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Xu JY, Yang YF, Huang ZY, Qian XY, Meng FH. Preoperative prediction of hepatocellular carcinoma microvascular invasion based on magnetic resonance imaging feature extraction artificial neural network. World J Gastrointest Surg 2024; 16:2546-2554. [PMID: 39220077 PMCID: PMC11362924 DOI: 10.4240/wjgs.v16.i8.2546] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Revised: 05/29/2024] [Accepted: 06/27/2024] [Indexed: 08/16/2024] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) recurrence is highly correlated with increased mortality. Microvascular invasion (MVI) is indicative of aggressive tumor biology in HCC. AIM To construct an artificial neural network (ANN) capable of accurately predicting MVI presence in HCC using magnetic resonance imaging. METHODS This study included 255 patients with HCC with tumors < 3 cm. Radiologists annotated the tumors on the T1-weighted plain MR images. Subsequently, a three-layer ANN was constructed using image features as inputs to predict MVI status in patients with HCC. Postoperative pathological examination is considered the gold standard for determining MVI. Receiver operating characteristic analysis was used to evaluate the effectiveness of the algorithm. RESULTS Using the bagging strategy to vote for 50 classifier classification results, a prediction model yielded an area under the curve (AUC) of 0.79. Moreover, correlation analysis revealed that alpha-fetoprotein values and tumor volume were not significantly correlated with the occurrence of MVI, whereas tumor sphericity was significantly correlated with MVI (P < 0.01). CONCLUSION Analysis of variable correlations regarding MVI in tumors with diameters < 3 cm should prioritize tumor sphericity. The ANN model demonstrated strong predictive MVI for patients with HCC (AUC = 0.79).
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Affiliation(s)
- Jing-Yi Xu
- Center of Hepatobiliary Pancreatic Disease, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
| | - Yu-Fan Yang
- Center of Hepatobiliary Pancreatic Disease, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
| | - Zhong-Yue Huang
- Department of Surgical, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
| | - Xin-Ye Qian
- Center of Hepatobiliary Pancreatic Disease, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
| | - Fan-Hua Meng
- Department of Anesthesiology, Huashan Hospital, Fudan University, Shanghai 200040, China
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Mottola M, Golfieri R, Bevilacqua A. The Effectiveness of an Adaptive Method to Analyse the Transition between Tumour and Peritumour for Answering Two Clinical Questions in Cancer Imaging. SENSORS (BASEL, SWITZERLAND) 2024; 24:1156. [PMID: 38400314 PMCID: PMC10893370 DOI: 10.3390/s24041156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 01/29/2024] [Accepted: 02/06/2024] [Indexed: 02/25/2024]
Abstract
Based on the well-known role of peritumour characterization in cancer imaging to improve the early diagnosis and timeliness of clinical decisions, this study innovated a state-of-the-art approach for peritumour analysis, mainly relying on extending tumour segmentation by a predefined fixed size. We present a novel, adaptive method to investigate the zone of transition, bestriding tumour and peritumour, thought of as an annular-like shaped area, and detected by analysing gradient variations along tumour edges. For method validation, we applied it on two datasets (hepatocellular carcinoma and locally advanced rectal cancer) imaged by different modalities and exploited the zone of transition regions as well as the peritumour ones derived by adopting the literature approach for building predictive models. To measure the zone of transition's benefits, we compared the predictivity of models relying on both "standard" and novel peritumour regions. The main comparison metrics were informedness, specificity and sensitivity. As regards hepatocellular carcinoma, having circular and regular shape, all models showed similar performance (informedness = 0.69, sensitivity = 84%, specificity = 85%). As regards locally advanced rectal cancer, with jagged contours, the zone of transition led to the best informedness of 0.68 (sensitivity = 89%, specificity = 79%). The zone of transition advantages include detecting the peritumour adaptively, even when not visually noticeable, and minimizing the risk (higher in the literature approach) of including adjacent diverse structures, which was clearly highlighted during image gradient analysis.
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Affiliation(s)
- Margherita Mottola
- Alma Mater Research Institute on Global Challenges and Climate Change (Alma Climate), University of Bologna, 40126 Bologna, Italy;
| | - Rita Golfieri
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138 Bologna, Italy;
| | - Alessandro Bevilacqua
- Department of Computer Science and Engineering (DISI), University of Bologna, 40126 Bologna, Italy
- Advanced Research Center on Electronic Systems (ARCES), University of Bologna, 40125 Bologna, Italy
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Zhang HD, Li XM, Zhang YH, Hu F, Tan L, Wang F, Jing Y, Guo DJ, Xu Y, Hu XL, Liu C, Wang J. Evaluation of Preoperative Microvascular Invasion in Hepatocellular Carcinoma Through Multidimensional Parameter Combination Modeling Based on Gd-EOB-DTPA MRI. J Clin Transl Hepatol 2023; 11:350-359. [PMID: 36643030 PMCID: PMC9817048 DOI: 10.14218/jcth.2021.00546] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 03/30/2022] [Accepted: 04/18/2022] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND AND AIMS The study established and compared the efficacy of the clinicoradiological model, radiomics model and clinicoradiological-radiomics hybrid model in predicting the microvascular invasion (MVI) of hepatocellular carcinoma (HCC) using gadolinium ethoxybenzyl diethylene triaminepentaacetic acid (Gd-EOB-DTPA) enhanced MRI. METHODS This was a study that enrolled 602 HCC patients from two institutions. Least absolute shrinkage and selection operator (Lasso) method was used to screen for the most important clinicoradiological and radiomics features that predict MVI pre-operatively. Three machine learning algorithms were used to establish the clinicoradiological, radiomics, and clinicoradiological-radiomics hybrid models. Area under the curve (AUC) of receiver operating characteristic (ROC) curves and Delong's test were used to compare and quantify the predictive performance of the models. RESULTS The AUCs of the clinicoradiological model in training and validation cohorts were 0.793 and 0.701, respectively. The radiomics signature of arterial phase (AP) images alone achieved satisfying predictive efficacy for MVI, with AUCs of 0.671 and 0.643 in training and validation cohort, respectively. The combination of clinicoradiological factors and fusion radiomics signature of AP and VP images achieved AUCs of 0.824 and 0.801 in training and validation cohorts, 0.812 and 0.805 in prospective validation and external validation cohorts, respectively. The hybrid model provided the best prediction results. The results of the Delong test revealed that there were statistically significant differences among the clinicoradiological-radiomics hybrid model, clinicoradiological model, and radiomics model (p<0.05). CONCLUSIONS The combination of clinicoradiological factors and fusion radiomics signature of AP and VP images based on Gd-EOB-DTPA-enhanced MRI can effectively predict MVI.
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Affiliation(s)
- Han-Dan Zhang
- Department of Radiology, Southwest Hospital, Third Military Medical University (Army Military Medical University), Chongqing, China
| | - Xiao-Ming Li
- Department of Radiology, Southwest Hospital, Third Military Medical University (Army Military Medical University), Chongqing, China
| | - Yu-Han Zhang
- Department of Radiology, Southwest Hospital, Third Military Medical University (Army Military Medical University), Chongqing, China
| | - Fang Hu
- Department of Radiology, Southwest Hospital, Third Military Medical University (Army Military Medical University), Chongqing, China
| | - Liang Tan
- Department of Neurosurgery, Third Military Medical University (Army Military Medical University), Chongqing, China
- Department of Electrical and Computer Engineering, Faculty of Science and Technology, University of Macau, Macau, China
| | - Fang Wang
- Department of Market, Huiying Medical Technology Co., Ltd, Beijing, China
| | - Yang Jing
- Department of Market, Huiying Medical Technology Co., Ltd, Beijing, China
| | - Da-Jing Guo
- Department of Radiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yang Xu
- Department of Radiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xian-Ling Hu
- Communication Sergeant School, Army Engineering University of PLA, Chongqing, China
| | - Chen Liu
- Department of Radiology, Southwest Hospital, Third Military Medical University (Army Military Medical University), Chongqing, China
- Correspondence to: Chen Liu and Jian Wang, Department of Radiology, Southwest Hospital, Third Military Medical University, Shazheng Street, Shapingba District, Chongqing 400038, China. ORCID: https://orcid.org/0000-0001-5149-2496 (CL) and https://orcid.org/0000-0003-1210-0837 (JW). Tel: +86-131-0896-8808 (CL) and +86-138-8378-5811 (JW), Fax: +86-23-6546-3026, E-mail: (CL) and (JW)
| | - Jian Wang
- Department of Radiology, Southwest Hospital, Third Military Medical University (Army Military Medical University), Chongqing, China
- Correspondence to: Chen Liu and Jian Wang, Department of Radiology, Southwest Hospital, Third Military Medical University, Shazheng Street, Shapingba District, Chongqing 400038, China. ORCID: https://orcid.org/0000-0001-5149-2496 (CL) and https://orcid.org/0000-0003-1210-0837 (JW). Tel: +86-131-0896-8808 (CL) and +86-138-8378-5811 (JW), Fax: +86-23-6546-3026, E-mail: (CL) and (JW)
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Zhang S, Duan C, Zhou X, Liu F, Wang X, Shao Q, Gao Y, Duan F, Zhao R, Wang G. Radiomics nomogram for prediction of microvascular invasion in hepatocellular carcinoma based on MR imaging with Gd-EOB-DTPA. Front Oncol 2022; 12:1034519. [PMID: 36387156 PMCID: PMC9663997 DOI: 10.3389/fonc.2022.1034519] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Accepted: 10/17/2022] [Indexed: 01/25/2023] Open
Abstract
OBJECTIVE To develop a radiomics nomogram for predicting microvascular invasion (MVI) before surgery in hepatocellular carcinoma (HCC) patients. MATERIALS AND METHODS The data from a total of 189 HCC patients (training cohort: n = 141; validation cohort: n = 48) were collected, involving the clinical data and imaging characteristics. Radiomics features of all patients were extracted from hepatobiliary phase (HBP) in 15 min. Least absolute shrinkage selection operator (LASSO) regression and logistic regression were utilized to reduce data dimensions, feature selection, and to construct a radiomics signature. Clinicoradiological factors were identified according to the univariate and multivariate analyses, which were incorporated into the final predicted nomogram. A nomogram was developed to predict MVI of HCC by combining radiomics signatures and clinicoradiological factors. Radiomics nomograms were evaluated for their discrimination capability, calibration, and clinical usefulness. RESULTS In the clinicoradiological factors, gender, alpha-fetoprotein (AFP) level, tumor shape and halo sign served as the independent risk factors of MVI, with which the area under the curve (AUC) is 0.802. Radiomics signatures covering 14 features at HBP 15 min can effectively predict MVI in HCC, to construct radiomics signature model, with the AUC of 0.732. In the final nomogram model the clinicoradiological factors and radiomics signatures were integrated, outperforming the clinicoradiological model (AUC 0.884 vs. 0.802; p <0.001) and radiomics signatures model (AUC 0.884 vs. 0.732; p < 0.001) according to Delong test results. A robust calibration and discrimination were demonstrated in the nomogram model. The results of decision curve analysis (DCA) showed more significantly clinical efficiency of the nomogram model in comparison to the clinicoradiological model and the radiomic signature model. CONCLUSIONS Depending on the clinicoradiological factors and radiological features on HBP 15 min images, nomograms can effectively predict MVI status in HCC patients.
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Affiliation(s)
- Shuai Zhang
- Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Chongfeng Duan
- Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xiaoming Zhou
- Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Fang Liu
- Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xin Wang
- Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Qiulin Shao
- Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yuanxiang Gao
- Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Feng Duan
- Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Ruirui Zhao
- Operating Room, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Gang Wang
- Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, China,*Correspondence: Gang Wang,
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Contrast-enhanced magnetic resonance imaging perfusion can predict microvascular invasion in patients with hepatocellular carcinoma (between 1 and 5 cm). ABDOMINAL RADIOLOGY (NEW YORK) 2022; 47:3264-3275. [PMID: 35113174 DOI: 10.1007/s00261-022-03423-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Revised: 01/12/2022] [Accepted: 01/12/2022] [Indexed: 01/18/2023]
Abstract
PURPOSE To evaluate the role of perfusion parameters with MR imaging of the liver in diagnosing MVI in hepatocellular carcinoma (HCC) (between 1 and 5 cm). MATERIALS AND METHODS This retrospective study was approved by the institutional review board. In 80 patients with 43 MVI( +) and 42 MVI( -) HCC, whole-liver perfusion MR imaging with Cartesian k-space undersampling and compressed sensing reconstruction was performed after injection of 0.1 mmol/kg gadopentetate dimeglumine. Parameters derived from a dual-input single-compartment model of arterial flow (Fa), portal venous flow (Fp), total blood flow (Ft = Fa + Fp), arterial fraction (ART), distribution volume (DV), and mean transit time (MTT) were measured. The significant parameters between the two groups were included to correlate with the presence of MVI at simple and multiple regression analysis. RESULTS In MVI-positive HCC, Fp was significantly higher than in MVI-negative HCC, whereas the reverse was seen for ART (p < 0.001). Tumor size (β = 1.2, p = 0.004; odds ratio, 3.20; 95% CI 1.45, 7.06), Fp (β = 1.1, p = 0.004; odds ratio, 3.09; 95% CI 1.42, 6.72), and ART (β = - 3.1, p = 0.001; odds ratio, 12.13; 95% CI 2.85, 51.49) were independent risk factors for MVI. The AUC value of the combination of all three metrics was 0.931 (95% CI 0.855, 0.975), with sensitivity of 97.6% and specificity of 76.2%. CONCLUSION The combination of Fp, ART, and tumor size demonstrated a higher diagnostic accuracy compared with each parameter used individually when evaluating MVI in HCC (between 1 and 5 cm).
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Atif M, Mustaan MA, Falak S, Ghaffar A, Munir B. Targeting the effect of sofosbuvir on selective oncogenes expression level of hepatocellular carcinoma Ras/Raf/MEK/ERK pathway in Huh7 cell line. Saudi J Biol Sci 2022; 29:103332. [PMID: 35813116 PMCID: PMC9256646 DOI: 10.1016/j.sjbs.2022.103332] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 04/21/2022] [Accepted: 05/29/2022] [Indexed: 11/29/2022] Open
Abstract
Direct acting antiviral agents are emerging line of treatment to eradicate Hepatitis C virus. Recent controversy over whether direct acting antiviral agents increase rate of hepatocellular carcinoma in HCV patients or prevent it, has increased the need to elaborate underlying mechanisms on molecular basis. This work was aimed to investigate the effect of sofosbuvir on the expression of selected oncogenes from the Ras/Raf/MEK/ERK pathway in Huh7 cell line. Results found concrete molecular evidence that sofosbuvir has significantly altered the expression of selected genes when huh7 cell line was treated with sofosbuvir. Nine genes related to HCC were found to be affected by sofosbuvir in a mixed effect manner. The relative expression of growth factors (VEGF, PDGFRB and HGF) was increased in sofosbuvir treated cell lines. The kinase family genes H-RAS, B-RAF, MET except MAPK1 were downregulated. Similarly, DUSP1 was upregulated and SPRY2 was slightly downregulated; both were negative feedback inhibitors of ERK signalling cascade. Sofosbuvir upregulated the growth factors and MAPK1 which suggests it to be a carcinogen. The downregulation of kinases and upregulation of DUSP1 make it an anticancer drug. Hence, the results from this study are important to prove that sofosbuvir neither reduce nor induce hepatocellular carcinoma.
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Affiliation(s)
- Muhammad Atif
- Department of Biochemistry, Government College University, Faisalabad 38000, Pakistan
| | | | - Sadia Falak
- Department of Biochemistry, University of Jhang, Jhang 35200, Pakistan
| | - Abdul Ghaffar
- Department of Biochemistry, Government College University, Faisalabad 38000, Pakistan
| | - Bushra Munir
- Institute of Chemistry, University of Sargodha, Sargodha 40100, Pakistan
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Jiang C, Zhao L, Xin B, Ma G, Wang X, Song S. 18F-FDG PET/CT radiomic analysis for classifying and predicting microvascular invasion in hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Quant Imaging Med Surg 2022; 12:4135-4150. [PMID: 35919043 PMCID: PMC9338369 DOI: 10.21037/qims-21-1167] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Accepted: 06/06/2022] [Indexed: 12/24/2022]
Abstract
Background Microvascular invasion (MVI) is a critical risk factor for early recurrence of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The aim of this study was to explore the contribution of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) radiomic features for the preoperative prediction of HCC and ICC classification and MVI. Methods In this retrospective study, 127 (HCC: ICC =76:51) patients with suspected MVI accompanied by either HCC or ICC were included (In HCC group, MVI positive: negative =46:30 in ICC group, MVI positive: negative =31:20). Results-driven feature engineering workflow was used to select the most predictive feature combinations. The prediction model was based on supervised machine learning classifier. Ten-fold cross validation on training cohort and independent test cohort were constructed to ensure stability and generalization ability of models. Results For HCC and ICC classification, radiomics predictors composed of two PET and one CT feature achieved area under the curve (AUC) of 0.86 (accuracy, sensitivity, specificity was 0.82, 0.78, 0.88, respectively) on test cohort. For MVI prediction, in HCC group, our MVI prediction model achieved AUC of 0.88 (accuracy, sensitivity, specificity was 0.78, 0.88, 0.60 respectively) with three PET features associated with tumor stage on test cohort. In ICC group, the phenotype composed of two PET features and carbohydrate antigen 19-9 (CA19-9) achieved AUC of 0.90 (accuracy, sensitivity, specificity was 0.77, 0.75, 0.80, respectively). Conclusions 18F-FDG PET/CT radiomic features integrating clinical factors have potential in HCC and ICC classification and MVI prediction, while PET features have dominant predictive power in model performance. The prediction model has value in providing a non-invasive biomarker for an earlier indication and comprehensive quantification of primary liver cancers.
