
| | - Mervat M Abdelhaliem
- Department of Hormones, Medical Research Division, National Research Centre, Dokki, Giza, Egypt
| | - Gamal A Elmegeed
- Department of Hormones, Medical Research Division, National Research Centre, Dokki, Giza, Egypt
| | - Hanaa H Ahmed
- Department of Hormones, Medical Research Division, National Research Centre, Dokki, Giza, Egypt
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Chikhi Y, Cheraitia S, Ould Gougam R, Lounes F, Zemmouchi C, Belal N, Bendaoud M, Ait Younes S, Bensalem A, Berkane S, Asselah H, Pineau P, Lahcene M. Wide Sexual Dimorphism of Hepatocellular Carcinoma Presentation in Algeria. Gastrointest Tumors 2019; 6:122-136. [PMID: 31768356 DOI: 10.1159/000501453] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2019] [Accepted: 06/09/2019] [Indexed: 12/14/2022] Open
Abstract
Hepatocellular carcinoma (HCC) represents a worrying public health problem in North Africa and particularly in Egypt. The situation is unclear in western North Africa where HCC has been rarely submitted to careful scrutiny. We decided to analyze demographic, biochemical, virological, and clinical data of a series of HCC from Algerian patients to establish the landscape of this tumor in the country. In the present work, we described 337 cases of primary liver cancer from Bologhine Hospital in Algiers, the capital of Algeria. The mean age of patients was 63.8 ± 11.4 years with a male:female sex ratio of 1.5. The most prevalent risk factors were hepatitis C, hepatitis B, and metabolic pathologies (type 2 diabetes and obesity). The mean BMI was 25.6 ± 4.7 at tumor diagnosis. A strong duality of risk factors and tumor presentation between male and female patients was apparent. Women tended to be older (mean 65.4 vs. 62.7 years, p = 0.039) and either seropositive for anti-HCV (60.0 vs. 41.6%, p = 0.0018) resulting primarily from tattoos and/or scarification (47.2 vs. 25.7%, p = 1.0 × 10<sup>-4</sup>) or more often affected by metabolic disorders (mean BMI 26.1 ± 0.7 vs. 25.1 ± 0.5, p = 0.0248) commonly associated with personal antecedents of cholecystectomy (21.2 vs. 5.8%, p = 4.4 × 10<sup>-5</sup>). By contrast, men were younger, poorer survivors (mean 9.3 vs. 13.3 months, p = 0.005), more frequently HBsAg carriers (27.8 vs. 10.5%, p = 4.8 × 10<sup>-5</sup>), and more exposed to lifestyle risk factors such as smoking (39.4 vs. 3.0%, p = 3.9 × 10<sup>-16</sup>) or alcohol use (19.1 vs. 0.7%, 1.5 × 10<sup>-8</sup>). Finally, geographic disparities throughout Algeria were reminiscent of the situation of chronic hepatitis C in the country. A significant excess of cases originated from the region of Batna, Eastern Algeria, already known for its high rate of hepatitis C. Our results suggest that due to culture or sex-dependent biological differences, the tumor process affecting the liver is drastically different between sexes in Algeria.
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Affiliation(s)
- Yazid Chikhi
- Department of Internal medicine and Gastroenterology, EPH Bologhine, Algiers, Algeria
| | - Salima Cheraitia
- Department of Internal medicine and Gastroenterology, EPH Bologhine, Algiers, Algeria
| | - Rachid Ould Gougam
- Department of Internal medicine and Gastroenterology, EPH Bologhine, Algiers, Algeria
| | - Fadila Lounes
- Department of Internal medicine and Gastroenterology, EPH Bologhine, Algiers, Algeria
| | - Chahrazed Zemmouchi
- Department of Internal medicine and Gastroenterology, EPH Bologhine, Algiers, Algeria
| | - Nassila Belal
- Department of Radiology, Hôpital Central de l'Armée, Ain Naadja, Algiers, Algeria
| | | | | | - Aicha Bensalem
- Laboratory of Virology, Institut Pasteur d'Algérie, Sidi Ferruch, Algiers, Algeria
| | - Saadi Berkane
- Department of Gastroenterology, CHU Mustapha, Algiers, Algeria
| | - Hocine Asselah
- Department of Internal medicine and Gastroenterology, EPH Bologhine, Algiers, Algeria
| | - Pascal Pineau
- Unité "Organisation nucléaire et oncogenèse", INSERM U993, Institut Pasteur, Paris, France
| | - Mustapha Lahcene
- Department of Internal medicine and Gastroenterology, EPH Bologhine, Algiers, Algeria
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18
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Abdelmoez FAB, Imam HM, Idriss NK, Wahid LA, Abbas WA, Abozaid MAA, Abdelwahab HM. The Role of Hepatitis C virus and Possible Risk factors in development of Hepatocellular carcinoma: 400 Patients based study. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2019. [DOI: 10.4103/ejim.ejim_50_18] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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19
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Saleh LM, Canioni D, Shamaa S, El-Zaafarany M, Emarah Z, Abdel-Aziz S, Eladle E, Abdelaziz A, Hermine O, Besson C, Abdel-Ghaffar H. High Prevalence of Hepatitis C Virus among B-Cell Non Hodgkin Lymphoma Patients in Mansoura Region (Egypt), ANRS 12263 Study. Mediterr J Hematol Infect Dis 2019; 11:e2019011. [PMID: 30671217 PMCID: PMC6328034 DOI: 10.4084/mjhid.2019.011] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2018] [Accepted: 11/25/2018] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND The prevalence of Hepatitis C virus in Egypt reaches 15%, which is considered the highest in the world. Genotype 4 represents 93 % of Egyptian HCV infections. Non-Hodgkin lymphoma (NHL) is the 5th most common cancer in Egypt. The association between HCV infection and occurrence of B-cell NHL is well known while data are scarce in Eastern countries. OBJECTIVES We aimed to evaluate the prevalence of HCV infection among patients with B-cell NHL and the clinical characteristics of HCV associated B-cell NHL in the Delta region (Mansoura-Egypt). METHODS Between March 2012 and March 2013, 110 adult patients newly diagnosed with B-cell NHL were enrolled in the current study. This study was carried out at Oncology Center, Mansoura University. Study subjects provided serum for HCV testing. RESULTS The prevalence of HCV infection among these patients was 61% (67/110 patients). Among them, 80% (32/40 tested patients) presented with viremia. In contrast with the histological distribution previously described in Northern regions, the majority of HCV associated lymphomas were DLBCLs (72%) followed by SLL/CLL (13%), follicular lymphomas (7.5%) and marginal zone lymphomas (7.5%). CONCLUSIONS B-cell lymphomas are highly associated with HCV infection in Egypt. Further developments are needed to give access to antiviral treatment for these patients.