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Affiliation(s)
- Chunjuan Jiang
- Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China
| | - Liwei Zhao
- School of Computer Science, The University of Sydney, Sydney, NSW, Australia
| | - Bowen Xin
- School of Computer Science, The University of Sydney, Sydney, NSW, Australia
| | - Guang Ma
- Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China
| | - Xiuying Wang
- School of Computer Science, The University of Sydney, Sydney, NSW, Australia
| | - Shaoli Song
- Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China
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The Transmission Route and Selection Pressure in HCV Subtype 3a and 3b Chinese Infections: Evolutionary Kinetics and Selective Force Analysis. Viruses 2022; 14:v14071514. [PMID: 35891494 PMCID: PMC9324606 DOI: 10.3390/v14071514] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Revised: 06/23/2022] [Accepted: 07/04/2022] [Indexed: 12/12/2022] Open
Abstract
Hepatitis C virus (HCV) genotype 3 (GT-3) represents 22–30% of all infections and is the second most common genotype among all HCV genotypes. It has two main subtypes, GT-3a and GT-3b, that present epidemiological differences in transmission groups. This report generated 56 GT-3a and 64 GT-3b whole-genome sequences to conduct an evolutionary kinetics and selective force analysis with reference sequences from various countries. Evolutionary analysis showed that HCV GT-3a worldwide might have been transmitted from the Indian subcontinent to South Asia, Europe, North America and then become endemic in China. In China, GT-3a may have been transmitted by intravenous drug users (IDUs) and become endemic in the general population, while GT-3b may have originated from IDUs and then underwent mutual transmission between blood donors (BDs) and IDUs, ultimately becoming independently endemic in IDUs. Furthermore, the spread of GT-3a and GT-3b sequences from BD and IDU populations exhibit different selective pressures: the proportion of positively selected sites (PPSs) in E1 and E2 from IDUs was higher than in BDs. The number of positive selection sites was higher in GT-3b and IDUs. These results indicate that different selective constraints act along with the GT-3a and GT-3b genomes from IDUs and BDs. In addition, GT-3a and GT-3b have different transmission routes in China, which allows us to formulate specific HCV prevention and control strategies in China.
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Salama II, Raslan HM, Abdel-Latif GA, Salama SI, Sami SM, Shaaban FA, Abdelmohsen AM, Fouad WA. Impact of direct-acting antiviral regimens on hepatic and extrahepatic manifestations of hepatitis C virus infection. World J Hepatol 2022; 14:1053-1073. [PMID: 35978668 PMCID: PMC9258264 DOI: 10.4254/wjh.v14.i6.1053] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Revised: 04/01/2022] [Accepted: 05/22/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) is a common cause of liver disease and is associated with various extrahepatic manifestations (EHMs). This mini-review outlines the currently available treatments for HCV infection and their prognostic effect on hepatic manifestations and EHMs. Direct-acting antiviral (DAA) regimens are considered pan-genotypic as they achieve a sustained virological response (SVR) > 85% after 12 wk through all the major HCV genotypes, with high percentages of SVR even in advanced fibrosis and cirrhosis. The risk factors for DAA failure include old males, cirrhosis, and the presence of resistance-associated substitutions (RAS) in the region targeted by the received DAAs. The effectiveness of DAA regimens is reduced in HCV genotype 3 with baseline RAS like A30K, Y93H, and P53del. Moreover, the European Association for the Study of the Liver recommended the identification of baseline RAS for HCV genotype 1a. The higher rate of hepatocellular carcinoma (HCC) after DAA therapy may be related to the fact that DAA regimens are offered to patients with advanced liver fibrosis and cirrhosis, where interferon was contraindicated to those patients. The change in the growth of pre-existing subclinical, undetectable HCC upon DAA treatment might be also a cause. Furthermore, after DAA therapy, the T cell-dependent immune response is much weaker upon HCV clearance, and the down-regulation of TNF-α or the elevated neutrophil to lymphocyte ratio might increase the risk of HCC. DAAs can result in reactivation of hepatitis B virus (HBV) in HCV co-infected patients. DAAs are effective in treating HCV-associated mixed cryoglobulinemia, with clinical and immunological responses, and have rapid and high effectiveness in thrombocytopenia. DAAs improve insulin resistance in 90% of patients, increase glomerular filtration rate, and decrease proteinuria, hematuria and articular manifestations. HCV clearance by DAAs allows a significant improvement in atherosclerosis and metabolic and immunological conditions, with a reduction of major cardiovascular events. They also improve physical function, fatigue, cognitive impairment, and quality of life. Early therapeutic approach with DAAs is recommended as it cure many of the EHMs that are still in a reversible stage and can prevent others that can develop due to delayed treatment.
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Affiliation(s)
- Iman Ibrahim Salama
- Department of Community Medicine Research, National Research Center, Giza 12622, Dokki, Egypt.
| | - Hala M Raslan
- Department of Internal Medicine, National Research Center, Giza 12622, Dokki, Egypt
| | - Ghada A Abdel-Latif
- Department of Community Medicine Research, National Research Center, Giza 12622, Dokki, Egypt
| | - Somaia I Salama
- Department of Community Medicine Research, National Research Center, Giza 12622, Dokki, Egypt
| | - Samia M Sami
- Department of Child Health, National Research Center, Giza 12622, Dokki, Egypt
| | - Fatma A Shaaban
- Department of Child Health, National Research Center, Giza 12622, Dokki, Egypt
| | - Aida M Abdelmohsen
- Department of Community Medicine Research, National Research Center, Giza 12622, Dokki, Egypt
| | - Walaa A Fouad
- Department of Community Medicine Research, National Research Center, Giza 12622, Dokki, Egypt
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Renzulli M, Mottola M, Coppola F, Cocozza MA, Malavasi S, Cattabriga A, Vara G, Ravaioli M, Cescon M, Vasuri F, Golfieri R, Bevilacqua A. Automatically Extracted Machine Learning Features from Preoperative CT to Early Predict Microvascular Invasion in HCC: The Role of the Zone of Transition (ZOT). Cancers (Basel) 2022; 14:cancers14071816. [PMID: 35406589 PMCID: PMC8997857 DOI: 10.3390/cancers14071816] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 03/18/2022] [Accepted: 03/31/2022] [Indexed: 02/08/2023] Open
Abstract
Background: Microvascular invasion (MVI) is a consolidated predictor of hepatocellular carcinoma (HCC) recurrence after treatments. No reliable radiological imaging findings are available for preoperatively diagnosing MVI, despite some progresses of radiomic analysis. Furthermore, current MVI radiomic studies have not been designed for small HCC nodules, for which a plethora of treatments exists. This study aimed to identify radiomic MVI predictors in nodules ≤3.0 cm by analysing the zone of transition (ZOT), crossing tumour and peritumour, automatically detected to face the uncertainties of radiologist’s tumour segmentation. Methods: The study considered 117 patients imaged by contrast-enhanced computed tomography; 78 patients were finally enrolled in the radiomic analysis. Radiomic features were extracted from the tumour and the ZOT, detected using an adaptive procedure based on local image contrast variations. After data oversampling, a support vector machine classifier was developed and validated. Classifier performance was assessed using receiver operating characteristic (ROC) curve analysis and related metrics. Results: The original 89 HCC nodules (32 MVI+ and 57 MVI−) became 169 (62 MVI+ and 107 MVI−) after oversampling. Of the four features within the signature, three are ZOT heterogeneity measures regarding both arterial and venous phases. On the test set (19MVI+ and 33MVI−), the classifier predicts MVI+ with area under the curve of 0.86 (95%CI (0.70–0.93), p∼10−5), sensitivity = 79% and specificity = 82%. The classifier showed negative and positive predictive values of 87% and 71%, respectively. Conclusions: The classifier showed the highest diagnostic performance in the literature, disclosing the role of ZOT heterogeneity in predicting the MVI+ status.
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Affiliation(s)
- Matteo Renzulli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy; (M.R.); (M.M.); (F.C.); (M.A.C.); (A.C.); (G.V.); (R.G.)
| | - Margherita Mottola
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy; (M.R.); (M.M.); (F.C.); (M.A.C.); (A.C.); (G.V.); (R.G.)
- Advanced Research Center on Electronic Systems (ARCES), University of Bologna, 40126 Bologna, Italy;
| | - Francesca Coppola
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy; (M.R.); (M.M.); (F.C.); (M.A.C.); (A.C.); (G.V.); (R.G.)
| | - Maria Adriana Cocozza
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy; (M.R.); (M.M.); (F.C.); (M.A.C.); (A.C.); (G.V.); (R.G.)
| | - Silvia Malavasi
- Advanced Research Center on Electronic Systems (ARCES), University of Bologna, 40126 Bologna, Italy;
| | - Arrigo Cattabriga
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy; (M.R.); (M.M.); (F.C.); (M.A.C.); (A.C.); (G.V.); (R.G.)
| | - Giulio Vara
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy; (M.R.); (M.M.); (F.C.); (M.A.C.); (A.C.); (G.V.); (R.G.)
| | - Matteo Ravaioli
- General Surgery and Transplant Unit, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Sant’Orsola-Malpighi Hospital, 40138 Bologna, Italy; (M.R.); (M.C.)
| | - Matteo Cescon
- General Surgery and Transplant Unit, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Sant’Orsola-Malpighi Hospital, 40138 Bologna, Italy; (M.R.); (M.C.)
| | - Francesco Vasuri
- Pathology Unit, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy;
| | - Rita Golfieri
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy; (M.R.); (M.M.); (F.C.); (M.A.C.); (A.C.); (G.V.); (R.G.)
| | - Alessandro Bevilacqua
- Advanced Research Center on Electronic Systems (ARCES), University of Bologna, 40126 Bologna, Italy;
- Department of Computer Science and Engineering (DISI), University of Bologna, 40126 Bologna, Italy
- Correspondence: ; Tel.: +39-05-1209-5409
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11
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Li X, Han X, Li L, Su C, Sun J, Zhan C, Feng D, Cheng W. Dynamic Contrast-Enhanced Ultrasonography with Sonazoid for Diagnosis of Microvascular Invasion in Hepatocellular Carcinoma. ULTRASOUND IN MEDICINE & BIOLOGY 2022; 48:575-581. [PMID: 34933756 DOI: 10.1016/j.ultrasmedbio.2021.11.005] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Revised: 10/30/2021] [Accepted: 11/08/2021] [Indexed: 06/14/2023]
Abstract
The aim of the present study was to investigate the imaging features observed in pre-operative Sonazoid contrast-enhanced ultrasound (SZ-CEUS) and the correlations with the presence of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients. In this single-center retrospective study, 31 patients with surgically and histopathologically confirmed HCC lesions were included. Patients were classified according to the presence of MVI into the MVI-positive group (n = 15) and MVI-negative group (n = 16). The CEUS examinations were performed within 2 or 3 d before surgery. Features, including tumor necrosis and ultrasound contrast agent (UCA) distribution characteristics in the arterial phase (AP), tumor types (single nodular [SN] or non-single nodular [non-SN]) in the post-vascular phase (PVP), wash-in time, wash-in slope, time to peak (TTP) and peak intensity (PI), were assessed. Univariate analysis revealed statistically significant differences between the two groups with respect to tumor necrosis (p = 0.002), inhomogeneous distribution of contrast agent in the AP (p = 0.001) and non-SN type in the PVP (p < 0.001). There was no significant difference in the quantitative parameters. Multivariate analysis revealed that non-SN type in the PVP was a significant independent risk factor for MVI of HCC (odds ratio = 30.51, 95% confidence interval [CI]: 2.335-398.731, p = 0.009). The area under the receiver operating characteristic (ROC) curve (AUC), sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 0.873, 93.3%, 81.3%, 82.4% and 92.9%, respectively. Thus, SZ-CEUS can provide useful information for the diagnosis of MVI in HCC.
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Affiliation(s)
- Xintong Li
- Department of Ultrasound, Hepatology, and Pathology, Harbin Medical University Cancer Hospital, Nangang District, Harbin, PR China
| | - Xue Han
- Department of Ultrasound, Hepatology, and Pathology, Harbin Medical University Cancer Hospital, Nangang District, Harbin, PR China
| | - Lei Li
- Department of Ultrasound, Hepatology, and Pathology, Harbin Medical University Cancer Hospital, Nangang District, Harbin, PR China
| | - Chang Su
- Department of Ultrasound, Hepatology, and Pathology, Harbin Medical University Cancer Hospital, Nangang District, Harbin, PR China
| | - Jianmin Sun
- Department of Ultrasound, Hepatology, and Pathology, Harbin Medical University Cancer Hospital, Nangang District, Harbin, PR China
| | - Chao Zhan
- Department of Ultrasound, Hepatology, and Pathology, Harbin Medical University Cancer Hospital, Nangang District, Harbin, PR China
| | - Di Feng
- Department of Ultrasound, Hepatology, and Pathology, Harbin Medical University Cancer Hospital, Nangang District, Harbin, PR China
| | - Wen Cheng
- Department of Ultrasound, Hepatology, and Pathology, Harbin Medical University Cancer Hospital, Nangang District, Harbin, PR China.
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12
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Kamal A, Elsheaita A, Abdelnabi M. Association between direct-acting antiviral agents in hepatitis C virus treatment and hepatocellular carcinoma occurrence and recurrence: The endless debate. World J Clin Cases 2022; 10:1764-1774. [PMID: 35317156 PMCID: PMC8891795 DOI: 10.12998/wjcc.v10.i6.1764] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Revised: 08/05/2021] [Accepted: 01/26/2022] [Indexed: 02/06/2023] Open
Abstract
Since direct-acting antiviral agents (DAAs) have been introduced into hepatitis C virus treatment, the sustained viral response (SVR) rate has significantly increased to more than 95%. Scientific evidence supports the idea that SVR after interferon therapy has beneficial effects related to cirrhosis progression, resulting in a reduction in the incidence of hepatocellular carcinoma (HCC). However, a significant debate exists related to DAA impact on HCC development. We reviewed the current literature highlighting the controversial data related to DAA association with de novo HCC occurrence or recurrence and possible pathophysiology of HCC related to DAAs. After a review of the published literature, we believe that the current evidence does not confirm or repudiate a higher rate of de novo HCC occurrence or recurrence related to DAA therapy. More trials are needed to determine if there is an association between HCC occurrence or recurrence and DAA or if it is related to preexisting liver cirrhosis.
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Affiliation(s)
- Ahmed Kamal
- Internal Medicine Department, Faculty of Medicine Alexandria University, Alexandria 21131, Egypt
| | - Ahmed Elsheaita
- Clinical and Experimental Internal Medicine Department, Medical Research Institute Alexandria University, Alexandria 21561, Egypt
| | - Mahmoud Abdelnabi
- Clinical and Experimental Internal Medicine Department, Medical Research Institute Alexandria University, Alexandria 21561, Egypt
- Internal Medicine Department, Texas Tech University Health Science Center, Lubbock, TX 79430, United States
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13
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Gömer A, Brown RJP, Pfaender S, Deterding K, Reuter G, Orton R, Seitz S, Bock CT, Cavalleri JMV, Pietschmann T, Wedemeyer H, Steinmann E, Todt D. Intra-host analysis of hepaciviral glycoprotein evolution reveals signatures associated with viral persistence and clearance. Virus Evol 2022; 8:veac007. [PMID: 35242360 PMCID: PMC8887644 DOI: 10.1093/ve/veac007] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 01/28/2022] [Accepted: 01/31/2022] [Indexed: 11/13/2022] Open
Abstract
Even 30 years after the discovery of the hepatitis C virus (HCV) in humans there is still no vaccine available. Reasons for this include the high mutation rate of HCV, which allows the virus to escape immune recognition and the absence of an immunocompetent animal model for vaccine development. Phylogenetically distinct hepaciviruses (genus Hepacivirus, family Flaviviridae) have been isolated from diverse species, each with a narrow host range: the equine hepacivirus (EqHV) is the closest known relative of HCV. In this study, we used amplicon-based deep-sequencing to investigate the viral intra-host population composition of the genomic regions encoding the surface glycoproteins E1 and E2. Patterns of E1E2 substitutional evolution were compared in longitudinally sampled EqHV-positive sera of naturally and experimentally infected horses and HCV-positive patients. Intra-host virus diversity was higher in chronically than in acutely infected horses, a pattern which was similar in the HCV-infected patients. However, overall glycoprotein variability was higher in HCV compared to EqHV. Additionally, selection pressure in HCV populations was higher, especially within the N-terminal region of E2, corresponding to the hypervariable region 1 (HVR1) in HCV. An alignment of glycoprotein sequences from diverse hepaciviruses identified the HVR1 as a unique characteristic of HCV: hepaciviruses from non-human species lack this region. Together, these data indicate that EqHV infection of horses could represent a powerful surrogate animal model to gain insights into hepaciviral evolution and HCVs HVR1-mediated immune evasion strategy.
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Affiliation(s)
- André Gömer
- Department for Molecular and Medical Virology, Ruhr University Bochum, Universitätsstr. 150, Bochum 44801, Germany
- Institute of Virology, University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, Hannover 30559, Germany
| | - Richard J P Brown
- Division of Veterinary Medicine, Paul Ehrlich Institute, Paul-Ehrlich-Straße 51-59, Langen 63225, Germany
| | - Stephanie Pfaender
- Department for Molecular and Medical Virology, Ruhr University Bochum, Universitätsstr. 150, Bochum 44801, Germany
| | - Katja Deterding
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg-Straße 1, Hannover 30625, Germany
- German Center for Infectious Disease Research (DZIF), HepNet Study-House, Hannover 30625, Germany
| | - Gábor Reuter
- Department of Medical Microbiology and Immunology, Medical School, University of Pécs, Szigeti út 12., Pécs 7624, Hungary
| | - Richard Orton
- MRC-University of Glasgow, Centre for Virus Research, Garscube Campus, 464 Bearsden Road, Glasgow G61 1QH, United Kingdom
| | - Stefan Seitz
- Department of Infectious Diseases, Molecular Virology, University of Heidelberg, Heidelberg 69120, Germany
| | - C- Thomas Bock
- Division of Viral Gastroenteritis and Hepatitis Pathogens and Enteroviruses, Department of Infectious Diseases, Robert Koch Institute, Berlin 13353, Germany
| | - Jessika M V Cavalleri
- Clinical Unit of Equine Internal Medicine, University of Veterinary Medicine Vienna, Veterinärplatz 1, Vienna 1210, Austria
| | - Thomas Pietschmann
- Twincore, Centre for Experimental and Clinical Infection Research, Institute of Experimental Virology, Hannover 30625, Germany
- German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig Site, Hannover 30625, Germany
- Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover 30625, Germany
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg-Straße 1, Hannover 30625, Germany
- German Center for Infectious Disease Research (DZIF), HepNet Study-House, Hannover 30625, Germany
| | - Eike Steinmann
- Department for Molecular and Medical Virology, Ruhr University Bochum, Universitätsstr. 150, Bochum 44801, Germany
| | - Daniel Todt
- Department for Molecular and Medical Virology, Ruhr University Bochum, Universitätsstr. 150, Bochum 44801, Germany
- Twincore, Centre for Experimental and Clinical Infection Research, Institute of Experimental Virology, Hannover 30625, Germany
- European Virus Bioinformatics Centre (EVBC), Jena 07743, Germany
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14
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Elbaz T, Waked I, El-Akel W, Shaker MK, Abdelaziz AO, Yousif M, El-Bendary M, Zaky S, AbdAllah M, Hassany M, Esmat G, Doss W. Impact of successful HCV treatment using direct acting antivirals on recurrence of well ablated hepatocellular carcinoma. Expert Rev Anti Infect Ther 2022; 20:307-314. [PMID: 34253123 DOI: 10.1080/14787210.2021.1951230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Accepted: 06/30/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND There are many contradictory studies that dealt with hepatocellular carcinoma (HCC) recurrence rate of well ablated hepatitis C virus (HCV) related HCC. We aim to assess the recurrence rate of previously ablated HCC in patients who received direct acting antiviral (DAA) for their HCV. RESEARCH DESIGN AND METHODS This is a retrospective data analysis of 523 HCV patients who have a history of successfully ablated HCC and eligible for HCV treatment. Retrieval was done to demographic/clinical data, HCV pretreatment investigations, HCV treatment outcome. Follow up for survival and HCC recurrence was done every 3 months using abdominal ultrasound and alfa-fetoprotein. RESULTS Mean age was 53.83 years. Sofosbuvir/daclatasvir/ribavirin was the most used regimen (35.4%) with 438 patients (83.7%) achieved sustained virologic response (SVR). The median duration for surveillance was 159 weeks. Hundred and five patients developed recurrent HCC, with a crude recurrence rate of 20.1%. There was no difference between HCV responders and non-responders in crude recurrence rate (p = 0.94) but HCC developed earlier in non-responders (p = <0.01). CONCLUSION Recurrence of HCC remains a threat in HCV patients even after achieving an SVR. Implementation of long-term surveillance programs is highly recommended.
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Affiliation(s)
- Tamer Elbaz
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Imam Waked
- Department of Hepatology, National Liver Institute, Menoufiya University, Menoufiya, Egypt
| | - Wafaa El-Akel
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed Kamal Shaker
- Tropical Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | | | - Monkez Yousif
- Internal Medicine Department, Zagazig University, Sharkia, Egypt
| | - Mahmoud El-Bendary
- Department of Tropical Medicine and Hepatology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Samy Zaky
- Department of Hepatogastroenterology and Infectious Diseases, Al-Azhar University, Cairo, Egypt
| | - Mohamed AbdAllah
- Medical Research Division, National Research Center, Giza, Egypt
| | - Mohamed Hassany
- Tropical Medicine Department, National Hepatology & Tropical Medicine Research Institute, Cairo, Egypt
| | - Gamal Esmat
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Wahid Doss
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
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15
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Renzulli M, Peta G, Vasuri F, Marasco G, Caretti D, Bartalena L, Spinelli D, Giampalma E, D'Errico A, Golfieri R. Standardization of conventional chemoembolization for hepatocellular carcinoma. Ann Hepatol 2021; 22:100278. [PMID: 33129978 DOI: 10.1016/j.aohep.2020.10.006] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Accepted: 10/19/2020] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVES Conventional transarterial chemoembolization (cTACE) has several limitations due to the lack of standardization. The aim of this study was to evaluate the chemical and physical characteristics and behaviors over time of emulsions for cTACE and to assess intra- and inter-operator variabilities in the preparation processes. MATERIALS AND METHODS This in vitro study involved evaluation of emulsions for cTACE prepared using two methods: water-in-oil (WiO) and chemotherapeutic-in-oil (CiO). Three emulsions were prepared with each method and obtained after 20, 50, and 100 pumping exchanges. A drop from each final mixture was analyzed via light microscopy (time 1) and after 5, 10, 15, and 20min since the end of preparation. After 20min, all preparations were re-mixed and new drops were re-evaluated. The intra- and inter-operator variabilities were analyzed. RESULTS The mean droplet diameter decreased non-significantly when the number of pumping exchanges increased and increased significantly over time for both WiO and CiO. The droplets returned to their initial diameters after re-mixing. There were no significant differences in the intra- and inter-operator variabilities (P>0.01). CONCLUSIONS Any interventional radiologist, regardless of their experience, may prepare these emulsions. These data may represent a set of instructions to standardize cTACE.
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Affiliation(s)
- Matteo Renzulli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna, Italy.
| | - Giuliano Peta
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna, Italy
| | - Francesco Vasuri
- Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna, Italy
| | - Giovanni Marasco
- Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna, Italy
| | - Daniele Caretti
- "Toso Montanari" Industrial Chemistry Department, University of Bologna, Bologna, Italy
| | - Laura Bartalena
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna, Italy
| | - Daniele Spinelli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna, Italy
| | | | - Antonietta D'Errico
- Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna, Italy
| | - Rita Golfieri
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna, Italy
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16
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Fouad M, El Kassas M, Ahmed E, El Sheemy R. Tumor characteristics of hepatocellular carcinoma after direct-acting antiviral treatment for hepatitis C: Comparative analysis with antiviral therapy-naive patients. World J Hepatol 2021; 13:1743-1752. [PMID: 34904042 PMCID: PMC8637672 DOI: 10.4254/wjh.v13.i11.1743] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Revised: 06/30/2021] [Accepted: 09/29/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Insufficient and contradictory data are available about the relation between direct-acting antivirals (DAAs) and hepatocellular carcinoma (HCC) development in patients with hepatitis C virus (HCV). AIM To analyze differences in basic clinical, radiological, and laboratory characteristics in addition to tumor behavior upon HCC diagnosis between patients with and without a previous history of DAAs exposure. METHODS This multicenter case-control study included 497 patients with chronic HCV-related HCC, allocated into one of two groups according to their history of antiviral treatment for their HCV. RESULTS Group I included 151 HCC patients with a history of DAAs, while 346 patients who had never been treated with DAAs were assigned to group II. A significant difference was observed between both groups regarding basic assessment scores (Child, MELD, and BCLC), which tended to have more advanced liver disease and HCC stage upon diagnosis in group I. However, serum albumin was significantly affected, and serum α-fetoprotein was significantly higher in group II (P < 0.001). In addition, group I showed significant HCC multicentricity than group II, while the incidence of portal vein thrombosis was significantly higher in group I (P < 0.001). CONCLUSION The basic clinical scores and laboratory characteristics of HCC patients are advanced in patients who are naïve to DAAs treatment; however, HCC behavior is more aggressive in DAA-treated patients.
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Affiliation(s)
- Magdy Fouad
- Department of Tropical Medicine and Gastroenterology, Minia University, Minia 61519, Egypt
| | - Mohamed El Kassas
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo 11795, Egypt.
| | - Elham Ahmed
- Department of Internal Medicine, Minia University, Minia 61519, Egypt
| | - Reem El Sheemy
- Department of Tropical Medicine, Minia University, Minia 61111, Egypt
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17
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Elbahrawy A, Ibrahim MK, Eliwa A, Alboraie M, Madian A, Aly HH. Current situation of viral hepatitis in Egypt. Microbiol Immunol 2021; 65:352-372. [PMID: 33990999 DOI: 10.1111/1348-0421.12916] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 05/02/2021] [Accepted: 05/11/2021] [Indexed: 12/12/2022]
Abstract
An estimated 8-10 million people suffer from viral hepatitis in Egypt. Hepatitis A virus (HAV) and hepatitis E virus (HEV) are the major causes of viral hepatitis in Egypt as 50% or more of the Egyptian population are already exposed to HAV infection by the age of 15. In addition, over 60% of the Egyptian population test seropositive for anti-HEV in the first decade of life. HEV mainly causes self-limiting hepatitis; however, cases of fulminant hepatitis and liver failure were reported in Egypt. Hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis D virus (HDV) are the main causes of chronic hepatitis, liver cirrhosis, and liver cancer (hepatocellular carcinoma [HCC]) in Egypt. Globally, Egypt had the highest age-standardized death rate due to cirrhosis from 1990 to 2017. The prevalence rate of HBV (1.3%-1.5%) has declined after national infantile immunization. Coinfection of HBV patients with HDV is common in Egypt because HDV antibodies (IgG) vary in range from 8.3% to 43% among total HBV patients. After the conduction of multiple national programs to control HCV infection, a lower rate of HCV prevalence (4.6%) was recently reported. Data about the incidence of HCV after treatment with direct antiviral agents (DAAs) are lacking. An HCC incidence of 29/1000/year in cirrhotic patients after DAA treatment is reported. A higher rate of infiltrative pattern among HCC patients after DAA treatment is also recognized. Viral hepatitis is one of the major public health concerns in Egypt that needs more attention and funding from health policymakers.
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Affiliation(s)
- Ashraf Elbahrawy
- Department of Internal Medicine, Al-Azhar University, Cairo, Egypt
| | - Marwa K Ibrahim
- Department of Microbial Biotechnology, Division of Genetic Engineering and Biotechnology Research, National Research Centre, Giza, Egypt
- Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
| | - Ahmed Eliwa
- Department of Internal Medicine, Al-Azhar University, Cairo, Egypt
| | - Mohamed Alboraie
- Department of Internal Medicine, Al-Azhar University, Cairo, Egypt
| | - Ali Madian
- Department of Internal Medicine, Al-Azhar University, Assiut, Egypt
| | - Hussein Hassan Aly
- Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
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18
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Muzica CM, Stanciu C, Cijevschi-Prelipcean C, Girleanu I, Huiban L, Petrea OC, Singeap AM, Cojocariu C, Cuciureanu T, Sfarti C, Zenovia S, Chriac S, Stefanescu G, Ciortescu I, Lupașcu-Ursulescu C, Miftode E, Trifan A. Long-term Risk of Hepatocellular Carcinoma Following Direct-Acting Antiviral Therapy in Compensated Liver Cirrhosis Induced by Hepatitis C Virus Infection. HEPATITIS MONTHLY 2021; 21. [DOI: 10.5812/hepatmon.115910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
Background: Considering the excellent safety profile and the high efficacy rates, great benefits were expected with the availability of the new direct-acting antivirals (DAAs) in treating hepatitis C virus (HCV) infection. Following the publication of two articles in 2016 on the high incidence rates of hepatocelullar carcinoma (HCC) following DAAs, several papers revealed contradictory results, thereby casting shadows on the role of DAAs in hepatocarcinogenesis. Objectives: The present study aimed to assess the incidence and risk factors of HCC in patients with HCV genotype 1b infection and compensated cirrhosis with the sustained virological response (SVR) following DAAs. Methods: This multicentric prospective study encompassed 479 patients with HCV genotype 1b compensated cirrhosis treated with paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD) +/- ribavirin (RBV) for 12 weeks in two tertiary centers in Northeastern Romania. The patients were prospectively followed up in the Institute of Gastroenterology Iasi, Romania, from November 2015 to December 2020. Results: During the follow-up period (mean 60.11 ± 3.87 months), 23 patients (4.8%) developed HCC. The 1-, 3-, and 5-year cumulative incidence rates of HCC were 1.1, 1.9, and 2.6%, respectively. At the time of the diagnosis, 15 patients (65%) had a single tumor, 12 patients (52.2%) were within the Milan criteria, and nine persons (39%) had Barcelona liver cancer stage 0-A. In this regard, the mean AFP level was 35.3 ± 93.1 ng/mL. A multivariate analysis, age above 65 years, and a cutoff point of AFP ≥ 10 ng/mL at the end of treatment were independent factors associated with HCC. A majority of the patients (n = 11, 47.8%) received curative treatment by surgical resection. In this study, histopathological examination identified a moderately differentiated tumor (G2) in 5 patients, five patients had a poorly differentiated tumor (G3), and only one patient had a well-differentiated tumor (G1). Conclusions: Our study revealed no evidence of the high incidence rate of HCC after the long-term follow-up of patients with HCV-related liver cirrhosis and SVR following DAA treatment. However, the cumulative 5-year risk remained above the cutoff point, and this makes the HCC screening cost-effective. The HCC occurrence appears to be associated with aging and a moderately increased AFP level at EOT (≥ 10 ng/mL).
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19
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Montasser IF, Ibrahim AA, Farid HM, Al Balakosy AM. De novo hepatocellular carcinoma in cirrhotic hepatitis C virus: Are directly acting antivirals beneficial? Clin Res Hepatol Gastroenterol 2021; 45:101517. [PMID: 32900667 DOI: 10.1016/j.clinre.2020.07.022] [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: 05/19/2020] [Revised: 07/28/2020] [Accepted: 07/28/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIM Behavior of HCC that developed after DAAs therapy for HCV infection is still debated. In this study we aim to compare characteristics and pattern of de novo HCC in cirrhotic HCV patients who were treated and untreated with DAAs. PATIENTS AND METHODS This study included 160 cirrhotic HCV patients presented with de novo HCC during the period of December 2017 to December 2018. Patients were divided into two groups, group A included 80 patients who received DAAs and group B included 80 patients who were not exposed to DAAs. The characteristics of HCC in both groups were compared using BCLC Staging System. RESULTS The size of the largest lesion was 47mm±26 in group A and 41mm±27 in group B with statistically significant difference between both groups (p=0.03). No other significant differences existed regarding number, site, or total tumor size and most of the lesions were solid in both groups. Portal vein thrombosis and extrahepatic spread detected in 16 and 11 patients in group A, while in group B the number was 17 and 9 patients respectively (p=0.83 and 0.06). No significant differences between groups in type of intervention done, BCLC staging (p=0.4), or survival. CONCLUSION Although CHCV patients treated with DAAs had larger de novo HCC lesions than untreated patients, there was no difference in BCLC staging or in aggressive behavior between both groups.
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Affiliation(s)
- Iman F Montasser
- Department of Tropical Medicine, Faculty of Medicine - Ain Shams University, Cairo, Egypt.
| | - Amany A Ibrahim
- Department of Tropical Medicine, Faculty of Medicine - Ain Shams University, Cairo, Egypt.
| | - Hoda M Farid
- Department of Tropical Medicine, Faculty of Medicine - Ain Shams University, Cairo, Egypt.
| | - Amira M Al Balakosy
- Department of Tropical Medicine, Faculty of Medicine - Ain Shams University, Cairo, Egypt.