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Affiliation(s)
- Layla M. Saleh
- Hematology Laboratory, Oncology Center, Mansoura University, Egypt
- Hematology section, Clinical Pathology Department, Faculty of Medicine, Mansoura University, Egypt
| | - Danielle Canioni
- Department of Pathology, Hôpital Necker Enfants Malades, Paris 5 Descartes University, Paris, France
| | - Sameh Shamaa
- Medical Oncology Department, Oncology Center, Mansoura University, Egypt
- Internal Medicine Department, Faculty of Medicine, Mansoura University, Egypt
| | - Maha El-Zaafarany
- Medical Oncology Department, Oncology Center, Mansoura University, Egypt
- Internal Medicine Department, Faculty of Medicine, Mansoura University, Egypt
| | - Ziad Emarah
- Medical Oncology Department, Oncology Center, Mansoura University, Egypt
- Internal Medicine Department, Faculty of Medicine, Mansoura University, Egypt
| | - Sherin Abdel-Aziz
- Hematology Laboratory, Oncology Center, Mansoura University, Egypt
- Hematology section, Clinical Pathology Department, Faculty of Medicine, Mansoura University, Egypt
| | - Entsar Eladle
- Pathology Department, Faculty of Medicine, Mansoura University, Egypt
| | - Alsaeed Abdelaziz
- Internal fellowship, Mansoura University Hospital, Mansoura University, Egypt
| | - Olivier Hermine
- Department of Adult Hematology, Paris 5 Descartes University, Paris, France
- Imagine Institute, Université Sorbonne Paris Cité, Paris, France
| | - Caroline Besson
- Service d’Hématologie-Oncologie, Centre Hospitalier de Versailles, Le Chesnay, France; Université Versailles Saint Quentin en Yvelines, Université Paris-Saclay.; INSERM U 1018, Villejuif, France
| | - Hasan Abdel-Ghaffar
- Hematology Laboratory, Oncology Center, Mansoura University, Egypt
- Hematology section, Clinical Pathology Department, Faculty of Medicine, Mansoura University, Egypt
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20
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Saad-Hussein A, Beshir S, Taha MM, Shahy EM, Shaheen W, Abdel-Shafy EA, Thabet E. Early prediction of liver carcinogenicity due to occupational exposure to pesticides. MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS 2018; 838:46-53. [PMID: 30678827 DOI: 10.1016/j.mrgentox.2018.12.004] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Revised: 12/09/2018] [Accepted: 12/11/2018] [Indexed: 12/12/2022]
Abstract
Several studies linked between pesticides exposure and development of liver cancer, through several mechanisms inform of genotoxicity, cytotoxicity, tumor promotion, immunotoxicity and hormonal actions. This study aimed to estimate novel biomarkers for early prediction of liver malignancy due to occupational exposure to pesticides in two groups of workers with different socioeconomic standard (highly educated urban researchers and low educated rural pesticides sprayers). This study included 50 urban researchers and 50 rural pesticides sprayers occupationally exposed to pesticides. They were compared with 50 non-exposed urban researchers and 50 non-exposed rural subjects. Several tumor biomarkers were estimated; P53 protein, Alfa fetoprotein (AFP), and Alpha-L-fucosidase (AFU). Additionally, telomerase enzyme activity, Relative telomere length (RTL), and DNA damage using comet assay were measured. Furthermore, the glutathione-S-Transferase (GST) gene polymorphisms were identified for both exposed groups. Statistical analysis revealed elevated level of tumor biomarkers among exposed subjects relative to control groups in spite of being within the normal range. Increase in the DNA damage was detected, with shortening of telomere length and decrease in telomerase enzyme activity in pesticides-exposed subjects compared to their controls. Most of these changes were related to the levels of butyrylcholinesterase. Subjects with GSTT1 genotype were suggested to be more susceptible to hepatic carcinogenicity. Telomere relative length and comets assay together with GST genes polymorphisms could be used as early predictors for liver cancer susceptibility among pesticides exposed workers.
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Affiliation(s)
| | - Safia Beshir
- Departments of Environmental and Occupational Medicine, Egypt
| | - Mona M Taha
- Departments of Environmental and Occupational Medicine, Egypt
| | - Eman M Shahy
- Departments of Environmental and Occupational Medicine, Egypt
| | - Weam Shaheen
- Departments of Environmental and Occupational Medicine, Egypt.
| | | | - Eman Thabet
- Clinical Pathology, National Research Centre, Egypt
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21
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Omar H, Taha S, Hassan W, Omar H. Occult hepatitis B infection: a hidden factor of poor response to intervention treatment of hepatocellular carcinoma in chronic hepatitis C patients. COMPARATIVE CLINICAL PATHOLOGY 2018; 27:1273-1279. [DOI: 10.1007/s00580-018-2735-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/14/2017] [Accepted: 04/25/2018] [Indexed: 01/04/2025]
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22
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El-Shazly SF, Eid MA, El-Sourogy HA, Attia GF, Ezzat SA. Evaluation of Serum Dna Integrity as a Screening and Prognostic Tool in Patients with Hepatitis C Virus-Related Hepatocellular Carcinoma. Int J Biol Markers 2018; 25:79-86. [DOI: 10.1177/172460081002500204] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Background Hepatocellular carcinoma (HCC) is a common malignancy in Egypt due to the high frequency of hepatitis C virus (HCV) infection among the general population. Circulating free DNA is a potential molecular marker for the diagnosis and prognosis of malignant tumors. DNA released from apoptotic cells usually consists of short uniform fragments while DNA released from cancer cells is longer. The ratio of long DNA fragments to total DNA (DNA integrity) may be a potential marker for early detection of HCC and its progression in HCV patients. Methods Sera from 25 patients with HCV-related HCC, 25 patients with chronic HCV infection, and 15 healthy volunteers were examined for Alu repeats by quantitative real-time PCR (qPCR) using 2 sets of primers of 115 and 247 base pairs. DNA integrity was calculated as the ratio of 247-bp to 115-bp Alu fragments. Results Compared with healthy volunteers and HCV patients, significantly higher DNA integrity was found in HCC patients. DNA integrity was associated with tumor size, TNM stage, vascular invasion, lymph node involvement, and distant metastasis. DNA integrity had a higher sensitivity and specificity in discriminating HCC from HCV patients than total DNA. Patients with high DNA integrity had a significantly shorter overall survival and high DNA integrity was shown to be an independent prognostic factor for survival in HCV-related HCC. Conclusions DNA integrity is a promising molecular biomarker for detecting HCC in patients with chronic HCV infection; it reflects the progression and metastatic potential of the tumor, and high DNA integrity is associated with short overall survival in HCV-related HCC.
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Affiliation(s)
- Sherien F. El-Shazly
- Department of Clinical Pathology,
Faculty of Medicine, Tanta University, Tanta - Egypt
| | - Manal A. Eid
- Department of Clinical Pathology,
Faculty of Medicine, Tanta University, Tanta - Egypt
| | - Hesham A. El-Sourogy
- Department of Clinical Pathology,
Faculty of Medicine, Tanta University, Tanta - Egypt
| | - Gehan F. Attia
- Department of Clinical Pathology,
Faculty of Medicine, Tanta University, Tanta - Egypt
| | - Sherif A. Ezzat
- Department of Internal Medicine,
Faculty of Medicine, Tanta University, Tanta - Egypt
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23
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Omidvar BA, Tayyari SF, Vakili M, Nekoei AR. Vibrational spectra, normal coordinate analysis, and hydrogen bond investigation of pyridinium perchlorate. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2018; 191:558-565. [PMID: 29102890 DOI: 10.1016/j.saa.2017.10.067] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/01/2017] [Revised: 10/23/2017] [Accepted: 10/25/2017] [Indexed: 06/07/2023]
Abstract
The IR and Raman spectra of pyridine perchlorate salt (PyHClO4) have been recorded in the 4000-300 and 3200-200cm-1 regions, respectively. The structure and vibrational spectra of pyridine salt have been investigated by means of ab initio and density functional theory (DFT) calculations. To examine the efficiency of basis sets in predicting the vibrational spectra of ClO4-1 ion, several basis sets were used with the B3LYP and B2PLYP levels of theory. It was shown that the 6-311(3df) basis set gives reasonably vibrational wavenumbers for simulation of perchlorate ion experimental vibrational wavenumbers. Therefore, the B3LYP/6-311G(3df) level was used to calculate the vibrational spectra of pyridine perchlorate salt in CH3CN solution. For comparison, the vibrational wavenumbers were also calculated at the B3LYP/aug-cc-pVTZ level. The geometry of PyHClO4 was calculated in the gas phase as well as in solutions, using SCRF-PCM method. According to these calculations, the structure and hydrogen bonding in PyHClO4 is highly affected by media. Two hydrogen bonding systems between ClO4-1 and pyridinium ions were recognized. The nature of these hydrogen bonds is theoretically investigated by using atoms in molecule (AIM) method and natural bond orbital (NBO) analysis. A normal coordinate analysis was performed by using the internal coordinates calculated at the B3LYP/6-311G(3df,p) level for the vibrational normal modes of the titled compound.
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Affiliation(s)
- Bibi Amineh Omidvar
- Department of Chemistry, Ferdowsi University of Mashhad, International Campus, Mashhad 91775-1436, Iran
| | | | - Mohammad Vakili
- Department of Chemistry, Ferdowsi University of Mashhad, Mashhad 91775-1436, Iran
| | - Abdo-Reza Nekoei
- Department of Chemistry, Shiraz University of Technology, Shiraz 71555-313, Iran
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24
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Saleh NA, Elshemey WM. Structure-based drug design of novel peptidomimetic cellulose derivatives as HCV-NS3 protease inhibitors. Life Sci 2017; 187:58-63. [PMID: 28842311 DOI: 10.1016/j.lfs.2017.08.021] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2017] [Revised: 08/15/2017] [Accepted: 08/21/2017] [Indexed: 12/28/2022]
Abstract
Hepatitis C Virus (HCV) represents a global health threat not only due to the large number of reported worldwide HCV infections, but also due to the absence of a reliable vaccine for its prevention. HCV NS3 protease is one of the most important targets for drug design aiming at the deactivation of HCV. In the present work, molecular docking simulations are carried out for suggested novel NS3 protease inhibitors applied to the Egyptian genotype 4. These inhibitors are modifications of dimer cellulose by adding a hexa-peptide to the cellulose at one of the positions 2, 3, 6, 2', 3' or 6'. Results show that the inhibitor compound with the hexa-peptide at position 6 shows significantly higher simulation docking score with HCV NS3 protease active site. This is supported by low total energy value of docking system, formation of two H-bonds with HCV NS3 protease active site residues, high binding affinity and increased stability in the interaction system.