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Pre-transplant Psoas Muscle Density as a Ready-to-Use and Low-cost Predictor of Patient Survival After Liver Transplant. HEPATITIS MONTHLY 2021. [DOI: 10.5812/hepatmon.99690] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
Background: Sarcopenia, defined as low muscle mass with reduced function, is frequently encountered in cirrhotic patients and is a major predictor of adverse events, including post-liver transplant (LT) outcome. Objectives: This study assessed the impact of sarcopenia using computed tomography (CT)-based measurements on post-LT mortality and complications. Methods: From January 2008 to June 2016, 646 adult patients underwent 613 LTs at our institution. We analyzed the postoperative outcome of 287 patients who had pathologically proven cirrhosis on the explanted liver and who had performed a CT examination three months before LT. Psoas muscle density (PMD) was detected for every patient using standard instruments present in the radiological workstation and was related to postoperative survival rates and complications. Statistical analysis was carried out using the appropriate tests. Results: Postoperative mortality was 6.3%. At least one grade III-IV postoperative complication was experienced by 121 patients. Respiratory and infective complications occurred in 30 and 32 patients, respectively. Also, PMD was an independent predictor of postoperative mortality (P = 0.021), respiratory complications (P = 0.015), and infections (P = 0.010). The ROC analysis identified a PMD ≤ 43.72 HU as the best cutoff value for predicting 90-day mortality after LT. Conclusions: Psoas muscle density accurately predicted post-LT mortality and complications. Its ease and low-cost determination can allow widespread use of this parameter to improve clinical care and help with the decision to give these patients some priority on the transplant waiting list.
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Prediction of Microvascular Invasion in Hepatocellular Carcinoma via Deep Learning: A Multi-Center and Prospective Validation Study. Cancers (Basel) 2021; 13:cancers13102368. [PMID: 34068972 PMCID: PMC8156235 DOI: 10.3390/cancers13102368] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 05/06/2021] [Accepted: 05/09/2021] [Indexed: 02/05/2023] Open
Abstract
Simple Summary Microvascular invasion (MVI) is an independent risk factor for postoperative recurrence of hepatocellular carcinoma (HCC). Preoperative knowledge of MVI would assist with tailored surgical strategy making to prolong patient survival. Previous radiological studies proved the role of noninvasive medical imaging in MVI prediction. However, hitherto, deep learning methods remained unexplored for this clinical task. As an end-to-end self-learning strategy, deep learning may not only achieve improved prediction accuracy, but may also visualize high-risk areas of invasion by generating attention maps. In this multicenter study, we developed deep learning models to perform MVI preoperative assessments using two imaging modalities—computed tomography (CT) and gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI). A head-to-head prospective validation was conducted to verify the validity of deep learning models and achieve a comparison between CT and EOB-MRI for MVI assessment. The findings put forward a better understanding of MVI preoperative prediction in HCC management. Abstract Microvascular invasion (MVI) is a critical risk factor for postoperative recurrence of hepatocellular carcinoma (HCC). Preknowledge of MVI would assist tailored surgery planning in HCC management. In this multicenter study, we aimed to explore the validity of deep learning (DL) in MVI prediction using two imaging modalities—contrast-enhanced computed tomography (CE-CT) and gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI). A total of 750 HCCs were enrolled from five Chinese tertiary hospitals. Retrospective CE-CT (n = 306, collected between March, 2013 and July, 2019) and EOB-MRI (n = 329, collected between March, 2012 and March, 2019) data were used to train two DL models, respectively. Prospective external validation (n = 115, collected between July, 2015 and February, 2018) was performed to assess the developed models. Furthermore, DL-based attention maps were utilized to visualize high-risk MVI regions. Our findings revealed that the EOB-MRI-based DL model achieved superior prediction outcome to the CE-CT-based DL model (area under receiver operating characteristics curve (AUC): 0.812 vs. 0.736, p = 0.038; sensitivity: 70.4% vs. 57.4%, p = 0.015; specificity: 80.3% vs. 86.9%, p = 0.052). DL attention maps could visualize peritumoral high-risk areas with genuine histopathologic confirmation. Both DL models could stratify high and low-risk groups regarding progression free survival and overall survival (p < 0.05). Thus, DL can be an efficient tool for MVI prediction, and EOB-MRI was proven to be the modality with advantage for MVI assessment than CE-CT.
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Jiang YQ, Cao SE, Cao S, Chen JN, Wang GY, Shi WQ, Deng YN, Cheng N, Ma K, Zeng KN, Yan XJ, Yang HZ, Huan WJ, Tang WM, Zheng Y, Shao CK, Wang J, Yang Y, Chen GH. Preoperative identification of microvascular invasion in hepatocellular carcinoma by XGBoost and deep learning. J Cancer Res Clin Oncol 2021; 147:821-833. [PMID: 32852634 PMCID: PMC7873117 DOI: 10.1007/s00432-020-03366-9] [Citation(s) in RCA: 98] [Impact Index Per Article: 24.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Accepted: 08/18/2020] [Indexed: 02/06/2023]
Abstract
PURPOSE Microvascular invasion (MVI) is a valuable predictor of survival in hepatocellular carcinoma (HCC) patients. This study developed predictive models using eXtreme Gradient Boosting (XGBoost) and deep learning based on CT images to predict MVI preoperatively. METHODS In total, 405 patients were included. A total of 7302 radiomic features and 17 radiological features were extracted by a radiomics feature extraction package and radiologists, respectively. We developed a XGBoost model based on radiomics features, radiological features and clinical variables and a three-dimensional convolutional neural network (3D-CNN) to predict MVI status. Next, we compared the efficacy of the two models. RESULTS Of the 405 patients, 220 (54.3%) were MVI positive, and 185 (45.7%) were MVI negative. The areas under the receiver operating characteristic curves (AUROCs) of the Radiomics-Radiological-Clinical (RRC) Model and 3D-CNN Model in the training set were 0.952 (95% confidence interval (CI) 0.923-0.973) and 0.980 (95% CI 0.959-0.993), respectively (p = 0.14). The AUROCs of the RRC Model and 3D-CNN Model in the validation set were 0.887 (95% CI 0.797-0.947) and 0.906 (95% CI 0.821-0.960), respectively (p = 0.83). Based on the MVI status predicted by the RRC and 3D-CNN Models, the mean recurrence-free survival (RFS) was significantly better in the predicted MVI-negative group than that in the predicted MVI-positive group (RRC Model: 69.95 vs. 24.80 months, p < 0.001; 3D-CNN Model: 64.06 vs. 31.05 months, p = 0.027). CONCLUSION The RRC Model and 3D-CNN models showed considerable efficacy in identifying MVI preoperatively. These machine learning models may facilitate decision-making in HCC treatment but requires further validation.
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Affiliation(s)
- Yi-Quan Jiang
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, 510630, Guangdong, China
| | - Su-E Cao
- Department of Radiology, The Third Affiliated Hospital, Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, 510630, China
| | - Shilei Cao
- Tencent Youtu Lab, Malata Building, Kejizhongyi Road, Nanshan District, Shenzhen, 518075, China
| | - Jian-Ning Chen
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, 510630, China
| | - Guo-Ying Wang
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, 510630, Guangdong, China
| | - Wen-Qi Shi
- Department of Radiology, The Third Affiliated Hospital, Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, 510630, China
| | - Yi-Nan Deng
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, 510630, Guangdong, China
| | - Na Cheng
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, 510630, China
| | - Kai Ma
- Tencent Youtu Lab, Malata Building, Kejizhongyi Road, Nanshan District, Shenzhen, 518075, China
| | - Kai-Ning Zeng
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, 510630, Guangdong, China
| | - Xi-Jing Yan
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, 510630, Guangdong, China
| | - Hao-Zhen Yang
- Tencent Healthcare, Tengxun Building, Kejizhongyi Road, Nanshan District, Shenzhen, 518075, China
| | - Wen-Jing Huan
- Tencent Healthcare, Tengxun Building, Kejizhongyi Road, Nanshan District, Shenzhen, 518075, China
| | - Wei-Min Tang
- Tencent Healthcare, Tengxun Building, Kejizhongyi Road, Nanshan District, Shenzhen, 518075, China
| | - Yefeng Zheng
- Tencent Youtu Lab, Malata Building, Kejizhongyi Road, Nanshan District, Shenzhen, 518075, China
| | - Chun-Kui Shao
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, 510630, China
| | - Jin Wang
- Department of Radiology, The Third Affiliated Hospital, Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, 510630, China
| | - Yang Yang
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, 510630, Guangdong, China.
| | - Gui-Hua Chen
- Organ Transplantation Research Center of Guangdong Province, Guangzhou, 510630, Guangdong, China.
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital, Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, 510630, Guangdong, China.
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Kamal A, Elmoety AAA, Rostom YA, Shater MS, Lashen SA. Hepatocellular carcinoma recurrence after directly acting antivirals for chronic hepatitis C: a 2-year follow-up study. Clin Exp Hepatol 2021; 7:66-73. [PMID: 34027117 PMCID: PMC8122091 DOI: 10.5114/ceh.2021.104397] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Accepted: 11/20/2020] [Indexed: 02/06/2023] Open
Abstract
AIM OF THE STUDY Data regarding hepatocellular carcinoma (HCC) recurrence after directly acting antivirals for hepatitis C are contradictory. Our aim was to study the HCC recurrence in patients who received directly acting antivirals after tumor ablation. MATERIAL AND METHODS This retrospective study included all Child-Pugh A and B patients with hepatitis C related < 5 cm single or up to 3 HCC without any vascular or extrahepatic involvement whose lesions were managed using microwave or radiofrequency ablation at the Internal Medicine Department of Alexandria Faculty of Medicine, in the period from 1 January 2016 to 31 December 2016, and then received directly acting antivirals. RESULTS Data from 52 patients were analyzed. Throughout the 2 years from ablation, 42.3% of patients experienced tumor recurrence (22 out of 52 patients). In addition, two subjects died and 4 subjects were lost to follow-up before any tumor recurrence. CONCLUSIONS Although our study included both modified Child-Pugh A and B patients and included lesions up to 5 cm treated using thermal ablation, the 2-year HCC recurrence rate was similar to that previously reported after surgical resection or radiofrequency ablation of lesions up to 3 cm in Child-Pugh A patients before development of directly acting antivirals.
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Affiliation(s)
- Ahmed Kamal
- Hepatology Unit, Internal Medicine Department, Alexandria University, Egypt
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Mangoud NOM, Ali SA, El Kassas M, Soror SH. Chitinase 3-like-1, Tolloid-like protein 1, and intergenic gene polymorphisms are predictors for hepatocellular carcinoma development after hepatitis C virus eradication by direct-acting antivirals. IUBMB Life 2021; 73:474-482. [PMID: 33347699 DOI: 10.1002/iub.2444] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Revised: 12/19/2020] [Accepted: 12/20/2020] [Indexed: 02/02/2023]
Abstract
Hepatocellular carcinoma (HCC) is a major cause of cancer death in Egypt. There is still a risk for HCC development even after eradicating hepatitis C virus (HCV) by direct-acting antivirals (DAAs). Chitinase-3-like-protein-1 (CHI3L1), a biomarker for predicting many diseases, plays an essential role in inflammation, angiogenesis, and antiapoptosis. Tolloid-like protein 1 (TLL1) may be involved in hepatic fibrogenesis and carcinogenesis. This study aimed to determine the role and combined effect of CHI3L1 (rs880633), TLL1 (rs1503298), and an intergenic (rs597533) polymorphisms on the risk of developing HCC in Egyptian patients after achieving sustained virological response (SVR) by DAAs. Blood samples were collected from 68 HCC patients, 77 non-HCC subjects, and 80 healthy controls. The DNA was extracted and analyzed for rs880633, rs1503298, and rs597533 using Genotyping TaqMan™ assay. The result of the present study showed a significant difference in genotypes and alleles frequencies in both (rs880633) and (rs597533) in HCC group as compared to healthy control and also as compared to the non-HCC group. However, regarding to (rs1503298) genotypes and alleles between the HCC and non-HCC groups, there were no significant differences. Combined polymorphism in more than one gene simultaneously showed a higher risk to HCC after SVR than an individual locus. Both allelic and genotypic variations of the CHI3L1 gene (rs880633) and an intergenic (rs597533) seemed to be significant predictors confirming a great risk for HCC susceptibility in Egyptian patients achieved SVR. Patients with a polymorphism in more than one gene showed an increased risk to HCC after SVR rather than individual locus.
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Affiliation(s)
- Nadia O M Mangoud
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy, Helwan University, Helwan, Egypt
| | - Sahar A Ali
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy, Helwan University, Helwan, Egypt
| | - Mohamed El Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Helwan, Egypt
| | - Sameh H Soror
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy, Helwan University, Helwan, Egypt
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Sawatzki M, Güller U, Güsewell S, Husarik DB, Semela D, Brand S. Contrast-enhanced ultrasound can guide the therapeutic strategy by improving the detection of colorectal liver metastases. J Hepatol 2021; 74:419-427. [PMID: 33065168 DOI: 10.1016/j.jhep.2020.09.036] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Revised: 09/14/2020] [Accepted: 09/17/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS CT may miss up to 30% of cases of colorectal liver metastases (CRLMs). We assessed the impact of contrast-enhanced ultrasound (CEUS) on the detection of CRLMs and on changes to the therapeutic strategy; additionally, we assessed the accuracy of CEUS in differentiating unclear focal liver lesions (FLLs) compared to staging-CT. METHODS We prospectively analyzed all patients with newly diagnosed and histologically confirmed colorectal cancer (CRC) at our tertiary gastroenterological center between December 2015 and May 2019. CEUS was performed in a total of 296 patients without CRLMs after staging-CT using the contrast agent (SonoVue®). Standard of reference was obtained by MRI or histology to diagnose CRLMs missed by CT. Benign FLLs were confirmed by MRI or follow-up CT (mean follow-up interval: 18 months). RESULTS Eight additional CRLMs were detected by CEUS (overall 2.7%; sensitivity 88.9%, specificity 99.0%, positive predictive value 100%, negative predictive value 99.6%). All patients with CRLMs detected only by CEUS were in tumor stage T3/T4 (4.0% additionally detected CRLMs). The number needed to screen to detect 1 additional CRLM by CEUS was 37 in all patients and 24.5 in T3/T4-patients. When results were reviewed by a board-certified radiologist and oncologist, the therapeutic strategy changed in 6 of these 8 patients. Among the 62 patients (20.9%) with unclear FLLs after staging-CT, CEUS determined the dignity (malignant vs. benign) of 98.4% of the FLLs. CONCLUSION Overall, CEUS detected 2.7% additional CRLMs (including 4.0% in tumor stage T3/T4) with a significant impact on the oncological therapeutic strategy for 75% of these patients. Patients with tumor stage T3/T4 would particularly benefit from CEUS. We propose CEUS as the first imaging modality for CT-detected lesions of unknown dignity. LAY SUMMARY In patients with newly diagnosed colorectal cancer, contrast-enhanced ultrasound (CEUS) detected additional liver metastases after computed tomography (CT). In the majority of these patients, the oncological therapy was changed after obtaining the CEUS results. After staging-CT, 21% of hepatic lesions remained unclear. In these cases, CEUS was accurate to either reveal or exclude liver metastasis in nearly all patients and could reduce costs (e.g., number of MRI scans).
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Affiliation(s)
- Mikael Sawatzki
- Department of Gastroenterology and Hepatology, Kantonsspital, St. Gallen, Switzerland.
| | - Ulrich Güller
- Center for Medical Oncology & Hematology, Spital STS Thun, Switzerland; Clinic for Visceral Surgery and Medicine, Inselspital, University of Bern, Bern, Switzerland
| | - Sabine Güsewell
- Clinical Trials Unit, Kantonsspital, St. Gallen, Switzerland
| | - Daniela B Husarik
- Institute of Radiology and Nuclear Medicine, Kantonsspital, St. Gallen, Switzerland
| | - David Semela
- Department of Gastroenterology and Hepatology, Kantonsspital, St. Gallen, Switzerland
| | - Stephan Brand
- Department of Gastroenterology and Hepatology, Kantonsspital, St. Gallen, Switzerland
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Radiomics Analysis of MR Imaging with Gd-EOB-DTPA for Preoperative Prediction of Microvascular Invasion in Hepatocellular Carcinoma: Investigation and Comparison of Different Hepatobiliary Phase Delay Times. BIOMED RESEARCH INTERNATIONAL 2021; 2021:6685723. [PMID: 33506029 PMCID: PMC7810556 DOI: 10.1155/2021/6685723] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Accepted: 12/23/2020] [Indexed: 12/14/2022]
Abstract
Purpose To investigate whether the radiomics analysis of MR imaging in the hepatobiliary phase (HBP) can be used to predict microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC). Method A total of 130 patients with HCC, including 80 MVI-positive patients and 50 MVI-negative patients, who underwent MR imaging with Gd-EOB-DTPA were enrolled. Least absolute shrinkage and selection operator (LASSO) regression was applied to select radiomics parameters derived from MR images obtained in the HBP 5 min, 10 min, and 15 min images. The selected features at each phase were adopted into support vector machine (SVM) classifiers to establish models. Multiple comparisons of the AUCs at each phase were performed by the Delong test. The decision curve analysis (DCA) was used to analyze the classification of MVI-positive and MVI-negative patients. Results The most predictive features between MVI-positive and MVI-negative patients included 9, 8, and 14 radiomics parameters on HBP 5 min, 10 min, and 15 min images, respectively. A model incorporating the selected features produced an AUC of 0.685, 0.718, and 0.795 on HBP 5 min, 10 min, and 15 min images, respectively. The predictive model for HBP 5 min, 10 min and 15 min showed no significant difference by the Delong test. DCA indicated that the predictive model for HBP 15 min outperformed the models for HBP 5 min and 10 min. Conclusions Radiomics parameters in the HBP can be used to predict MVI, with the HBP 15 min model having the best differential diagnosis ability.