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Affiliation(s)
- Noha A Saleh
- Biophysic Department, Faculty of Science, Cairo University, Giza 12613, Egypt
| | - Wael M Elshemey
- Biophysic Department, Faculty of Science, Cairo University, Giza 12613, Egypt,.
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25
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Zayed RA, Omran D, Zayed AA, Elmessery LO. Determinants of Infection Outcome in HCV-Genotype 4. Viral Immunol 2017; 30:560-567. [PMID: 28731371 DOI: 10.1089/vim.2017.0071] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Hepatitis C virus (HCV) infection represents a worldwide health problem and has been for long an attractive point of research due to diversity among different genotypes regarding unique geographical distribution and diverse treatment outcome. HCV is considered a major cause of chronic liver disease and cirrhosis, which leads to liver failure and hepatocellular carcinoma requiring liver transplantation. Of the HCV genotypes identified, HCV genotype 4 (HCV-4) is the least studied. HCV-4 is responsible for ∼10% of HCV infections and is common in the Middle East and Africa; recently it is increasingly prevalent in European Countries. HCV-4 is a continuing epidemic in Egypt, having the highest prevalence of HCV worldwide. "Know your epidemic, know your response" concept necessitates better understanding of HCV-4 characteristics to control disease dissemination and progression, which compromises the life quality of chronic HCV-infected patients. In this review, we discuss the epidemiology, natural history, and treatment options for patients with HCV-4 infection.
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Affiliation(s)
- Rania A Zayed
- 1 Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University , Giza, Cairo, Egypt
| | - Dalia Omran
- 2 Department of Endemic Medicine and Hepato-gastroenterology, Faculty of Medicine, Cairo University , Giza, Cairo, Egypt
| | - Abeer A Zayed
- 3 Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Cairo University , Giza, Cairo, Egypt
| | - Lobna O Elmessery
- 1 Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University , Giza, Cairo, Egypt
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Jackson SS, St. George DM, Loffredo CA, Amr S. Nonoccupational exposure to agricultural work and risk of urinary bladder cancer among Egyptian women. ARCHIVES OF ENVIRONMENTAL & OCCUPATIONAL HEALTH 2017; 72:166-172. [PMID: 27028960 PMCID: PMC5865450 DOI: 10.1080/19338244.2016.1169155] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
Abstract
This study examined the associations between nonoccupational exposure to agricultural work, through husband or head of household (H/HH) occupation, and urinary bladder cancer risk among Egyptian women. A total of 1,167 women (388 bladder cases and 779 age- and residence-matched, population-based controls) from a multicenter case-control study were included in the analysis. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were estimated using logistic regression. Among married women, those who reported H/HH to be an agricultural worker were at increased risk for bladder cancer as compared to those with H/HH in other occupations, AOR = 1.54, 95% CI [1.09, 2.18]; among unmarried women the risk was not increased, AOR = 0.77, 95% CI [0.45, 1.32]. Nonoccupational exposure to agricultural work, defined as living with an agricultural worker, increased the risk for bladder cancer among married Egyptian women.
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Affiliation(s)
- Sarah S. Jackson
- Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - Diane Marie St. George
- Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | | | - Sania Amr
- Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland, USA
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Ismail SA, El Saadany S, Ziada DH, Zakaria SS, Mayah WW, Elashry H, Arafa M, Elmashad N. Cytokeratin-18 in Diagnosis of HCC in Patients with Liver Cirrhosis. Asian Pac J Cancer Prev 2017; 18:1105-1111. [PMID: 28547948 PMCID: PMC5494222 DOI: 10.22034/apjcp.2017.18.4.1105] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Background: Hepatocellular carcinoma (HCC) is a common malignancy that occurs secondary to viral hepatitis B and C cirrhosis under the influence of environmental factors. In early stages, clinical diagnosis is often difficult and distinguishing HCC from cirrhosis and other hepatic masses by conventional tests is frequently not feasible. Physicians usually depend on measuring serum alpha-fetoprotein (AFP), but this marker has low sensitivity and specificity. The aim of this research was to determine any role of serum cytokeratin-18(Ck-18) as a marker for diagnosis of HCC in patients with liver cirrhosis. Patients and methods: We used ELISA to measure the serum levels of AFP and CK 18 in 60 Egyptian patients (30 cirrhotic and 30 with HCC) and 30 controls. Results: The Ck-18 level was significantly elevated in the HCC group (1247.8± 105.3U/L) when compared to the liver cirrhosis (834.1± 38.8 U/L) and control groups (265.2±83.1U/L). Ck-18 as a marker showed 95.6% sensitivity, 93.3% specificity and 98.8% accuracy. The mean serum AFP was 4901.4±2185.8ng/ml in the HCC group, 100.7±71.7 ng/ml in the cirrhotic group, and 4.0±1.2ng/ml in controls. AFP showed 55. 7% sensitivity, 97. 7% specificity and 84.4% accuracy. Combined use of both Ck-18 and AFP improved the sensitivity to 98%. Conclusion: Serum cytokeratin-18 level can be used as a diagnostic biomarker for HCC with a higher sensitivity than AFP.
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Affiliation(s)
- Saber A Ismail
- Department of Tropical Medicine and Infectious Diseases, Faculty of Medicine, University of Tanta, Egypt.
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Pesticide exposure and liver cancer: a review. Cancer Causes Control 2017; 28:177-190. [PMID: 28194594 DOI: 10.1007/s10552-017-0854-6] [Citation(s) in RCA: 60] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2016] [Accepted: 01/18/2017] [Indexed: 02/07/2023]
Abstract
PURPOSE To review the epidemiologic literature examining pesticide exposure and liver cancer incidence. METHODS A search of the MEDLINE and Embase databases was conducted in October 2015. Eligibility criteria included examining hepatocellular carcinoma (HCC) or primary liver cancer, pesticides as an exposure of interest, and individual-level incidence. The review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS Forty-eight papers were assessed for eligibility and 15 studies were included in the review. The majority of studies were conducted in China and Egypt (n = 8), used a case-control design (n = 14), and examined HCC (n = 14). Most studies showed no association between self-reported and/or occupational exposure to pesticides and liver cancer risk. Six studies demonstrated statistically significant positive associations, including three biomarker-based studies (two using pre-diagnostic sera) that reported higher serum levels of dichlorodiphenyltrichloroethane (DDT) were associated with increased HCC risk. Studies indirectly measuring pesticide exposure using self-reported exposure, occupation, job-exposure matrices, or geographic residence demonstrated inconsistent results. These studies were limited by exposure assessment methods, lack of confounder information, minimal case confirmation, selection bias, and/or over-adjustment. CONCLUSIONS There is mixed evidence suggesting a possible association between specific pesticides and HCC risk, with the strongest evidence observed in biomarker-based studies. In particular, organochlorine pesticides, including DDT, may increase HCC risk. Future research should focus on improved pesticide exposure assessment methods, potentially incorporating multiple approaches including biomonitoring while considering the chemicals of interest, historical exposure to address latency periods, and examining specific chemicals and exposure pathways.
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Mobarak L, Omran D, Nabeel MM, Zakaria Z. Fibro markers for prediction of hepatocellular carcinoma in Egyptian patients with chronic liver disease. J Med Virol 2016; 89:1062-1068. [DOI: 10.1002/jmv.24720] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/05/2016] [Indexed: 12/13/2022]
Affiliation(s)
- Lamiaa Mobarak
- National Hepatology and Tropical Medicine Research Institute; Cairo Egypt
| | - Dalia Omran
- Faculty of Medicine; Department of Endemic Medicine and Hepato-gastroenterology; Cairo University; Cairo Egypt
| | - Mohammed M. Nabeel
- Faculty of Medicine; Department of Endemic Medicine and Hepato-gastroenterology; Cairo University; Cairo Egypt
| | - Zeinab Zakaria
- Faculty of Medicine; Department of Endemic Medicine and Hepato-gastroenterology; Cairo University; Cairo Egypt
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Alavian SM, Haghbin H. Relative Importance of Hepatitis B and C Viruses in Hepatocellular Carcinoma in EMRO Countries and the Middle East: A Systematic Review. HEPATITIS MONTHLY 2016; 16:e35106. [PMID: 27226803 PMCID: PMC4875504 DOI: 10.5812/hepatmon.35106] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/28/2015] [Revised: 01/10/2016] [Accepted: 01/27/2016] [Indexed: 12/11/2022]
Abstract
CONTEXT Hepatocellular carcinoma (HCC) is the second most common cancer-related death worldwide. Although many factors including dietary aflatoxin B1 (AFB1) and alcoholic and non-alcoholic fatty liver diseases can lead to HCC, globally most HCC cases are due to hepatitis B virus (HBV) and hepatitis C virus (HCV). Considering the importance of these viral factors in most HCC cases and relative lack of literature from eastern Mediterranean region office of world health organization (EMRO) countries and the Middle East, we decided to perform this systematic review to find distribution of viral etiology of HCC in these regions. EVIDENCE ACQUISITION In this systemic review, we included all studies from 1 January 1989 to 1 September 2015 with at least 20 samples that measured HBV surface antigen (HBsAg) and antibodies to HCV (anti-HCV). The authors searched MEDLINE, Embase, Popline, Web of Science and WHO indexed databases. We searched the following MeSH terms; hepatocellular carcinoma, hepatitis B virus and hepatitis C virus or hepacvirus. Only studies using second- and third-generation HCV assays were included. Only articles studying HCC patients from EMRO countries and the Middle East were analyzed. Duplicate results that reported the same cases more than once were found and omitted. Studies in English and Farsi were reviewed. If the study was eligible, we recorded the following data; the first author, publication year and journal, study population and number and percentage of patients with different serologic statuses. RESULTS We found 44 studies from 12 countries in EMRO and the Middle East. HCC cases from Iran, Lebanon, Turkey and Yemen were mainly due to HBV, while those of North African nations (Egypt, Tunisia, Morocco, Algeria and Somalia) in addition to Saudi Arabia and Pakistan were mostly HCV related. Sudan showed a high seronegativity and HBV infection in its HCC cases. Unfortunately, some countries from EMRO and the Middle East did not have eligible studies. CONCLUSIONS HBV and HCV are important culprits of HCC in EMRO countries and the Middle East and different nations need different strategies to tackle them accordingly. Countries with high rates of HBV such as Turkey should continue their HBV vaccination and also increase sanitation. Nations with high HCV rates such as Egypt should maintain their blood product monitoring in addition to increased sanitation, especially regarding injection drug users (IDU).
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Affiliation(s)
- Seyed Moayed Alavian
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases (BRCGL), Baqiyatallah University of Medical Sciences, Tehran, IR Iran
- Corresponding Author: Seyed Moayed Alavian, Baqiyatallah Research Center for Gastroenterology and Liver Diseases (BRCGL), Tehran Hepatitis Center, Baqiyatallah University of Medical Sciences, P.O.Box: 14155/ 3651, Tehran, IR Iran. Tel/Fax: +98- 2181264070, E-mail:
| | - Hossein Haghbin
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases (BRCGL), Baqiyatallah University of Medical Sciences, Tehran, IR Iran
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Niu J, Lin Y, Guo Z, Niu M, Su C. The Epidemiological Investigation on the Risk Factors of Hepatocellular Carcinoma: A Case-Control Study in Southeast China. Medicine (Baltimore) 2016; 95:e2758. [PMID: 26871825 PMCID: PMC4753921 DOI: 10.1097/md.0000000000002758] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Incidence of hepatocellular carcinoma (HCC) ranked the fifth in male and ninth in the female counterparts, and 50% of incidence HCC cases were occurred in China with high hepatitis B virus (HBV) prevalence. HCC has seriously compromised the health status of general population in China. A case-control study of 314 HCC cases and 346 controls was conducted in Xiamen, which is an epidemic area in China for both hepatitis B infection and HCC. Face-to-face interview was conducted to gather information on demographic characteristics as well as exposure of environmental factors. Commercial enzyme-linked immunosorbent assay kits were used to determine the status of serological markers of HBV infection. Odds ratios and 95% confidence intervals were estimated by using unconditional logistic regression. Multivariate unconditional logistic regression analysis was applied to evaluate the potential interactions of variables or confounders.As expected, HBV and alcohol intake still are the major risk factors of HCC. Liver disease history and passive smoking are also associated with elevated HCC risk. Indoor air pollution and pesticide exposure have newly identified as risk factors of HCC. Fruit and tea intake can significantly lower the HCC risk.The application of HBV vaccine and reduction on alcohol intake should be further promoted in high-risk population. Fruit and tea can be served as chemoprevention in daily life due to their high accessibility.
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Affiliation(s)
- Jianjun Niu
- From the Zhongshan Hospital, Xiamen University (JN); Xiamen Center for Disease Control and Prevention (YL, ZG, MN, CS); and School of Public Health, Xiamen University, Xiamen, Fujian Province, People's Republic of China (CS)
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VoPham T, Brooks MM, Yuan JM, Talbott EO, Ruddell D, Hart JE, Chang CCH, Weissfeld JL. Pesticide exposure and hepatocellular carcinoma risk: A case-control study using a geographic information system (GIS) to link SEER-Medicare and California pesticide data. ENVIRONMENTAL RESEARCH 2015; 143:68-82. [PMID: 26451881 PMCID: PMC4641787 DOI: 10.1016/j.envres.2015.09.027] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/26/2015] [Revised: 09/18/2015] [Accepted: 09/22/2015] [Indexed: 05/04/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, is associated with low survival. U.S. studies examining self-reported pesticide exposure in relation to HCC have demonstrated inconclusive results. We aimed to clarify the association between pesticide exposure and HCC by implementing a novel data linkage between Surveillance, Epidemiology, and End Results (SEER)-Medicare and California Pesticide Use Report (PUR) data using a geographic information system (GIS). METHODS Controls were frequency-matched to HCC cases diagnosed between 2000 and 2009 in California by year, age, race, sex, and duration of residence in California. Potential confounders were extracted from Medicare claims. From 1974 to 2008, pounds (1 pound represents 0.45 kg) of applied organophosphate, organochlorine, and carbamate pesticides provided in PURs were aggregated to the ZIP Code level using area weighting in a GIS. ZIP Code exposure estimates were linked to subjects using Medicare-provided ZIP Codes to calculate pesticide exposure. Agricultural residents were defined as living in ZIP Codes with a majority area intersecting agricultural land cover according to the 1992, 2001, and 2006 National Land Cover Database (NLCD) rasters. Multivariable conditional logistic regression was used to estimate the association between pesticide exposure and HCC. RESULTS Among California residents of agriculturally intensive areas, previous annual ZIP Code-level exposure to over 14.53 kg/km(2) of organochlorine pesticides (75(th) percentile among controls) was associated with an increased risk of HCC after adjusting for liver disease and diabetes (adjusted odds ratio [OR] 1.87, 95% confidence interval [CI] 1.17, 2.99; p=0.0085). ZIP Code-level organochlorines were significantly associated with an increased risk of HCC among males (adjusted OR 2.76, 95% CI 1.58, 4.82; p=0.0004), but not associated with HCC among females (adjusted OR 0.83, 95% CI 0.35, 1.93; p=0.6600) (interaction p=0.0075). CONCLUSIONS This is the first epidemiologic study to use GIS-based exposure estimates to study pesticide exposure and HCC. Our results suggest that organochlorine pesticides are associated with an increase in HCC risk among males but not females.