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Direct Antiviral Treatments for Hepatitis C Virus Have Off-Target Effects of Oncologic Relevance in Hepatocellular Carcinoma. Cancers (Basel) 2020; 12:cancers12092674. [PMID: 32961688 PMCID: PMC7565876 DOI: 10.3390/cancers12092674] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 09/14/2020] [Accepted: 09/15/2020] [Indexed: 12/25/2022] Open
Abstract
Simple Summary Hepatitis C virus (HCV) eradication by direct-acting antiviral agents (DAAs) reduces de novo hepatocellular carcinoma incidence in cirrhosis; however, contrasting evidence on higher incidence of hepatocellular carcinoma (HCC) was reported in patients previously treated for HCC. Here, we showed that sofosbuvir and daclatasvir can modulate cell proliferation, invasion capability and gene expression in HCC-derived cell lines, suggesting that off-target effects of these drugs might be responsible for both the increase and reduction of cell proliferation and migration capability. Off-target gene modulation, mainly affecting mitochondrial functions, ribosomal genes and histones, was consistent with matched phenotypic changes and might account either for pro-oncogenic or tumor-suppressive functions of DAAs, that seemed to be dictated by the molecular background. Abstract Background and Aims: HCV eradication by direct-acting antiviral agents (DAAs) reduces de novo hepatocellular carcinoma (HCC) incidence in cirrhosis; however, contrasting evidence about beneficial or detrimental effects still exists in patients who have already developed HCC. Methods: we investigated whether sofosbuvir and daclatasvir modulate cell proliferation, invasion capability and gene expression (RNA-seq) in HCC-derived cell lines, hypothesizing possible off-target effects of these drugs. Results observed in HCC cell lines were validated in non-HCC cancer-derived cell lines and a preliminary series of human HCC tissues by qPCR and IHC. Results: DAAs can affect HCC cell proliferation and migration capability by either increasing or reducing them, showing transcriptomic changes consistent with some unexpected drug-associated effects. Off-target gene modulation, mainly affecting ribosomal genes, mitochondrial functions and histones, points to epigenetics and proliferation as relevant events, consistent with matched phenotypic changes. A preliminary validation of in vitro findings was performed in a restricted cohort of HCC patients previously treated with DAAs, with immunohistochemical correlations suggesting DAA-treated HCCs to be more aggressive in terms of migration and epidermal-to-mesenchymal transition. Conclusions: Our findings suggested the possible occurrence of off-target effects ultimately modulating cell proliferation and/or migration and potentially justified previous findings showing some instances of particularly aggressive HCC recurrence as well as reduced incidence of recurrence of HCC following treatment with DAAs.
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Sangiovanni A, Alimenti E, Gattai R, Filomia R, Parente E, Valenti L, Marzi L, Pellegatta G, Borgia G, Gambato M, Terreni N, Serio I, Belli L, Oliveri F, Maimone S, Brunacci M, D'Ambrosio R, Forzenigo LV, Russo FP, Rumi M, Barone M, Fracanzani AL, Raimondo G, Giannini EG, Brunetto MR, Villa E, Biganzoli E, Colombo M, Lampertico P. Undefined/non-malignant hepatic nodules are associated with early occurrence of HCC in DAA-treated patients with HCV-related cirrhosis. J Hepatol 2020; 73:593-602. [PMID: 32243959 DOI: 10.1016/j.jhep.2020.03.030] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Revised: 03/16/2020] [Accepted: 03/17/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIM An unexpected early increase in incidence, recurrence and clinical aggressiveness of hepatocellular carcinoma (HCC) has been reported (and refuted) in patients with HCV-related cirrhosis following direct-acting antiviral (DAA) treatment. To address this controversy, we performed a prospective multicenter study on consecutively enrolled cirrhotic patients, with or without a history of HCC, undergoing DAA therapy. PATIENTS AND METHODS A total of 1,161 HCC-free cirrhotics (group 1) and 124 cirrhotics who had received a curative treatment for an HCC (group 2) were enrolled. Clinical features, including presence of undefined/non-malignant liver nodules (UNMNs), were analyzed with respect to HCC incidence and recurrence. RESULTS During a median study time of 17 months in group 1 and 16 months in group 2, de novo HCC developed in 48 patients (yearly incidence 3.1/100 patient-years, 75% BCLC 0-A) and recurred in 40 (mean yearly incidence 29.9/100 patient-years, 83% BCLC 0-A). A peak of HCC instant incidence was observed at 4.2 months in group 1 patients with UNMNs, and at 7.7 months in group 2. By multivariable Cox regression models, UNMNs (hazard ratio [HR] 3.11; 95% CI 1.47-6.57: p = 0.003), ascites detected any time before enrolment (HR 3.04; 95% CI 1.23-7.51; p = 0.02), and alpha-fetoprotein log-value (HR 1.90; 95% CI 1.05-3.44; p = 0.03) were the variables independently associated with the incidence of de novo HCC, while history of alcohol abuse (HR 2.10; 95% CI 1.08-4.09; p = 0.03) and history of recurrence of HCC (HR 2.87; 95% CI 1.35-6.09; p = 0.006) were associated with HCC recurrence. CONCLUSION An early high incidence of both de novo HCC, in patients with UNMNs, and recurrent HCC was observed in DAA-treated patients; this was not accompanied by increased tumor aggressiveness. LAY SUMMARY This prospective study focuses on the risk of developing de novo or recurrent hepatocellular carcinoma (HCC) after direct-acting antiviral (DAA) treatment in patients with hepatitis C-related cirrhosis. We found that DAA treatment was associated with an early high HCC incidence in patients with undefined or non-malignant nodules, as well as in those with a history of complete response to HCC treatment. Whether this is related to the presence of clinically undetectable nests of cancer cells or to precancerous lesions that may progress to overt HCC upon DAA treatment remains unanswered. No evidence of increased clinical aggressiveness was reported in de novo or recurrent HCC.
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Affiliation(s)
- Angelo Sangiovanni
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico - Division of Gastroenterology and Hepatology - CRC "A. M. and A. Migliavacca" Center for Liver Disease, Milan, Italy.
| | - Eleonora Alimenti
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico - Division of Gastroenterology and Hepatology - CRC "A. M. and A. Migliavacca" Center for Liver Disease, Milan, Italy
| | - Riccardo Gattai
- Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, University Hospital of Pisa, Pisa, Italy
| | - Roberto Filomia
- Division of Clinical and Molecular Hepatology, University Hospital of Messina, Messina, Italy
| | - Elisabetta Parente
- Gastroenterology Unit, Department of Emergency and Organ Transplantation (D.E.T.O.), University of Bari, Bari, Italy
| | - Luca Valenti
- Internal Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Luca Marzi
- Gastroenterology Unit, Azienda Ospedaliero-Universitaria Policlinico di Modena, Modena, Italy
| | - Gaia Pellegatta
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Guglielmo Borgia
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples 'Federico II', Naples, Italy
| | - Martina Gambato
- Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padua University Hospital, Padua, Italy
| | | | - Ilaria Serio
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Luca Belli
- UOC Epatologia e Gastroenterologia, Ospedale Niguarda, Milan, Italy
| | - Filippo Oliveri
- Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, University Hospital of Pisa, Pisa, Italy
| | - Sergio Maimone
- Division of Clinical and Molecular Hepatology, University Hospital of Messina, Messina, Italy
| | - Matteo Brunacci
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Roberta D'Ambrosio
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico - Division of Gastroenterology and Hepatology - CRC "A. M. and A. Migliavacca" Center for Liver Disease, Milan, Italy
| | | | - Francesco Paolo Russo
- Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Mariagrazia Rumi
- Division of Hepatology, Ospedale San Giuseppe, Università degli Studi di Milano, Milan, Italy
| | - Michele Barone
- Gastroenterology Unit, Department of Emergency and Organ Transplantation (D.E.T.O.), University of Bari, Bari, Italy
| | - Anna Ludovica Fracanzani
- Internal Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Giovanni Raimondo
- Division of Clinical and Molecular Hepatology, University Hospital of Messina, Messina, Italy
| | | | - Maurizia Rossana Brunetto
- Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, University Hospital of Pisa, Pisa, Italy; Internal Medicine, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Erica Villa
- Gastroenterology Unit, Azienda Ospedaliero-Universitaria Policlinico di Modena, Modena, Italy
| | - Elia Biganzoli
- Department of Clinical Sciences and Community Health & DSRC, University of Milan, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Massimo Colombo
- Center of Translational Research in Hepatology, Humanitas Hospital, Rozzano, Italy
| | - Pietro Lampertico
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico - Division of Gastroenterology and Hepatology - CRC "A. M. and A. Migliavacca" Center for Liver Disease, Milan, Italy; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
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Renzulli M, Clemente A, Spinelli D, Ierardi AM, Marasco G, Farina D, Brocchi S, Ravaioli M, Pettinari I, Cescon M, Reginelli A, Cappabianca S, Carrafiello G, Golfieri R. Gastric Cancer Staging: Is It Time for Magnetic Resonance Imaging? Cancers (Basel) 2020; 12:1402. [PMID: 32485933 PMCID: PMC7352169 DOI: 10.3390/cancers12061402] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2020] [Revised: 05/17/2020] [Accepted: 05/28/2020] [Indexed: 12/13/2022] Open
Abstract
Gastric cancer (GC) is a common cancer worldwide. Its incidence and mortality vary depending on geographic area, with the highest rates in Asian countries, particularly in China, Japan, and South Korea. Accurate imaging staging has become crucial for the application of various treatment strategies, especially for curative treatments in early stages. Unfortunately, most GCs are still diagnosed at an advanced stage, with the peritoneum (61-80%), distant lymph nodes (44-50%), and liver (26-38%) as the most common metastatic locations. Metastatic disease is limited to the peritoneum in 58% of cases; in nonperitoneal distant metastases, the most involved GC metastasization site is the liver (82%). The eighth edition of the tumor-node-metastasis staging system is the most commonly used system for determining GC prognosis. Endoscopic ultrasonography, computed tomography, and 18-fluorideoxyglucose positron emission tomography are historically the most accurate imaging techniques for GC staging. However, studies have recently shown renewed interest in magnetic resonance imaging (MRI) as a useful tool in GC staging, especially for distant metastasis assessment. The technical improvement of diffusion-weighted imaging and the increasing use of hepatobiliary contrast agents have been shown to increase the diagnostic performance of MRI, particularly for detecting peritoneal and liver metastasis. However, no principal oncological guidelines have included the use of MRI as a first-line technique for distant metastasis evaluation during the GC staging process, such as the National Comprehensive Cancer Network Guidelines. This review analyzed the role of the principal imaging techniques in GC diagnosis and staging, focusing on the potential role of MRI, especially for assessing peritoneal and liver metastases.
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Affiliation(s)
- Matteo Renzulli
- Radiology Unit, Department of Experimental, Diagnostic and Speciality Medicine, Sant’Orsola Hospital, University of Bologna, 40138 Bologna, Italy; (D.S.); (S.B.); (I.P.); (R.G.)
| | - Alfredo Clemente
- Radiology and Radiotherapy Unit, Department of Precision Medicine, University of Campania “L. Vanvitelli”, 80138 Naples, Italy; (A.C.); (A.R.); (S.C.)
| | - Daniele Spinelli
- Radiology Unit, Department of Experimental, Diagnostic and Speciality Medicine, Sant’Orsola Hospital, University of Bologna, 40138 Bologna, Italy; (D.S.); (S.B.); (I.P.); (R.G.)
| | - Anna Maria Ierardi
- Diagnostic and Interventional Radiology, ASST Santi Paolo e Carlo, San Paolo Hospital, 20142 Milan, Italy; (A.M.I.); (G.C.)
| | - Giovanni Marasco
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy;
| | - Davide Farina
- Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, 25138 Brescia, Italy;
| | - Stefano Brocchi
- Radiology Unit, Department of Experimental, Diagnostic and Speciality Medicine, Sant’Orsola Hospital, University of Bologna, 40138 Bologna, Italy; (D.S.); (S.B.); (I.P.); (R.G.)
| | - Matteo Ravaioli
- General and Transplant Surgery Unit, Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; (M.R.); (M.C.)
| | - Irene Pettinari
- Radiology Unit, Department of Experimental, Diagnostic and Speciality Medicine, Sant’Orsola Hospital, University of Bologna, 40138 Bologna, Italy; (D.S.); (S.B.); (I.P.); (R.G.)
| | - Matteo Cescon
- General and Transplant Surgery Unit, Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; (M.R.); (M.C.)
| | - Alfonso Reginelli
- Radiology and Radiotherapy Unit, Department of Precision Medicine, University of Campania “L. Vanvitelli”, 80138 Naples, Italy; (A.C.); (A.R.); (S.C.)
| | - Salvatore Cappabianca
- Radiology and Radiotherapy Unit, Department of Precision Medicine, University of Campania “L. Vanvitelli”, 80138 Naples, Italy; (A.C.); (A.R.); (S.C.)
| | - Gianpaolo Carrafiello
- Diagnostic and Interventional Radiology, ASST Santi Paolo e Carlo, San Paolo Hospital, 20142 Milan, Italy; (A.M.I.); (G.C.)
| | - Rita Golfieri
- Radiology Unit, Department of Experimental, Diagnostic and Speciality Medicine, Sant’Orsola Hospital, University of Bologna, 40138 Bologna, Italy; (D.S.); (S.B.); (I.P.); (R.G.)
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Bojkova D, Westhaus S, Costa R, Timmer L, Funkenberg N, Korencak M, Streeck H, Vondran F, Broering R, Heinrichs S, Lang KS, Ciesek S. Sofosbuvir Activates EGFR-Dependent Pathways in Hepatoma Cells with Implications for Liver-Related Pathological Processes. Cells 2020; 9:cells9041003. [PMID: 32316635 PMCID: PMC7225999 DOI: 10.3390/cells9041003] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Revised: 04/10/2020] [Accepted: 04/13/2020] [Indexed: 12/12/2022] Open
Abstract
Direct acting antivirals (DAAs) revolutionized the therapy of chronic hepatitis C infection. However, unexpected high recurrence rates of hepatocellular carcinoma (HCC) after DAA treatment became an issue in patients with advanced cirrhosis and fibrosis. In this study, we aimed to investigate an impact of DAA treatment on the molecular changes related to HCC development and progression in hepatoma cell lines and primary human hepatocytes. We found that treatment with sofosbuvir (SOF), a backbone of DAA therapy, caused an increase in EGFR expression and phosphorylation. As a result, enhanced translocation of EGFR into the nucleus and transactivation of factors associated with cell cycle progression, B-MYB and Cyclin D1, was detected. Serine/threonine kinase profiling identified additional pathways, especially the MAPK pathway, also activated during SOF treatment. Importantly, the blocking of EGFR kinase activity by erlotinib during SOF treatment prevented all downstream events. Altogether, our findings suggest that SOF may have an impact on pathological processes in the liver via the induction of EGFR signaling. Notably, zidovudine, another nucleoside analogue, exerted a similar cell phenotype, suggesting that the observed effects may be induced by additional members of this drug class.
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Affiliation(s)
- Denisa Bojkova
- Institute of Virology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany; (D.B.); (S.W.); (R.C.); (L.T.); (N.F.)
- Institute of Medical Virology, University Hospital, Goethe University Frankfurt am Main, 60590 Frankfurt, Germany
| | - Sandra Westhaus
- Institute of Virology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany; (D.B.); (S.W.); (R.C.); (L.T.); (N.F.)
- Institute of Medical Virology, University Hospital, Goethe University Frankfurt am Main, 60590 Frankfurt, Germany
| | - Rui Costa
- Institute of Virology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany; (D.B.); (S.W.); (R.C.); (L.T.); (N.F.)
| | - Lejla Timmer
- Institute of Virology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany; (D.B.); (S.W.); (R.C.); (L.T.); (N.F.)
| | - Nora Funkenberg
- Institute of Virology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany; (D.B.); (S.W.); (R.C.); (L.T.); (N.F.)
| | - Marek Korencak
- Institute for HIV research, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany; (M.K.); (H.S.)
| | - Hendrik Streeck
- Institute for HIV research, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany; (M.K.); (H.S.)
| | - Florian Vondran
- Clinic for General, Abdominal and Transplant Surgery, Hannover Medical School, 30625 Hannover, Germany;
- German Center for Infection Research (DZIF), 45147 Essen, Germany
| | - Ruth Broering
- Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany;
| | - Stefan Heinrichs
- Institute for Transfusion Medicine, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany;
| | - Karl S Lang
- Institute of Immunology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany;
| | - Sandra Ciesek
- Institute of Virology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany; (D.B.); (S.W.); (R.C.); (L.T.); (N.F.)