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Affiliation(s)
- Trang VoPham
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 De Soto Street, Pittsburgh, PA 15261, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, United States; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, United States.
| | - Maria M Brooks
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 De Soto Street, Pittsburgh, PA 15261, United States.
| | - Jian-Min Yuan
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 De Soto Street, Pittsburgh, PA 15261, United States; Division of Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Pittsburgh, PA 15232, United States.
| | - Evelyn O Talbott
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 De Soto Street, Pittsburgh, PA 15261, United States.
| | - Darren Ruddell
- Spatial Sciences Institute, University of Southern California, 3616 Trousdale Parkway AHF B55, Los Angeles, CA 90089, United States.
| | - Jaime E Hart
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, United States; Department of Environmental Health, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, United States.
| | - Chung-Chou H Chang
- Division of General Internal Medicine, University of Pittsburgh School of Medicine, 200 Meyran Avenue Suite 200, Pittsburgh, PA 15213, United States.
| | - Joel L Weissfeld
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 De Soto Street, Pittsburgh, PA 15261, United States; Division of Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Pittsburgh, PA 15232, United States.
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Mohlman MK, Saleh DA, Ezzat S, Abdel-Hamid M, Korba B, Shetty K, Amr S, Loffredo CA. Viral transmission risk factors in an Egyptian population with high hepatitis C prevalence. BMC Public Health 2015; 15:1030. [PMID: 26446713 PMCID: PMC4596377 DOI: 10.1186/s12889-015-2369-y] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2015] [Accepted: 09/29/2015] [Indexed: 12/13/2022] Open
Abstract
Background Egypt has the world’s highest prevalence of infection with hepatitis C virus (HCV), which is a major cause of hepatocellular carcinoma. The high HCV prevalence is largely attributed to the parenteral antischistosomal therapy (PAT) campaigns conducted from the 1950s through the 1980s; however, the primary modes of transmission in the post-PAT period are not well known. In this study we examined the associations between HCV prevalence and exposures to risk factors, including PAT, in a high HCV prevalence population. Methods Using a cross-sectional design, we examined the associations between demographic characteristics and risk factors for HCV transmission and HCV positivity prevalence among a sample of Egyptian residents. Data were collected through an interview-administered survey, and the association estimates were determined using χ2 and logistic regression. Results The highest HCV positivity prevalence was observed in cohorts born before 1960, and declined precipitously thereafter; whereas the proportion of subjects reporting PAT remained relatively stable. Being male, having a rural residence, and having received PAT were all associated with HCV positivity; however, PAT alone could not account for the high prevalence of HCV. Conclusions In Egypt, PAT and other transmission factors yet to be identified, as well as cohorts born before the 1960s and infected with HCV, are most likely the main contributors to the current HCV endemic.
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Affiliation(s)
- Mary Kate Mohlman
- Lombardi Cancer Center, Georgetown University, 3970 Reservoir Rd, Washington, DC, 20057, USA.
| | | | | | | | - Brent Korba
- Lombardi Cancer Center, Georgetown University, 3970 Reservoir Rd, Washington, DC, 20057, USA.
| | - Kirti Shetty
- Lombardi Cancer Center, Georgetown University, 3970 Reservoir Rd, Washington, DC, 20057, USA.
| | - Sania Amr
- University of Maryland School of Medicine, Baltimore, MD, USA.
| | - Christopher A Loffredo
- Lombardi Cancer Center, Georgetown University, 3970 Reservoir Rd, Washington, DC, 20057, USA.
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Omran DAEH, Awad AH, Mabrouk MAER, Soliman AF, Aziz AOA. Application of data mining techniques to explore predictors of HCC in Egyptian patients with HCV-related chronic liver disease. Asian Pac J Cancer Prev 2015; 16:381-5. [PMID: 25640385 DOI: 10.7314/apjcp.2015.16.1.381] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
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 ≥50.3 ng/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 (≥50.3 ng/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%.
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Affiliation(s)
- Dalia Abd El Hamid Omran
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt E-mail : ;
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Chitapanarux T, Phornphutkul K. Risk Factors for the Development of Hepatocellular Carcinoma in Thailand. J Clin Transl Hepatol 2015; 3:182-8. [PMID: 26623264 PMCID: PMC4663199 DOI: 10.14218/jcth.2015.00025] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2015] [Revised: 08/25/2015] [Accepted: 08/28/2015] [Indexed: 01/25/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common type of liver cancer worldwide. The incidence of HCC is on the rise in Thailand, where it has become the most common malignancy in males and the third most common in females. Here, we review some of the risk factors that have contributed to this increase in HCC incidence in the Thai population. Hepatitis B virus (HBV) is the main etiologic risk factor for HCC, followed by hepatitis C virus (HCV). Patients with HBV genotype C have a higher positive rate of hepatitis B early antigen (HBeAg) and progress to cirrhosis and HCC earlier than genotype B. For HCV patients, 16% developed HCC associated cirrhosis by year 5 after diagnosis, and the cumulative risk for death from HCC at year 10 was 60%. Dietary exposure to the fungal hepatocarcinogen aflatoxin B1 has been shown to interact synergistically with HBV infection to increase the risk of early onset HCC. Chronic alcohol abuse remains an important risk factor for malignant transformation of hepatocytes, frequently in association with alcohol-induced cirrhosis. In recent years, obesity and metabolic syndrome have markedly increased the incidence of HCC and are important causes of HCC in some resource-rich regions.
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Affiliation(s)
- Taned Chitapanarux
- Division of Gastrohepatology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
- Correspondence to: Taned Chitapanarux, Division of Gastrohepatology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand. Tel: +66-53-945482, Fax: +66-53-945481, E-mail:
| | - Kannika Phornphutkul
- Division of Gastrohepatology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
- Gastrohepatology unit, Rajavej Chiang Mai Hospital, Chiang Mai, Thailand
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Saleh DA, Amr S, Jillson IA, Wang JHY, Crowell N, Loffredo CA. Preventing hepatocellular carcinoma in Egypt: results of a Pilot Health Education Intervention Study. BMC Res Notes 2015; 8:384. [PMID: 26319021 PMCID: PMC4553015 DOI: 10.1186/s13104-015-1351-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2014] [Accepted: 08/17/2015] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC), one of the most fatal malignancies, is particularly prevalent in Egypt, where we previously found deficiencies in knowledge concerning HCC and its risk factors. Hepatitis B and C viral infections are highly prevalent in Egypt, pesticides are very commonly used, and diets are often contaminated by aflatoxin, especially in rural areas. METHODS We conducted a study to pilot test a health education intervention addressing HCC, its risk factors, and its main modes of prevention. It included four health education modules: HCC, hepatitis viruses, pesticides and aflatoxin. We used a pre- and post-intervention set of questionnaires to assess knowledge gained by the participants. RESULTS A total of 25 participants from a village in the Nile Delta area attended the health education session and completed the questionnaires. The education intervention significantly increased the participants' knowledge on HCC and its risk factors, particularly regarding the use of pesticides at home and aflatoxin contaminated foods (both p < 0.05). Overall, there was a 12% increase in the number of participants who believed that HCC could be prevented, and they reported their intention to practice prevention for HCC risk factors. CONCLUSIONS We found that the education intervention we pilot tested was feasible and proved effective in increasing participants' knowledge. Future efforts should focus on implementing targeted education programs in high-risk populations in Egypt.
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Affiliation(s)
| | - Sania Amr
- University of Maryland, Baltimore, MD, USA.
| | - Irene A Jillson
- Department of Oncology, Georgetown University, 3970 Reservoir Rd, Washington DC, 20057, USA.
| | - Judy Huei-yu Wang
- Department of Oncology, Georgetown University, 3970 Reservoir Rd, Washington DC, 20057, USA.
| | - Nancy Crowell
- Department of Oncology, Georgetown University, 3970 Reservoir Rd, Washington DC, 20057, USA.
| | - Christopher A Loffredo
- Department of Oncology, Georgetown University, 3970 Reservoir Rd, Washington DC, 20057, USA.
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Mohamed RA, Maghraby HM, Abd El Salam EM, Nageb HM, Ahmad EE, Mohamed NA. Evaluation of serum endoglin as noninvasive marker in hepatocellular carcinoma. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2015. [DOI: 10.4103/1110-7782.155832] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
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Amr S, Dawson R, Saleh DA, Magder LS, St George DM, El-Daly M, Squibb K, Mikhail NN, Abdel-Hamid M, Khaled H, Loffredo CA. Pesticides, gene polymorphisms, and bladder cancer among Egyptian agricultural workers. ARCHIVES OF ENVIRONMENTAL & OCCUPATIONAL HEALTH 2015; 70:19-26. [PMID: 24219772 PMCID: PMC4018465 DOI: 10.1080/19338244.2013.853646] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/23/2023]
Abstract
UNLABELLED This study examined the associations between pesticide exposure, genetic polymorphisms for NAD(P)H quinone oxidoreductase I (NQO1) and superoxide dismutase 2 (SOD2), and urinary bladder cancer risk among male agricultural workers in Egypt. Logistic regression was used to analyze data from a multicenter case-control study and estimate adjusted odds ratio (OR) and 95% confidence interval (CI). Exposure to pesticides was associated with increased bladder cancer risk (odds ratio (95% confidence interval): 1.68 (1.23-2.29)) in a dose-dependent manner. The association was slightly stronger for urothelial (1.79 (1.25-2.56)) than for squamous cell (1.55 (1.03-2.31)), and among participants with combined genotypes for low NQO1 and high SOD2 (2.14 (1.19-3.85)) activities as compared with those with high NQO1 and low SOD2 genotypes (1.53 (0.73-3.25)). In conclusion, among male agricultural workers in Egypt, pesticide exposure is associated with bladder cancer risk and possibly modulated by genetic polymorphism.
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Affiliation(s)
- Sania Amr
- a Department of Epidemiology and Public Health , University of Maryland School of Medicine , Baltimore , Maryland , USA
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Amr S, Iarocci EA, Nasr GR, Saleh D, Blancato J, Shetty K, Loffredo CA. Multiple pregnancies, hepatitis C, and risk for hepatocellular carcinoma in Egyptian women. BMC Cancer 2014; 14:893. [PMID: 25432765 PMCID: PMC4258798 DOI: 10.1186/1471-2407-14-893] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2014] [Accepted: 11/20/2014] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The reasons for the worldwide sex disparity in the incidence of hepatocellular carcinoma (HCC) remain elusive. We investigated the role of multiple pregnancies on the associations between viral hepatitis C (HCV) infection and HCC risk among Egyptian women. METHODS We used data collected from blood specimens and questionnaires administered to female HCC cases and controls in Cairo, Egypt, from 1999 through 2009. HCV infection was defined as being sero-positive for either anti-HCV antibodies or HCV-RNA. Using logistic regression models we calculated odds ratios (OR) and 95% confidence intervals (CI) to estimate the associations between being HCV positive and HCC risk, and how it is modified by the number of pregnancies, after adjustment for other factors, including hepatitis B status. RESULTS Among 132 confirmed female cases and 669 controls, the risk of HCV-related HCC increased with the number of pregnancies. Women infected with HCV had higher risk for HCC if they had more than five pregnancies, as compared to those who had five or fewer pregnancies (adjusted OR (95% CI): 2.33 (1.29-4.22)). The association of HCV infection with HCC risk was significantly greater among the former (21.42 (10.43-44.00)) than among the latter (6.57 (3.04-14.25)). CONCLUSION Having multiple pregnancies increases the risk of HCV-related HCC among Egyptian women, raising questions about the roles of estrogens and other pregnancy-related hormones in modulating HCV infection and its progression to HCC.
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Affiliation(s)
- Sania Amr
- />Department of Epidemiology and Public Health, University of Maryland School of Medicine, 660 West Redwood Street, Baltimore, MD 21201 USA
| | - Emily A Iarocci
- />Departments of Oncology, Surgery and Microbiology, Georgetown University, Washington, DC, USA
| | - Ghada R Nasr
- />Department of Community Health, Cairo University, Cairo, Egypt
| | - Doa’a Saleh
- />Department of Community Health, Cairo University, Cairo, Egypt
| | - Jan Blancato
- />Departments of Oncology, Surgery and Microbiology, Georgetown University, Washington, DC, USA
| | - Kirti Shetty
- />Departments of Oncology, Surgery and Microbiology, Georgetown University, Washington, DC, USA
| | - Christopher A Loffredo
- />Departments of Oncology, Surgery and Microbiology, Georgetown University, Washington, DC, USA
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Cancer incidence in egypt: results of the national population-based cancer registry program. J Cancer Epidemiol 2014; 2014:437971. [PMID: 25328522 PMCID: PMC4189936 DOI: 10.1155/2014/437971] [Citation(s) in RCA: 357] [Impact Index Per Article: 32.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2014] [Revised: 09/01/2014] [Accepted: 09/07/2014] [Indexed: 12/15/2022] Open
Abstract
Background. This paper aims to present cancer incidence rates at national and regional level of Egypt, based upon results of National Cancer Registry Program (NCRP). Methods. NCRP stratified Egypt into 3 geographical strata: lower, middle, and upper. One governorate represented each region. Abstractors collected data from medical records of cancer centers, national tertiary care institutions, Health Insurance Organization, Government-Subsidized Treatment Program, and death records. Data entry was online. Incidence rates were calculated at a regional and a national level. Future projection up to 2050 was also calculated. Results. Age-standardized incidence rates per 100,000 were 166.6 (both sexes), 175.9 (males), and 157.0 (females). Commonest sites were liver (23.8%), breast (15.4%), and bladder (6.9%) (both sexes): liver (33.6%) and bladder (10.7%) among men, and breast (32.0%) and liver (13.5%) among women. By 2050, a 3-fold increase in incident cancer relative to 2013 was estimated. Conclusion. These data are the only available cancer rates at national and regional levels of Egypt. The pattern of cancer indicated the increased burden of liver cancer. Breast cancer occupied the second rank. Study of rates of individual sites of cancer might help in giving clues for preventive programs.
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Saleh DA, Amr S, Jillson IA, Wang JHY, Khairy WA, Loffredo CA. Knowledge and perceptions of hepatitis C infection and pesticides use in two rural villages in Egypt. BMC Public Health 2014; 14:501. [PMID: 24886607 PMCID: PMC4050414 DOI: 10.1186/1471-2458-14-501] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2013] [Accepted: 05/06/2014] [Indexed: 12/11/2022] Open
Abstract
Background Hepatocellular carcinoma (HCC), one of the most fatal types of malignancy, is increasing worldwide, and particularly in Egypt where there is a confluence of its contributing factors, including high prevalence of hepatitis C virus (HCV) infection, widespread use of pesticides, and diets that are contaminated by aflatoxin B1 (AFB1) in rural areas. We investigated knowledge, attitudes, and prevention practices related to HCV infection and pesticides use in rural Egypt, where over half of the population resides and agriculture is the predominant occupation. Methods From two rural villages we recruited 67 residents aged 18–80 years, who completed a 40-item survey that included questions about demographics, knowledge of and protective measures relevant to pesticides use in the home and in agriculture, awareness and perceptions of HCV infection and its treatment and prevention. Results Among the 67 study participants, gender distribution was equal, the mean age was 47.2, and one third never attended school. More than 50% reported using pesticides at home, but fewer reported having some knowledge about its health effects. Twelve participants were agricultural workers, and 11 of them applied pesticides in the field and knew about their toxicity; however only one person was correctly using the appropriate protective equipment. Among all the participants, 52 did not know what causes HCV infection, and 42 of those who knew it was a virus mentioned incorrect modes of transmission; and 30 did not know the disease manifestations. Conclusion In rural Egypt, there is a significant lack of knowledge of HCV infection and its transmission mode and limited use of protective measures against pesticides despite familiarity with these chemicals.
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Affiliation(s)
| | | | | | | | | | - Christopher A Loffredo
- Lombardi Cancer Center, Georgetown University, 3970 Reservoir Rd, Washington, DC 20057, USA.
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Abou El Azm AR, Yousef M, Mansour N, Awad A, El Dardiry S, Abdel Aziz I. New Insights on Non-B non-C Hepatocellular Carcinoma in Mid Delta Region, Egypt. J Gastrointest Cancer 2014; 45:276-83. [DOI: 10.1007/s12029-013-9573-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Abdelaziz AO, Elbaz TM, Shousha HI, Ibrahim MM, Rahman El-Shazli MA, Abdelmaksoud AH, Aziz OA, Zaki HA, Elattar IA, Nabeel MM. Survival and prognostic factors for hepatocellular carcinoma: an Egyptian multidisciplinary clinic experience. Asian Pac J Cancer Prev 2014; 15:3915-3920. [PMID: 24935574 DOI: 10.7314/apjcp.2014.15.9.3915] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/19/2025] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a dismal tumor with a high incidence, prevalence and poor prognosis and survival. Management of HCC necessitates multidisciplinary clinics due to the wide heterogeneity in its presentation, different therapeutic options, variable biologic behavior and background presence of chronic liver disease. We studied the different prognostic factors that affected survival of our patients to improve future HCC management and patient survival. MATERIALS AND METHODS This study is performed in a specialized multidisciplinary clinic for HCC in Kasr El Eini Hospital, Cairo University, Egypt. We retrospectively analyzed the different patient and tumor characteristics and the primary mode of management applied to our patients. Further analysis was performed using univariate and multivariate statistics. RESULTS During the period February 2009 till February 2013, 290 HCC patients presented to our multidisciplinary clinic. They were predominantly males and the mean age was 56.5 ± 7.7 years. All cases developed HCC on top of cirrhosis that was mainly due to HCV (71%). Most of our patients were Child-Pugh A (50%) or B (36.9%) and commonly presented with small single lesions. Transarterial chemoembolization was the most common line of treatment used (32.4%). The overall survival was 79.9% at 6 months, 54.5% at 1 year and 22.4% at 2 years. Serum bilirubin, site of the tumor and type of treatment were the significant independent prognostic factors for survival. CONCLUSIONS Our main prognostic variables are the bilirubin level, the bilobar hepatic affection and the application of specific treatment (either curative or palliative). Multidisciplinary clinics enhance better HCC management.