- Institute of Medical Virology, University Hospital, Goethe University Frankfurt am Main, 60590 Frankfurt, Germany
- German Center for Infection Research (DZIF), 45147 Essen, Germany
- Correspondence: ; Tel.: +49-69-63015219
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Dash S, Aydin Y, Widmer KE, Nayak L. Hepatocellular Carcinoma Mechanisms Associated with Chronic HCV Infection and the Impact of Direct-Acting Antiviral Treatment. J Hepatocell Carcinoma 2020; 7:45-76. [PMID: 32346535 PMCID: PMC7167284 DOI: 10.2147/jhc.s221187] [Citation(s) in RCA: 73] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Accepted: 03/06/2020] [Indexed: 12/12/2022] Open
Abstract
Hepatitis C virus (HCV) infection is the major risk factor for liver cirrhosis and hepatocellular carcinoma (HCC). The mechanisms of HCC initiation, growth, and metastasis appear to be highly complex due to the decade-long interactions between the virus, immune system, and overlapping bystander effects of host metabolic liver disease. The lack of a readily accessible animal model system for HCV is a significant obstacle to understand the mechanisms of viral carcinogenesis. Traditionally, the primary prevention strategy of HCC has been to eliminate infection by antiviral therapy. The success of virus elimination by antiviral treatment is determined by the SVR when the HCV is no longer detectable in serum. Interferon-alpha (IFN-α) and its analogs, pegylated IFN-α (PEG-IFN-α) alone with ribavirin (RBV), have been the primary antiviral treatment of HCV for many years with a low cure rate. The cloning and sequencing of HCV have allowed the development of cell culture models, which accelerated antiviral drug discovery. It resulted in the selection of highly effective direct-acting antiviral (DAA)-based combination therapy that now offers incredible success in curing HCV infection in more than 95% of all patients, including those with cirrhosis. However, several emerging recent publications claim that patients who have liver cirrhosis at the time of DAAs treatment face the risk of HCC occurrence and recurrence after viral cure. This remains a substantial challenge while addressing the long-term benefit of antiviral medicine. The host-related mechanisms that drive the risk of HCC in the absence of the virus are unknown. This review describes the multifaceted mechanisms that create a tumorigenic environment during chronic HCV infection. In addition to the potential oncogenic programming that drives HCC after viral clearance by DAAs, the current status of a biomarker development for early prediction of cirrhosis regression and HCC detection post viral treatment is discussed. Since DAAs treatment does not provide full protection against reinfection or viral transmission to other individuals, the recent studies for a vaccine development are also reviewed.
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Affiliation(s)
- Srikanta Dash
- Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, New Orleans, LA70112, USA
- Southeast Louisiana Veterans Health Care System, New Orleans, LA70119, USA
- Department of Medicine, Division of Gastroenterology, Tulane University Health Sciences Center, New Orleans, LA70112, USA
| | - Yucel Aydin
- Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, New Orleans, LA70112, USA
| | - Kyle E Widmer
- Southeast Louisiana Veterans Health Care System, New Orleans, LA70119, USA
| | - Leela Nayak
- Southeast Louisiana Veterans Health Care System, New Orleans, LA70119, USA
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Renzulli M, Tovoli F, Clemente A, Ierardi AM, Pettinari I, Peta G, Marasco G, Festi D, Piscaglia F, Cappabianca S, Carrafiello G, Golfieri R. Ablation for hepatocellular carcinoma: beyond the standard indications. Med Oncol 2020; 37:23. [PMID: 32166482 DOI: 10.1007/s12032-020-01348-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Accepted: 02/20/2020] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma (HCC), the most common primary liver neoplasia, represents the fifth most common malignant disease in men. Percutaneous ablation treatment is recommended among the treatments suggested for HCC patients in the very early/early stage. In the last decade, very important results in terms of survival benefits have been obtained with local ablative therapies, also outside the standard indications, thanks to many technical innovations. In particular, important results of ablation as a safe and effective technique have been obtained in the treatment of intermediate- or advanced-stage patients with HCC, and in the treatment of unfavourable tumour locations. Moreover, awareness is growing regarding the necessity of overcoming the rigidity of traditional guidelines in the treatment of HCC due to the complexity of patients with HCC, focusing on Precision Medicine. In this context, it is important to know the standard and non-standard indications of ablation in the treatment of HCC in order to offer the best therapeutic option tailored for each patient. The aim of this study was to analyse the possible clinical applications of ablative therapies for HCC patients, beyond the traditional indications recommended in the most widespread clinical practice guidelines for the management of HCC.
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Affiliation(s)
- Matteo Renzulli
- Radiology Unit, Department of Experimental, Diagnostic and Speciality Medicine, Sant'Orsola Hospital, University of Bologna, Via Albertoni 15, 40138, Bologna, Italy.
| | - Francesco Tovoli
- Unit of Internal Medicine, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Alfredo Clemente
- Radiology and Radiotherapy Unit, Department of Precision Medicine, University of Campania "L. Vanvitelli", Naples, Italy
| | - Anna Maria Ierardi
- Diagnostic and Interventional Radiology Department, ASST Santi Paolo e Carlo, San Paolo Hospital, University of Milan, Milan, Italy
| | - Irene Pettinari
- Radiology Unit, Department of Experimental, Diagnostic and Speciality Medicine, Sant'Orsola Hospital, University of Bologna, Via Albertoni 15, 40138, Bologna, Italy
| | - Giuliano Peta
- Radiology Unit, Department of Experimental, Diagnostic and Speciality Medicine, Sant'Orsola Hospital, University of Bologna, Via Albertoni 15, 40138, Bologna, Italy
| | - Giovanni Marasco
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Davide Festi
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Fabio Piscaglia
- Unit of Internal Medicine, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Salvatore Cappabianca
- Radiology and Radiotherapy Unit, Department of Precision Medicine, University of Campania "L. Vanvitelli", Naples, Italy
| | - Gianpaolo Carrafiello
- Diagnostic and Interventional Radiology Department, ASST Santi Paolo e Carlo, San Paolo Hospital, University of Milan, Milan, Italy
| | - Rita Golfieri
- Radiology Unit, Department of Experimental, Diagnostic and Speciality Medicine, Sant'Orsola Hospital, University of Bologna, Via Albertoni 15, 40138, Bologna, Italy
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El Fayoumie M, Abdelhady M, Gawish A, Hantour U, Abdelkhaleek I, Abdelraheem M, Alsawak A, Alwassief A, Elbahrawy A. Changing Patterns of Hepatocellular Carcinoma after Treatment with Direct Antiviral Agents. Gastrointest Tumors 2020; 7:50-60. [PMID: 32399465 DOI: 10.1159/000505326] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Accepted: 12/07/2019] [Indexed: 12/13/2022] Open
Abstract
Introduction The impact of direct antiviral agents (DAAs) on the development of hepatocellular carcinoma (HCC) is controversial. One important aspect of this controversy is the changing pattern of HCC. Objective In this study, we attempted to assess the changes in the pattern of HCC after treatment with DAAs. Methods A total of 51 HCC patients after DAA treatment and 54 HCC patients without DAA treatment were included. The diagnosis of HCC was based on typical dynamic CT and/or MRI criteria in both groups. Liver status was assessed by means of the fibrosis 4 index (Fib-4), Child-Pugh classification, and model for end-stage liver disease (MELD). HCC infiltrative pattern, portal vein thrombosis (PVT), local and distant metastases, and α-fetoprotein (AFP) level were compared in the 2 groups. The staging of HCC and treatment decisions were made in both groups following the Milan criteria, Barcelona Clinic Liver Cancer staging, tumor-node-metastasis staging, and Cancer of the Liver Italian Program categorization. Results The mean age of the HCC patients after DAA treatment (59.1± 7.4 years) was older than that of the HCC patients without DAA treatment. There was no significant difference between groups regarding sex distribution. The mean Fib-4 score (4.84 ± 3.53) was significantly lower in HCC patients after DAA treatment than in those without DAA treatment. The frequency of the infiltrative HCC pattern, PVT, and regional lymph node metastasis was significantly higher in HCC patients after DAA treatment than in those without DAA treatment (p ≤ 0.05); mean AFP level (5,085.2 ± 11,883.2 ng/mL) was also significantly higher. HCC patients after DAA treatment had significantly advanced stages and limited treatment options (p ≤ 0.05). Conclusion The changing HCC pattern after DAA treatment may suggest the need for new HCC staging and treatment protocols.
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Affiliation(s)
| | | | - Ahmed Gawish
- Department of Internal Medicine, Al-Azhar University, Cairo, Egypt
| | - Usama Hantour
- Department of Tropical Medicine, Al-Azhar University, Cairo, Egypt
| | | | | | - Alaa Alsawak
- Department of Internal Medicine, Al-Azhar University, Cairo, Egypt
| | - Ahmed Alwassief
- Department of Internal Medicine, Al-Azhar University, Cairo, Egypt
| | - Ashraf Elbahrawy
- Department of Internal Medicine, Al-Azhar University, Cairo, Egypt
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Renzulli M, Clemente A, Ierardi AM, Pettinari I, Tovoli F, Brocchi S, Peta G, Cappabianca S, Carrafiello G, Golfieri R. Imaging of Colorectal Liver Metastases: New Developments and Pending Issues. Cancers (Basel) 2020; 12:151. [PMID: 31936319 PMCID: PMC7017094 DOI: 10.3390/cancers12010151] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2019] [Revised: 12/31/2019] [Accepted: 01/06/2020] [Indexed: 02/07/2023] Open
Abstract
Computed tomography (CT), magnetic resonance imaging (MRI), and 18-fluorideoxyglucose positron emission tomography (18FDG-PET) are historically the most accurate imaging techniques for diagnosing liver metastases. Recently, the combination of diffusion-weighted imaging and hepatospecific contrast media, such as gadoxetic acid in MRI, have been demonstrated to have the highest diagnostic accuracy, sensitivity, and specificity for detecting liver metastases. Various recent meta-analyses have confirmed the diagnostic superiority of this combination (diffusion-weighted imaging and gadoxetic acid-enhanced MRI), especially in terms of per lesion sensitivity, as compared with CT and 18FDG-PET, even for smaller lesions (≤1 cm). However, none of the oncological guidelines have suggested the use of MRI as a first-line technique for liver metastasis detection during the staging process of oncological patients. This review analyzes the history of the principal imaging techniques for the diagnosis of liver metastases, in particular of colorectal liver metastases, focusing on the most accurate method (diffusion-weighted imaging combined with gadoxetic acid-enhanced MRI), possible reasons for the lack of its diffusion in the guidelines, and possible future scenarios.
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Affiliation(s)
- Matteo Renzulli
- Radiology Unit, Department of Experimental, Diagnostic and Speciality Medicine, Sant’Orsola Hospital, University of Bologna, 40138 Bologna, Italy; (I.P.); (S.B.); (G.P.); (R.G.)
| | - Alfredo Clemente
- Radiology and Radiotherapy Unit, Department of Precision Medicine, University of Campania “L. Vanvitelli”, 80138 Naples, Italy; (A.C.); (S.C.)
| | - Anna Maria Ierardi
- Diagnostic and Interventional Radiology, ASST Santi Paolo e Carlo, San Paolo Hospital, 20142 Milan, Italy;
| | - Irene Pettinari
- Radiology Unit, Department of Experimental, Diagnostic and Speciality Medicine, Sant’Orsola Hospital, University of Bologna, 40138 Bologna, Italy; (I.P.); (S.B.); (G.P.); (R.G.)
| | - Francesco Tovoli
- Department of Specialised, Experimental and Diagnostic Medicine, Sant’Orsola Hospital, University of Bologna, 40138 Bologna, Italy;
| | - Stefano Brocchi
- Radiology Unit, Department of Experimental, Diagnostic and Speciality Medicine, Sant’Orsola Hospital, University of Bologna, 40138 Bologna, Italy; (I.P.); (S.B.); (G.P.); (R.G.)
| | - Giuliano Peta
- Radiology Unit, Department of Experimental, Diagnostic and Speciality Medicine, Sant’Orsola Hospital, University of Bologna, 40138 Bologna, Italy; (I.P.); (S.B.); (G.P.); (R.G.)
| | - Salvatore Cappabianca
- Radiology and Radiotherapy Unit, Department of Precision Medicine, University of Campania “L. Vanvitelli”, 80138 Naples, Italy; (A.C.); (S.C.)
| | - Gianpaolo Carrafiello
- Unit of Radiology, IRCCS Cà Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy;
| | - Rita Golfieri
- Radiology Unit, Department of Experimental, Diagnostic and Speciality Medicine, Sant’Orsola Hospital, University of Bologna, 40138 Bologna, Italy; (I.P.); (S.B.); (G.P.); (R.G.)
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Li KY, Zhang SM, Shi CX, Tang KL, Huang JZ. Effect of prophylactic transcatheter arterial chemoembolization on hepatocellular carcinoma with microvascular invasion after R0 resection. A case-control study. SAO PAULO MED J 2020; 138:60-63. [PMID: 32321107 PMCID: PMC9673847 DOI: 10.1590/1516-3180.2019.0042.r1.05072019] [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: 05/12/2019] [Accepted: 07/05/2019] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Transcatheter arterial chemoembolization (TACE) is thought to prevent recurrence of hepatocellular carcinoma (HCC), but its efficacy is a matter of controversy. OBJECTIVES We investigated the effect of preventive TACE on the tumor, nodes, metastasis (TNM) classification in cases of stage II HCC (T2N0M0) after R0 resection. DESIGN AND SETTING Case-control study conducted in a tertiary-level public hospital. METHODS We analyzed recurrence rates and mortality rates over time for 250 consecutive cases of HCC in TNM classification cases of stage II HCC (T2N0M0) after R0 resection. These cases were divided into patients who underwent TACE (TACE+) and presented microvascular invasion (MVI+; n = 80); TACE+ but did not present MVI (MIV-; n = 100); MVI+ but did not undergo TACE (TACE-, n = 30); and TACE-/MVI- (n = 40). RESULTS MVI+ patients in the TACE+ group had significantly lower recurrence rates and mortality rates at one, two and three years than those in the TACE- group (all P < 0.05). Among MVI- patients, the TACE+ group did not have significantly lower recurrence rates and mortality rates at one, two and three years than the TACE- group (all P > 0.05). Regardless of whether TACE was performed or not, MVI- patients had significantly lower recurrence rates and mortality rates at two and three years after their procedures than did MVI+ patients (all P < 0.05). CONCLUSION Recurrence rates and mortality rates for MVI+ patients were significantly higher than for MVI- patients, beyond the first year after TACE. Postoperative adjuvant TACE may be beneficial for HCC patients with MVI.
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Affiliation(s)
- Ke-Yue Li
- MD, PhD. Associate Professor of Surgery, Department of Hepatobiliary Surgery, Guizhou Provincial People’s Hospital, Guiyang, Guizhou Province, China.
| | - Shuai-Min Zhang
- MD, MMed. Attending Physician, Department of Hepatobiliary Surgery, Guizhou Provincial People’s Hospital, Guiyang, Guizhou Province, China.
| | - Cheng-Xian Shi
- MD, MMed. Professor of Surgery, Department of Hepatobiliary Surgery, Guizhou Provincial People’s Hospital, Guiyang, Guizhou Province, China.
| | - Ke-Li Tang
- MD, MMed. Professor of Surgery, Department of Hepatobiliary Surgery, Guizhou Provincial People’s Hospital, Guiyang, Guizhou Province, China.
| | - Jian-Zhao Huang
- MD, PhD. Professor of Surgery, Department of Hepatobiliary Surgery, Guizhou Provincial People’s Hospital, Guiyang, Guizhou Province, China.
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El Kassas M, Tawheed A, Eltabbakh M, Kaseb A. Hepatitis C Antiviral Therapy In Patients With Successfully Treated Hepatocellular Carcinoma: Dancing With Wolves. J Hepatocell Carcinoma 2019; 6:183-191. [PMID: 31819865 PMCID: PMC6879003 DOI: 10.2147/jhc.s206668] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Accepted: 10/21/2019] [Indexed: 12/16/2022] Open
Abstract
Hepatitis C virus (HCV) infection is known to be one of the leading causes of hepatocellular carcinoma (HCC) all over the world. Previously, multiple studies have confirmed a decreased rate of HCC occurrence or recurrence in the cases of hepatitis C associated cirrhosis after treatment with interferon, in comparison to the untreated cases, even in the absence of clearance of HCV. Treatment programs with direct-acting antivirals (DAAs) as a new method for HCV treatment and cure in 2014, with higher safety and efficacy, were considered as an important step in the treatment of patients with history of HCC, improving their overall prognosis. Recently, reports coming from various European centers claimed that the risk of HCC increased following DAAs therapy, especially in cases with previous HCC. Moreover, other studies revealed that the recurrence of HCC after DAAs treatment was more aggressive. Even though others were not able to conclude the same results, the role of DAA therapy in recurrence of HCC in patients with previous HCC after sustained virological response (SVR) achievement remains questionable. This review explored the existing literature and discussed opinions on the possibility of increasing recurrence of HCC following DAA therapy, possible mechanisms, predictors of HCC recurrence post DAAs, and whether those patients should be treated or not.