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Affiliation(s)
- Ashraf Omar Abdelaziz
- Department Endemic Hepatogastroenterology, National Cancer Institute, Cairo University, Cairo, Egypt E-mail :
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Zhu WW, Guo JJ, Guo L, Jia HL, Zhu M, Zhang JB, Loffredo CA, Forgues M, Huang H, Xing XJ, Ren N, Dong QZ, Zhou HJ, Ren ZG, Zhao NQ, Wang XW, Tang ZY, Qin LX, Ye QH. Evaluation of midkine as a diagnostic serum biomarker in hepatocellular carcinoma. Clin Cancer Res 2013; 19:3944-3954. [PMID: 23719264 PMCID: PMC6314491 DOI: 10.1158/1078-0432.ccr-12-3363] [Citation(s) in RCA: 96] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
PURPOSE To evaluate the value of serum midkine (MDK) as a diagnostic biomarker in hepatocellular carcinoma, particularly for those with negative alpha-fetoprotein (AFP) and at an early stage. EXPERIMENTAL DESIGN MDK expression in tumors was assessed by immunohistochemistry from 105 patients with hepatocellular carcinomas or liver cirrhosis. Serum MDK levels were detected by ELISA in 933 participants including hepatocellular carcinomas and hospital controls from different medical centers. Sensitivities and specificities of serum MDK in diagnosing hepatocellular carcinoma according to AFP level and Barcelona Clinic Liver Cancer (BCLC) stage were analyzed. RESULTS MDK levels were significantly elevated in hepatocellular carcinoma tissues as well as serum samples. The sensitivity of serum MDK for hepatocellular carcinoma diagnosis was much higher than that of AFP (86.9% vs. 51.9%) with similar specificities (83.9% vs. 86.3%). Notably, serum MDK had an outstanding performance in distinguishing AFP-negative hepatocellular carcinomas from different controls: In those AFP-negative hepatocellular carcinomas, the sensitivity could reach as high as 89.2%. Moreover, receiver operating characteristic (ROC) curve analysis also showed that serum MDK had a better performance compared with AFP in distinguishing early-stage hepatocellular carcinomas as well as small hepatocellular carcinomas. Even in very early-stage hepatocellular carcinomas, MDK showed an obviously higher sensitivity compared with AFP (80% vs. 40%). Furthermore, serum MDK level was significantly decreased in patients with hepatocellular carcinomas after curative resection and re-elevated when tumor relapse occurred. CONCLUSIONS Serum MDK is significantly elevated in most hepatocellular carcinomas, including those with negative AFP and at an early stage, which may serve as a novel diagnostic marker in early diagnosis and postoperative monitoring of hepatocellular carcinomas.
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Affiliation(s)
- Wen-Wei Zhu
- Liver Cancer Institute and Zhongshan Hospital, Institutes of Biomedical Science
- Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education
| | - Jia-Jian Guo
- Liver Cancer Institute and Zhongshan Hospital, Institutes of Biomedical Science
- Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education
| | - Lei Guo
- Liver Cancer Institute and Zhongshan Hospital, Institutes of Biomedical Science
- Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education
| | - Hu-Liang Jia
- Liver Cancer Institute and Zhongshan Hospital, Institutes of Biomedical Science
- Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education
| | - Ming Zhu
- Department of Biostatistics, School of Public Health, Fudan University
| | - Ju-Bo Zhang
- Liver Cancer Institute and Zhongshan Hospital, Institutes of Biomedical Science
- Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education
| | | | - Marshonna Forgues
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland
| | - Hua Huang
- Department of Abdominal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Xu-Jian Xing
- Liver Cancer Institute and Zhongshan Hospital, Institutes of Biomedical Science
- Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education
| | - Ning Ren
- Liver Cancer Institute and Zhongshan Hospital, Institutes of Biomedical Science
- Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education
| | - Qiong-Zhu Dong
- Liver Cancer Institute and Zhongshan Hospital, Institutes of Biomedical Science
- Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education
| | - Hai-Jun Zhou
- Liver Cancer Institute and Zhongshan Hospital, Institutes of Biomedical Science
- Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education
| | - Zheng-Gang Ren
- Liver Cancer Institute and Zhongshan Hospital, Institutes of Biomedical Science
- Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education
| | - Nai-Qing Zhao
- Department of Biostatistics, School of Public Health, Fudan University
| | - Xin Wei Wang
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland
| | - Zhao-You Tang
- Liver Cancer Institute and Zhongshan Hospital, Institutes of Biomedical Science
- Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education
| | - Lun-Xiu Qin
- Liver Cancer Institute and Zhongshan Hospital, Institutes of Biomedical Science
- Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education
| | - Qing-Hai Ye
- Liver Cancer Institute and Zhongshan Hospital, Institutes of Biomedical Science
- Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education
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Hamed MA, Ali SA. Non-viral factors contributing to hepatocellular carcinoma. World J Hepatol 2013; 5:311-322. [PMID: 23805355 PMCID: PMC3692972 DOI: 10.4254/wjh.v5.i6.311] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2013] [Revised: 05/10/2013] [Accepted: 05/18/2013] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a major cause of cancer death worldwide, accounting for over half a million deaths per year. The geographic pattern of HCC incidence is parallel to exposure to viral etiologic factors. Its incidence is increasing, ranging between 3% and 9% annually depending on the geographical location, and variability in the incidence rates correspond closely to the prevalence and pattern of the primary etiologic factors. Chronic infections with hepatitis B viruses or hepatitis C viruses have both been recognized as human liver carcinogens with a combined attributable fraction of at least 75% of all HCC cases. Multiple non-viral factors have been implicated in the development of HCC. Increased body mass index and diabetes with subsequent development of non-alcoholic steatohepatitis represent significant risk factors for HCC. Other non-viral causes of HCC include iron overload syndromes, alcohol use, tobacco, oral contraceptive, aflatoxin, pesticides exposure and betel quid chewing, a prevalent habit in the developing world. Wilson disease, α-1 antitrypsin deficiency, Porphyrias, autoimmune hepatitis, Schistosoma japonicum associated with positive hepatitis B surface antigen, and thorotrast-ray are also contributing hepatocellualar carcinoma. In addition, primary biliary cirrhosis, congestive liver disease and family history of liver cancer increase the risk of HCC incident. In conclusion, clarification of relevant non-viral causes of HCC will help to focus clinicians on those risk factors that are modifiable. The multilevel preventative approach will hopefully lead to a reduction in incidence of non-viral HCC, and a decrease in the patient morbidity and mortality as well as the societal economic burden associated with HCC.