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Affiliation(s)
- Mohamed El Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Ahmed Tawheed
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Mohamed Eltabbakh
- Tropical Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Ahmed Kaseb
- Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
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Dong Y, Wang QM, Li Q, Li LY, Zhang Q, Yao Z, Dai M, Yu J, Wang WP. Preoperative Prediction of Microvascular Invasion of Hepatocellular Carcinoma: Radiomics Algorithm Based on Ultrasound Original Radio Frequency Signals. Front Oncol 2019; 9:1203. [PMID: 31799183 PMCID: PMC6868049 DOI: 10.3389/fonc.2019.01203] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Accepted: 10/23/2019] [Indexed: 01/27/2023] Open
Abstract
Background: To evaluate the accuracy of radiomics algorithm based on original radio frequency (ORF) signals for prospective prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) lesions. Methods: In this prospective study, we enrolled 42 inpatients diagnosed with HCC from January 2018 to December 2018. All HCC lesions were proved by surgical resection and histopathology results, including 21 lesions with MVI. Ultrasound ORF data and grayscale ultrasound images of HCC lesions were collected before operation for further radiomics analysis. Three ultrasound feature maps were calculated using signal analysis and processing (SAP) technology in first feature extraction. The diagnostic accuracy of model based on ORF signals was compared with the model based on grayscale ultrasound images. Results: A total of 1,050 radiomics features were extracted from ORF signals of each HCC lesion. The performance of MVI prediction model based on ORF was better than those based on grayscale ultrasound images. The best area under curve, accuracy, sensitivity, and specificity of ultrasound radiomics in prediction of MVI were 95.01, 92.86, 85.71, and 100%, respectively. Conclusions: Radiomics algorithm based on ultrasound ORF data combined with SAP technology can effectively predict MVI, which has potential clinical application value for non-invasively preoperative prediction of MVI in HCC patients.
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Affiliation(s)
- Yi Dong
- Zhongshan Hospital, Fudan University, Shanghai, China
| | - Qing-Min Wang
- Department of Electronic Engineering, Fudan University, Shanghai, China
| | - Qian Li
- Harvard Medical School, Massachusetts General Hospital, Boston, MA, United States
| | - Le-Yin Li
- Department of Electronic Engineering, Fudan University, Shanghai, China
| | - Qi Zhang
- Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhao Yao
- Department of Electronic Engineering, Fudan University, Shanghai, China
| | - Meng Dai
- Department of Electronic Engineering, Fudan University, Shanghai, China
| | - Jinhua Yu
- Department of Electronic Engineering, Fudan University, Shanghai, China
| | - Wen-Ping Wang
- Zhongshan Hospital, Fudan University, Shanghai, China
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Ninio L, Nissani A, Meirson T, Domovitz T, Genna A, Twafra S, Srikanth KD, Dabour R, Avraham E, Davidovich A, Gil-Henn H, Gal-Tanamy M. Hepatitis C Virus Enhances the Invasiveness of Hepatocellular Carcinoma via EGFR-Mediated Invadopodia Formation and Activation. Cells 2019; 8:cells8111395. [PMID: 31694343 PMCID: PMC6912298 DOI: 10.3390/cells8111395] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2019] [Revised: 10/30/2019] [Accepted: 11/01/2019] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) represents the fifth most common cancer worldwide and the third cause of cancer-related mortality. Hepatitis C virus (HCV) is the leading cause of chronic hepatitis, which often results in liver fibrosis, cirrhosis, and eventually HCC. HCV is the most common risk factor for HCC in western countries and leads to a more aggressive and invasive disease with poorer patient survival rates. However, the mechanism by which the virus induces the metastatic spread of HCC tumor cells through the regulation of invadopodia, the key features of invasive cancer, is still unknown. Here, the integration of transcriptome with functional kinome screen revealed that HCV infection induced invasion and invadopodia-related gene expression combined with activation of host cell tyrosine kinases, leading to invadopodia formation and maturation and consequent cell invasiveness in vitro and in vivo. The promotion of invadopodia following HCV infection was mediated by the sustained stimulation of epidermal growth factor receptor (EGFR) via the viral NS3/4A protease that inactivates the T-cell protein tyrosine phosphatase (TC-PTP), which inhibits EGFR signaling. Characterization of an invadopodia-associated gene signature in HCV-mediated HCC tumors correlated with the invasiveness of HCC and poor patient prognosis. These findings might lead to new prognostic and therapeutic strategies for virus-mediated invasive cancer.
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Affiliation(s)
- Liat Ninio
- Molecular Virology Laboratory, Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel; (L.N.); (A.N.); (T.D.); (R.D.); (E.A.); (A.D.)
- Cell Migration and Invasion Laboratory, Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel; (T.M.); (A.G.); (S.T.); (K.D.S.)
| | - Abraham Nissani
- Molecular Virology Laboratory, Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel; (L.N.); (A.N.); (T.D.); (R.D.); (E.A.); (A.D.)
| | - Tomer Meirson
- Cell Migration and Invasion Laboratory, Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel; (T.M.); (A.G.); (S.T.); (K.D.S.)
- Drug Discovery Laboratory, Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel
| | - Tom Domovitz
- Molecular Virology Laboratory, Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel; (L.N.); (A.N.); (T.D.); (R.D.); (E.A.); (A.D.)
| | - Alessandro Genna
- Cell Migration and Invasion Laboratory, Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel; (T.M.); (A.G.); (S.T.); (K.D.S.)
| | - Shams Twafra
- Cell Migration and Invasion Laboratory, Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel; (T.M.); (A.G.); (S.T.); (K.D.S.)
| | - Kolluru D. Srikanth
- Cell Migration and Invasion Laboratory, Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel; (T.M.); (A.G.); (S.T.); (K.D.S.)
| | - Roba Dabour
- Molecular Virology Laboratory, Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel; (L.N.); (A.N.); (T.D.); (R.D.); (E.A.); (A.D.)
| | - Erez Avraham
- Molecular Virology Laboratory, Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel; (L.N.); (A.N.); (T.D.); (R.D.); (E.A.); (A.D.)
| | - Ateret Davidovich
- Molecular Virology Laboratory, Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel; (L.N.); (A.N.); (T.D.); (R.D.); (E.A.); (A.D.)
| | - Hava Gil-Henn
- Cell Migration and Invasion Laboratory, Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel; (T.M.); (A.G.); (S.T.); (K.D.S.)
- Correspondence: (H.G.-H.); (M.G.-T.)
| | - Meital Gal-Tanamy
- Molecular Virology Laboratory, Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel; (L.N.); (A.N.); (T.D.); (R.D.); (E.A.); (A.D.)
- Correspondence: (H.G.-H.); (M.G.-T.)
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Grzegorzewska AE. Genetic Polymorphisms within Interferon-λ Region and Interferon-λ3 in the Human Pathophysiology: Their Contribution to Outcome, Treatment, and Prevention of Infections with Hepatotropic Viruses. Curr Med Chem 2019; 26:4832-4851. [DOI: 10.2174/0929867325666180719121142] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2017] [Revised: 03/21/2018] [Accepted: 07/09/2018] [Indexed: 12/16/2022]
Abstract
:
Genetic polymorphisms within the interferon λ (IFN-λ) chromosomal region,
mainly rs12979860 of IFN-λ4 gene (IFNL4), are known as associated with spontaneous hepatitis
C virus (HCV) resolution and sustained viral response to therapy with pegylated interferon-
α and ribavirin. Strong linkage disequilibrium of IFNL4 rs12979860 with IFNL4
rs368234815, which is casually associated with HCV spontaneous and therapeutical eradication,
at least partially explains favorable HCV outcomes attributed to major homozygosity in
rs12979860. Effects of IFN-based antiviral treatment are associated with pretreatment expression
of the IFN-λ1 receptor, expression of hepatic IFN-stimulated genes, production of IFN-
λ4, and preactivation of the JAK-STAT signaling. Nowadays direct-acting antivirals (DAAs)
became a potent tool in the treatment of hepatitis C, but IFN-λs are still under investigation as
potential antivirals and might be an option in HCV infection (DAA resistance, recurrent viremia,
adverse effects).
:
Patients with altered immunocompetence are especially prone to infections. In uremic subjects,
polymorphisms within the IFN-λ chromosomal region associate with spontaneous HCV
clearance, similarly like in the non-uremic population. Circulating IFN-λ3 shows a positive
correlation with plasma titers of antibodies to surface antigen of hepatitis B virus (anti-HBs),
which are crucial for protection against hepatitis B virus. More efficient anti-HBs production
in the presence of higher IFN-λ3 levels might occur due to IFN-λ3-induced regulation of indoleamine
2,3-dioxygenase (IDO) expression. IFN-stimulated response element is a part of
IDO gene promoter. It is worth further investigation whether IDO gene, circulating IDO, genetic
polymorphisms within the IFN-λ region, and circulating IFN-λ3 act in concordance in
immunological response to hepatotropic viruses.
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Affiliation(s)
- Alicja E. Grzegorzewska
- Chair and Department of Nephrology, Transplantology and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland
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Lymphovascular invasion on explant is associated with presenting tumor characteristics and not direct acting antiviral utilization in hepatitis C candidates undergoing liver transplantation. Clin Exp Hepatol 2019; 5:279-284. [PMID: 31893238 PMCID: PMC6935850 DOI: 10.5114/ceh.2019.88105] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Accepted: 06/16/2019] [Indexed: 12/11/2022] Open
Abstract
Aim of the study Utilization of direct acting antiviral (DAA) therapy in candidates with well-compensated hepatitis C virus (HCV) cirrhosis and hepatocellular carcinoma (HCC) accruing end stage liver disease (MELD) exception points is highly variable among transplant centers based on center location, local organ procurement dynamics, HCV(+) organ availability, and patient preference. The association between DAA utilization prior to transplant and incidence of lymphovascular invasion on explant is unknown. Material and methods Retrospective evaluation from 2013-2017 of patients on a liver transplant (LT) waitlist with HCV-related cirrhosis, MELD-Na < 15, and HCC (within T2/Milan criteria). The cohort was divided into the pre-LT DAA treated group and untreated group with clinical/viral demographics collected. Tumor presenting characteristics, locoregional treatments, wait time to LT, dropout rates and explant pathology were compared. Results DAAs were used in 44 patients prior to LT (SVR12 of 37/44 [84%]) and 19 left untreated with LT performed in 81% (51/63) of the waitlisted cohort. No significant differences were found between groups with regards to clinical/viral demographics, local-regional therapy (LRT) sessions, or frequency of lymphovascular invasion on explant. The untreated cohort had a higher rate of dropout (6.3% vs. 3.2%) (p = 0.041). On subgroup analysis of 51 subjects undergoing LT, AFP > 250 ng/ml (p = 0.003) and multifocal HCC (> 1 lesion) (p = 0.006) were associated with lymphovascular invasion on explant while DAA therapy was not (p = 0.578). Conclusions DAA therapy for waitlist active HCV candidates accruing MELD exception points has no deleterious effects on bridging LRT, nor is it associated with increased frequency of lymphovascular invasion on explant. The latter appears driven by tumor related characteristics (AFP and number of lesions) irrespective of DAA utilization prior to LT.
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Hernáez-Alsina T, Caballol-Oliva B, Díaz-González Á, Guedes-Leal C, Reig M. Risk of recurrence of hepatocellular carcinoma in patients treated with interferon-free antivirals. GASTROENTEROLOGIA Y HEPATOLOGIA 2019; 42:502-511. [PMID: 31472990 DOI: 10.1016/j.gastrohep.2019.05.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Revised: 05/01/2019] [Accepted: 05/07/2019] [Indexed: 12/18/2022]
Abstract
Eradication of the hepatitis C virus (HCV) with interferon-free therapies (DAAs) has modified the course of the disease, as the rate of patients with compensated cirrhosis who achieve a sustained virological response exceeds 95%. However, the impact on development of hepatocellular carcinoma (HCC) is currently in dispute. This argument could be divided into different key points: the impact of DAA on rate of HCC recurrence, the temporal link between starting DAAs and HCC recurrence, and finally, the aggressive pattern of HCC. Therefore, the aim of this review is to analyse the available results in this population of patients from a clinical perspective where the risks and benefits of HCV eradication with DAA therapies are evaluated in patients with complete response of HCC.
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Affiliation(s)
- Tania Hernáez-Alsina
- Servicio de Aparato Digestivo, Hospital San Pedro, Logroño, La Rioja, España; Grupo BCLC, Unidad de Oncología Hepática, Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Universidad de Barcelona, Barcelona, España
| | - Berta Caballol-Oliva
- Grupo BCLC, Unidad de Oncología Hepática, Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Universidad de Barcelona, Barcelona, España
| | - Álvaro Díaz-González
- Grupo BCLC, Unidad de Oncología Hepática, Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Universidad de Barcelona, Barcelona, España
| | - Cassia Guedes-Leal
- Grupo BCLC, Unidad de Oncología Hepática, Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Universidad de Barcelona, Barcelona, España
| | - María Reig
- Grupo BCLC, Unidad de Oncología Hepática, Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Universidad de Barcelona, Barcelona, España.
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Rutledge SM, Zheng H, Li DK, Chung RT. No evidence for higher rates of hepatocellular carcinoma after direct-acting antiviral treatment: a meta-analysis. ACTA ACUST UNITED AC 2019; 5. [PMID: 31453368 PMCID: PMC6709867 DOI: 10.20517/2394-5079.2019.19] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Aim: Hepatitis C virus (HCV) is the leading cause of hepatocellular carcinoma (HCC) in the United States. Achieving sustained viral response with interferon (IFN) treatment reduces the risk from 3%-5% to 0.5%-1% annually. Several studies reported unexpectedly high rates of HCC after treatment with direct-acting antivirals (DAAs). The aim of our study was to compare HCC rates in DAA-, IFN-treated and untreated populations. Methods: A literature search was conducted using ScienceDirect, Ovid®, Web of Science and MEDLINE through January 2019. Studies were included if they measured rates of de novo or recurrent HCC (following curative treatment) in HCV-infected persons. We included 138 studies (n = 177,512). Simple pooling of data and meta-analysis were performed, using the random effects method. Results: Mean age was higher in the DAA-treated vs. IFN-treated group (58.4 years vs. 52.6 years; P = 0.0073), as were diabetes prevalence (34.5% vs. 11.7%; P ≤ 0.001) and incident cirrhosis (47.8% vs. 34.2%, P = 0.0017). The incidence rate of de novo HCC was 2.01/100 person-years (py) (95%CI: 1.38, 2.67) in the DAA group and 1.45/100py (95%CI: 0.98, 1.94) in the IFN-treated group. HCC recurred at 16.76/100py (95%CI: 10.75, 22.91) in the DAA-treated group vs. 20.04/100py (95%CI: 2.58, 45.21) after IFN. After adjusting for factors such as age and cirrhosis, the hazard ratio was 0.58 (95%CI: 0.20, 1.07) for HCC occurrence and 0.59 (95%CI: 0.24, 1.03) for HCC recurrence after DAA treatment compared to IFN-based treatment. Conclusion: We did not find evidence for increased rates of HCC in DAA-treated compared with IFN-treated patients. Compared to those treated with IFN, older patients with additional risk factors for HCC were treated with DAAs. This imbalance appears to explain the higher numerical incidence of HCC among DAA-treated patients.
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Affiliation(s)
- Stephanie M Rutledge
- Department of Medicine, Massachusetts General Hospital, Gastroenterology Unit/Warren 10, Boston, MA02114, USA.,Liver Center, Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
| | - Hui Zheng
- Liver Center, Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
| | - Darrick K Li
- Department of Medicine, Massachusetts General Hospital, Gastroenterology Unit/Warren 10, Boston, MA02114, USA.,Liver Center, Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
| | - Raymond T Chung
- Department of Medicine, Massachusetts General Hospital, Gastroenterology Unit/Warren 10, Boston, MA02114, USA.,Liver Center, Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
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Guo D, Gu D, Wang H, Wei J, Wang Z, Hao X, Ji Q, Cao S, Song Z, Jiang J, Shen Z, Tian J, Zheng H. Radiomics analysis enables recurrence prediction for hepatocellular carcinoma after liver transplantation. Eur J Radiol 2019; 117:33-40. [PMID: 31307650 DOI: 10.1016/j.ejrad.2019.05.010] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Revised: 05/05/2019] [Accepted: 05/08/2019] [Indexed: 02/07/2023]
Abstract
OBJECTIVES To assess whether radiomics signature can identify aggressive behavior and predict recurrence of hepatocellular carcinoma (HCC) after liver transplantation. METHODS Our study consisted of a training dataset (n = 93) and a validation dataset (40) with clinically confirmed HCC after liver transplantation from October 2011 to December 2016. Radiomics features were extracted by delineating regions-of-interest (ROIs) around the lesion in four phases of CT images. A radiomics signature was generated using the least absolute shrinkage and selection operator (LASSO) Cox regression model. The association between radiomics signature and recurrence-free survival (RFS) was assessed. Preoperative clinical characteristics potentially associated with RFS were evaluated to develop a clinical model. A combined model incorporating clinical risk factors and radiomics signature was built. RESULTS The stable radiomics features associated with the recurrence of HCC were simply found in arterial phase and portal phase. The prediction model based on the radiomics features extracted from the arterial phase showed better prediction performance than the portal vein phase or the fusion signature combining both of arterial and portal vein phase. A radiomics nomogram based on combined model consisting of the radiomics signature and clinical risk factors showed good predictive performance for RFS with a C-index of 0.785 (95% confidence interval [CI]: 0.674-0.895) in the training dataset and 0.789 (95% CI: 0.620-0.957) in the validation dataset. The calibration curves showed agreement in both training (p = 0.121) and validation cohorts (p = 0.164). CONCLUSIONS Radiomics signature extracted from CT images may be a potential imaging biomarker for liver cancer invasion and enable accurate prediction of HCC recurrence after liver transplantation.