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Affiliation(s)
- Manal A Hamed
- Manal A Hamed, Sanaa A Ali, Therapeutic Chemistry Department, Pharmaceutical and Drug Industries Division, National Research Centre, Dokki, Giza 12622, Egypt
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Abstract
Hepatocellular carcinoma (HCC) is a major cause of cancer death worldwide, accounting for over half a million deaths per year. The geographic pattern of HCC incidence is parallel to exposure to viral etiologic factors. Its incidence is increasing, ranging between 3% and 9% annually depending on the geographical location, and variability in the incidence rates correspond closely to the prevalence and pattern of the primary etiologic factors. Chronic infections with hepatitis B viruses or hepatitis C viruses have both been recognized as human liver carcinogens with a combined attributable fraction of at least 75% of all HCC cases. Multiple non-viral factors have been implicated in the development of HCC. Increased body mass index and diabetes with subsequent development of non-alcoholic steatohepatitis represent significant risk factors for HCC. Other non-viral causes of HCC include iron overload syndromes, alcohol use, tobacco, oral contraceptive, aflatoxin, pesticides exposure and betel quid chewing, a prevalent habit in the developing world. Wilson disease, α-1 antitrypsin deficiency, Porphyrias, autoimmune hepatitis, Schistosoma japonicum associated with positive hepatitis B surface antigen, and thorotrast-ray are also contributing hepatocellualar carcinoma. In addition, primary biliary cirrhosis, congestive liver disease and family history of liver cancer increase the risk of HCC incident. In conclusion, clarification of relevant non-viral causes of HCC will help to focus clinicians on those risk factors that are modifiable. The multilevel preventative approach will hopefully lead to a reduction in incidence of non-viral HCC, and a decrease in the patient morbidity and mortality as well as the societal economic burden associated with HCC.
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Affiliation(s)
- Manal A Hamed
- Manal A Hamed, Sanaa A Ali, Therapeutic Chemistry Department, Pharmaceutical and Drug Industries Division, National Research Centre, Dokki, Giza 12622, Egypt
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Mohamoud YA, Mumtaz GR, Riome S, Miller D, Abu-Raddad LJ. The epidemiology of hepatitis C virus in Egypt: a systematic review and data synthesis. BMC Infect Dis 2013; 13:288. [PMID: 23799878 PMCID: PMC3702438 DOI: 10.1186/1471-2334-13-288] [Citation(s) in RCA: 241] [Impact Index Per Article: 20.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2012] [Accepted: 06/19/2013] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Egypt has the highest prevalence of hepatitis C virus (HCV) in the world, estimated nationally at 14.7%. Our study's objective was to delineate the evidence on the epidemiology of HCV infection among the different population groups in Egypt, and to draw analytical inferences about the nature of HCV transmission in this country. METHODS We conducted a systematic review of all data on HCV prevalence and incidence in Egypt following PRISMA guidelines. The main sources of data included PubMed and Embase databases. We also used a multivariate regression model to infer the temporal trend of HCV prevalence among the general population and high risk population in Egypt. RESULTS We identified 150 relevant records, four of which were incidence studies. HCV incidence ranged from 0.8 to 6.8 per 1,000 person-years. Overall, HCV prevalence among pregnant women ranged between 5-15%, among blood donors between 5-25%, and among other general population groups between 0-40%. HCV prevalence among multi-transfused patients ranged between 10-55%, among dialysis patients between 50-90%, and among other high risk populations between 10% and 85%. HCV prevalence varied widely among other clinical populations and populations at intermediate risk. Risk factors appear to be parenteral anti-schistosomal therapy, injections, transfusions, and surgical procedures, among others. Results of our time trend analysis suggest that there is no evidence of a statistically significant decline in HCV prevalence over time in both the general population (p-value: 0.215) and high risk population (p-value: 0.426). CONCLUSIONS Egypt is confronted with an HCV disease burden of historical proportions that distinguishes this nation from others. A massive HCV epidemic at the national level must have occurred with substantial transmission still ongoing today. HCV prevention in Egypt must become a national priority. Policymakers, and public health and medical care stakeholders need to introduce and implement further prevention measures targeting the routes of HCV transmission.
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Affiliation(s)
- Yousra A Mohamoud
- Infectious Disease Epidemiology Group, Weill Cornell Medical College - Qatar, Cornell University, Qatar Foundation - Education City, Doha, Qatar
| | - Ghina R Mumtaz
- Infectious Disease Epidemiology Group, Weill Cornell Medical College - Qatar, Cornell University, Qatar Foundation - Education City, Doha, Qatar
| | - Suzanne Riome
- Infectious Disease Epidemiology Group, Weill Cornell Medical College - Qatar, Cornell University, Qatar Foundation - Education City, Doha, Qatar
| | - DeWolfe Miller
- Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, Hawaii
| | - Laith J Abu-Raddad
- Infectious Disease Epidemiology Group, Weill Cornell Medical College - Qatar, Cornell University, Qatar Foundation - Education City, Doha, Qatar
- Department of Public Health, Weill Cornell Medical College, Cornell University, New York, New York, USA
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
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Zeeneldin AA, Salem SE, Tabashy RH, Ibrahim AA, Alieldin NH. Transarterial chemoembolization for the treatment of hepatocellular carcinoma: a single center experience including 221 patients. J Egypt Natl Canc Inst 2013; 25:143-50. [PMID: 23932751 DOI: 10.1016/j.jnci.2013.05.003] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2013] [Revised: 05/20/2013] [Accepted: 05/20/2013] [Indexed: 01/16/2023] Open
Abstract
BACKGROUND Hepatocelluar carcinoma (HCC) is a major health problem in Egypt as well as in many countries. Transarterial chemoemoblization (TACE) is a treatment modality applicable to locally advanced HCC beyond surgery or ablative therapies and is associated with survival improvements. The aim of this study was to assess the outcomes of TACE in our center over the past four years. METHODS This is a retrospective cohort study that included 221 patients with locally advanced HCC treated with TACE in a single center between the years 2007 and 2010. The median age was 57 years with male predominance. Liver cirrhosis, viral hepatitis and Bilharziasis were encountered in 64%, 31% and 8% of patients, respectively. Abdominal pain was the most common presenting symptom (67%). Most cases were diagnosed based on radiology (57%) with a TNM stage I or II (73%) and a median AFP value of 150 ng/mL. RESULTS 221 patients received 440 cycles of TACE with a median of 2 cycles per patient. Cisplatin and doxorubicin (50mg per cycle, each) were the most commonly used drugs. Impaired liver function was the most common toxicity. Liver cell failure occurred in 17% of patients. An objective tumor response was achieved in 44% of cases. The median overall survival (OS) was 16 months (95% CI, 13-19 months) and the median progression free survival (PFS) was 6 months (95% CI, 4.3-7.8 months). Responding patients, Child-Pugh class A and patients receiving standard doses of chemotherapy had a significantly better OS than their counterparts. Only Child-Pugh class A was associated with significantly longer PFS (p < 0.001). CONCLUSION TACE produces reasonable responses and fair survival rates in locally advanced HCC but with noticeable toxicities. Proper patients' selection and prompt liver support are mandates for improving TACE outcomes.
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Schiefelbein E, Zekri AR, Newton DW, Soliman GA, Banerjee M, Hung CW, Seifeldin IA, Lo AC, Soliman AS. Hepatitis C virus and other risk factors in hepatocellular carcinoma. Acta Virol 2013; 56:235-40. [PMID: 23043603 DOI: 10.4149/av_2012_03_235] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
UNLABELLED Hepatocellular carcinoma (HCC) increased in Egypt in the past years, becoming the most common cancer among men. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the known primary risk factors for HCC. This study describes the viral profile of HCC in a predominantly rural area in Egypt. We included 148 HCC cases and 148 controls from the Tanta Cancer Center and the Gharbiah Cancer Society in the Nile delta region. Serological (ELISA) and molecular (PCR) analysis for HBV and HCV infection were performed on plasma samples from each subject. Epidemiologic, environmental, and medical histories were collected by interviewing of subjects. Around 90.5% of cases and controls were from rural areas. HCV infection was high in both cases and controls (89.2% and 49.3%, for cases and controls respectively by serology). HCV was the most important HCC risk factor [OR 9.7 (95% CI: 3.3-28.0, P <0.01)], and HBV infection showed marginal tendency of increased risk [OR 5.4 (95% CI: 0.9-31.8, P <0.06)]. Ever worked in farming [OR 2.8 (95% CI: 1.1-7.2, P <0.03)] and history of cirrhosis [OR 3.6 (95% CI: 1.6-8.1, P <0.01)] or blood transfusion [OR 4.2 (95% CI: 0.99-17.8, P <0.05)] were also associated with increased HCC risk. This study in a predominantly rural area in Egypt supports previous reports from other parts of Egypt that HCV infection is the primary HCC risk factor in Egypt. Further understanding of the relationship between infection and other risk factors in the development of HCC could lead to targeted interventions for at-risk individuals. KEYWORDS hepatocellular carcinoma; hepatitis; rural; risk factors; Egypt.
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Affiliation(s)
- E Schiefelbein
- Department of Epidemiology, Universit yof Michigan School of Public Health, Ann Arbor, Michigan, USA
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