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Affiliation(s)
- Donghui Guo
- First Central Clinical College of Tianjin Medical University, Tianjin 300192, PR China
| | - Dongsheng Gu
- CAS Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, PR China
| | - Honghai Wang
- Oriental Organ Transplant Center of Tianjin First Central Hospital, Tianjin 300192, PR China
| | - Jingwei Wei
- CAS Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, PR China
| | - Zhenglu Wang
- Oriental Organ Transplant Center of Tianjin First Central Hospital, Tianjin 300192, PR China
| | - Xiaohan Hao
- CAS Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, PR China
| | - Qian Ji
- Oriental Organ Transplant Center of Tianjin First Central Hospital, Tianjin 300192, PR China
| | - Shunqi Cao
- First Central Clinical College of Tianjin Medical University, Tianjin 300192, PR China
| | - Zhuolun Song
- Oriental Organ Transplant Center of Tianjin First Central Hospital, Tianjin 300192, PR China
| | - Jiabing Jiang
- First Central Clinical College of Tianjin Medical University, Tianjin 300192, PR China
| | - Zhongyang Shen
- Oriental Organ Transplant Center of Tianjin First Central Hospital, Tianjin 300192, PR China
| | - Jie Tian
- CAS Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, PR China.
| | - Hong Zheng
- Oriental Organ Transplant Center of Tianjin First Central Hospital, Tianjin 300192, PR China.
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Galati G, Muley M, Viganò M, Iavarone M, Vitale A, Dell'Unto C, Lai Q, Cabibbo G, Sacco R, Villa E, Trevisani F. Occurrence of hepatocellular carcinoma after direct-acting antiviral therapy for hepatitis C virus infection: literature review and risk analysis. Expert Opin Drug Saf 2019; 18:603-610. [PMID: 31067134 DOI: 10.1080/14740338.2019.1617272] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2019] [Accepted: 05/07/2019] [Indexed: 12/26/2022]
Abstract
INTRODUCTION Concerns were raised about a high occurrence of hepatocellular carcinoma (HCC) after successful treatment of chronic hepatitis C (CHC) by direct-acting antivirals (DAAs). AREAS COVERED The authors summarize the clinical studies reporting the occurrence rate and risk factors of HCC after DAAs in CHC. EXPERT OPINION The recent introduction of all-oral DAAs has substantially changed the scenario of CHC, achieving a sustained virological response (SVR) in >90% of cases. Earlier concerns raised about an increasing incidence of HCC post-DAAs were flawed by large heterogeneity of patients, the limited number of well-designed prospective studies (only nine, up to date) and the inclusion of a large number of patients with advanced liver disease, previously excluded from interferon-based studies. Current data on DAAs have shown a lower risk of HCC development; however, they were unable to identify patients at greater risk for HCC occurrence after SVR. Surveillance strategy, likely lifelong, is mandatory in these patients according to general expert opinion.
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Affiliation(s)
- Giovanni Galati
- a Internal Medicine and Hepatology Unit , University Campus Bio-Medico , Rome , Italy
| | - Moises Muley
- a Internal Medicine and Hepatology Unit , University Campus Bio-Medico , Rome , Italy
| | - Mauro Viganò
- b Hepatology Unit, Ospedale San Giuseppe , University of Milan , Milan , Italy
| | - Massimo Iavarone
- c C.R.C. "A.M. & A. Migliavacca Center for Liver Disease" and Division of Gastroenterology and Hepatology , University of Milan and Fondazione IRCCS Ca' Granda Maggiore Hospital , Milan , Italy
| | - Alessandro Vitale
- d Department of Surgery, Oncology and Gastroenterology , University of Padua , Padua , Italy
| | - Chiara Dell'Unto
- a Internal Medicine and Hepatology Unit , University Campus Bio-Medico , Rome , Italy
| | - Quirino Lai
- e Hepatobiliopancreatic Surgery and Liver Transplantation Unit , Sapienza University of Rome , Rome , Italy
| | - Giuseppe Cabibbo
- f Gastroenterology and Hepatology Unit , PROMISE University of Palermo , Palermo , Italy
| | - Rodolfo Sacco
- g Gastroenterology and Digestive Endoscopy , Foggia University Hospital , Foggia , Italy
| | - Erica Villa
- h Gastroenterology Unit , University of Modena & Reggio Emilia , Modena , Italy
| | - Franco Trevisani
- i Dipartimento di Scienze Mediche e Chirurgiche Alma Mater Studiorum , Università di Bologna , Bologna , Italy
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Malloy PC. Combination Therapy in Intermediate-Stage Hepatocellular Carcinoma: Do We Need to Know about Microvascular Invasion? Radiology 2019; 292:248-249. [PMID: 31136261 DOI: 10.1148/radiol.2019190921] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Affiliation(s)
- Patrick C Malloy
- From the Department of Radiology, New York University School of Medicine, New York, NY
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Renzulli M, Brocchi S, Pettinari I, Biselli M, Clemente A, Corcioni B, Cappabianca S, Gaudiano C, Golfieri R. New MRI series for kidney evaluation: Saving time and money. Br J Radiol 2019; 92:20190260. [PMID: 31046410 DOI: 10.1259/bjr.20190260] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
OBJECTIVES This study investigates the diagnostic performance of a new T1 imaging series, generated by the digital subtraction of the opposed phase from in phase T 1 weighted images, in MRI for renal angiomyolipoma (AML) evaluation. METHODS This retrospective study involved 96 patients, 63 (65.6%) with at least one renal AML and 33 (34.4%) healthy patients. Two radiologists having different experience retrospectively reviewed two MR imaging series, starting with in and out-phase T 1 weighted images and then the new subtracted T1 images, in which AML appeared white on black background. The presence, number, location, and dimensions of the AMLs, and reading time were collected separately for the two kidneys. Statistical analysis was carried out using the appropriate tests. RESULTS The number of lesions identified and the evaluation of lesion dimension did not statistically differ between the different MR imaging series evaluated, without interobserver variability. Both percentage agreement of the total number of observations and the κ coefficient showed very good agreement between the radiologists. The median time for the diagnosis was statistically lower when using the subtracted T1 imaging series for both observers with a median gain from 6.5 to 15 s per identified lesion, resulting in a total time-saving of more than half (52.9%), in both patients with and without AMLs, and in patients with a single or with more than one AML (p < 0.001). CONCLUSIONS The new subtracted T1 imaging series proved to be reliable in identifying fat-containing renal lesions, by both expert and non-expert radiologists, resulting in a saving of both time and money. Moreover, this new subtracted T1 imaging series could be an effective tool in non-dedicated kidney examinations in which a faster reading is advisable. ADVANCES IN KNOWLEDGE The opportunity of using a single set of MRI images in kidney evaluation for identifying fat-containing lesions, considerably reducing reading time, resulting in cost-effectiveness.
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Affiliation(s)
- Matteo Renzulli
- 1 Department of Diagnostic Medicine and Prevention Radiology Unit, Sant'Orsola Hospital, University of Bologna, Via Albertoni , Bologna , Italy
| | - Stefano Brocchi
- 1 Department of Diagnostic Medicine and Prevention Radiology Unit, Sant'Orsola Hospital, University of Bologna, Via Albertoni , Bologna , Italy
| | - Irene Pettinari
- 1 Department of Diagnostic Medicine and Prevention Radiology Unit, Sant'Orsola Hospital, University of Bologna, Via Albertoni , Bologna , Italy
| | - Maurizio Biselli
- 2 Department of Medical and Surgical Sciences, Sant'Orsola Hospital, University of Bologna, Via Albertoni , Bologna , Italy
| | - Alfredo Clemente
- 3 Department of Precision Medicine Radiology and Radiotherapy Unit, University of Campania "L. Vanvitelli", Piazza Miraglia , Naples , Italy
| | - Beniamino Corcioni
- 1 Department of Diagnostic Medicine and Prevention Radiology Unit, Sant'Orsola Hospital, University of Bologna, Via Albertoni , Bologna , Italy
| | - Salvatore Cappabianca
- 3 Department of Precision Medicine Radiology and Radiotherapy Unit, University of Campania "L. Vanvitelli", Piazza Miraglia , Naples , Italy
| | - Caterina Gaudiano
- 1 Department of Diagnostic Medicine and Prevention Radiology Unit, Sant'Orsola Hospital, University of Bologna, Via Albertoni , Bologna , Italy
| | - Rita Golfieri
- 1 Department of Diagnostic Medicine and Prevention Radiology Unit, Sant'Orsola Hospital, University of Bologna, Via Albertoni , Bologna , Italy
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El Kassas M, Elbaz T, Salaheldin M, Abdelsalam L, Kaseb A, Esmat G. Impact of treating chronic hepatitis C infection with direct-acting antivirals on the risk of hepatocellular carcinoma: The debate continues - A mini-review. J Adv Res 2019; 17:43-48. [PMID: 31193326 PMCID: PMC6526204 DOI: 10.1016/j.jare.2019.03.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Revised: 01/26/2019] [Accepted: 03/03/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus clearance is expected in more than 95% of patients treated with direct-acting antivirals (DAAs). However, an extensive debate about the impact of DAAs on the development of hepatocellular carcinoma (HCC) is currently ongoing. This review aimed to explore currently available evidence about the relationship between DAAs and HCC development. The American studies and some European studies clearly showed no relation, while the Japanese and Egyptian studies and the other European studies showed an increased risk of developing HCC after DAA exposure. These conflicting results may be due to geographical and ethnic variations and differences in the design and inclusion criteria among the studies. After reviewing the data from these different studies, it seems that some patients are at increased risk of developing HCC after DAA exposure. Identifying those at increased risk is very important for the management of HCC in light of the potentially major consequences of HCC for the patients' quality of life and the subsequent major burden imposed on healthcare resources.
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Affiliation(s)
- Mohamed El Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Tamer Elbaz
- Endemic Medicine and Hepatogastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed Salaheldin
- Tropical Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Lobna Abdelsalam
- Genome Unit, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed Kaseb
- Department of Gastrointestinal Medical Oncology, The University of Texas, M.D. Anderson Cancer Center, Texas, USA
| | - Gamal Esmat
- Endemic Medicine and Hepatogastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
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Sanduzzi-Zamparelli M, Boix L, Leal C, Reig M. Hepatocellular Carcinoma Recurrence in HCV Patients Treated with Direct Antiviral Agents. Viruses 2019; 11:E406. [PMID: 31052463 PMCID: PMC6563506 DOI: 10.3390/v11050406] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2019] [Revised: 04/23/2019] [Accepted: 04/25/2019] [Indexed: 02/06/2023] Open
Abstract
The risk of hepatocellular carcinoma recurrence is universal regardless of the treatment modality applied, and secondary prevention is still an unmet issue even though the elimination of hepatitis C (HCV) with direct antiviral agents (DAAs) was expected to be one of the new options. Unfortunately, the impact of DAAs on hepatocellular carcinoma (HCC) development (de novo and recurrence) is still controversial. Since the first publication on the subject in 2016, almost all groups worldwide have carried out research in this field with hundreds of publications now available. This revision is focused on the impact of DAAs on HCC recurrence and aims to discuss the potential underlying mechanisms and host factors pointing out the time association phenomenon between DAA treatment and HCC recurrence. Moreover, we comment on the methodological issues that could affect the different interpretations of the published results. In conclusion, this is an area of research with potential in the understanding of the impact of factors not previously considered, and may also help change hepatocarcinogenesis tenets, such as the belief that the elimination of HCV should be used as a second prevention treatment.
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Affiliation(s)
- Marco Sanduzzi-Zamparelli
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clínic Barcelona, IDIBAPS, University of Barcelona, 08036 Barcelona, Spain.
| | - Loreto Boix
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clínic Barcelona, IDIBAPS, University of Barcelona, 08036 Barcelona, Spain.
- Centro de Investigación Médica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain.
| | - Cassia Leal
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clínic Barcelona, IDIBAPS, University of Barcelona, 08036 Barcelona, Spain.
| | - María Reig
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clínic Barcelona, IDIBAPS, University of Barcelona, 08036 Barcelona, Spain.
- Centro de Investigación Médica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain.
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Abstract
As opposed to most solid cancers, hepatocellular carcinoma (HCC) does not necessarily require histological confirmation. Noninvasive diagnosis is possible and relies on imaging. In cirrhotic patients, the diagnosis can be obtained in tumors displaying typical features that include non-rim arterial phase hyperenhancement followed by washout during the portal venous and/or delayed phases on CT or MR imaging. This pattern is very specific and, as such, has been endorsed by both Western and Asian diagnostic guidelines and systems. However, its sensitivity is not very high, especially for small lesions. Numerous ancillary features favoring the diagnosis of HCC may be depicted, including appearance after injection of hepatobiliary MR imaging contrast agents. These features increase confidence in diagnosis, but cannot be used as substitutes to liver biopsy. Aside from its diagnostic purpose, imaging also helps to assess tumor biology and patient outcome, by identifying features of local invasiveness. The purpose of this review article is to offer an overview of the role of imaging for the diagnosis and prognostication of HCC.
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Preda CM, Baicus C, Sandra I, Oproiu A, Manuc T, Constantinescu I, Gavrila D, Diculescu M, Dumitru R, Vasilescu C, Tieranu C, Istratescu D, Voiosu T, Manuc M. Recurrence rate of hepatocellular carcinoma in patients with treated hepatocellular carcinoma and hepatitis C virus-associated cirrhosis after ombitasvir/paritaprevir/ritonavir+dasabuvir+ribavirin therapy. United European Gastroenterol J 2019; 7:699-708. [PMID: 31210948 DOI: 10.1177/2050640619841254] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2018] [Accepted: 03/08/2019] [Indexed: 12/29/2022] Open
Abstract
Introduction Recent studies have suggested a higher recurrence rate of hepatocellular carcinoma (HCC) in patients with a history of HCC and hepatitis C virus (HCV)-associated cirrhosis treated with direct-acting antiviral (DAA) agents. Material and methods We conducted a prospective analysis of 24 patients with HCV-associated cirrhosis and treated HCC who received ombitasvir/paritaprevir/ritonavir+dasabuvir+ribavirin for 12 weeks. Prior therapies for HCC included resection (9/24 patients), radiofrequency ablation (RFA) (7/24) and trans-arterial chemoembolization (TACE) (8/24). All patients were eligible for treatment if they had no HCC recurrence 6 months after their last procedure. A control group was defined. All patients were followed every 6 months, with dynamic computed tomography and/or magnetic resonance imaging. Results The sustained virological response rate per protocol was 21/24 (87.5%). The study group included 14 (59%) males, median age 64 years (51-77), 50% with associated non-alcoholic steatohepatitis and 24% with Child-Pugh A6 points. HCC recurrence rate/100 patient-years was lower in the DAA-HCC group versus control: 5.5 versus 24.6% patient-years for the resection+RFA group (p = 0.044), respectively, and 18.6 versus 72.7% patient-years for TACE group (p = 0.002). Survival without recurrence was higher in the resection+RFA group (45 compared to 18 months (p < 0.001)) and also in the TACE group (44 compared to 11.5 months (p = 0.002)). Conclusions DAA therapy significantly reduced the recurrence rate of HCC and improved survival without recurrence in patients with treated HCV-associated HCC.
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Affiliation(s)
- Carmen M Preda
- Gastroenterology and Hepatology Department, Clinic Fundeni Institute, Bucharest, Romania
| | - Cristian Baicus
- Internal Medicine Department, Colentina Hospital, Bucharest, Romania
| | - Irina Sandra
- Gastroenterology and Hepatology Department, Clinic Fundeni Institute, Bucharest, Romania
| | - Alexandru Oproiu
- Gastroenterology and Hepatology Department, Clinic Fundeni Institute, Bucharest, Romania
| | - Teodora Manuc
- Gastroenterology and Hepatology Department, Clinic Fundeni Institute, Bucharest, Romania
| | - Ileana Constantinescu
- Gastroenterology and Hepatology Department, Clinic Fundeni Institute, Bucharest, Romania
| | - Daniel Gavrila
- Surgery Department, Clinic Fundeni Institute, Bucharest, Romania
| | - Mircea Diculescu
- Gastroenterology and Hepatology Department, Clinic Fundeni Institute, Bucharest, Romania
| | - Radu Dumitru
- Radiology Department, Clinic Fundeni Institute, Bucharest, Romania
| | | | - Cristian Tieranu
- Gastroenterology and Hepatology Department, Elias Emergency Hospital, Bucharest, Romania
| | - Doina Istratescu
- Gastroenterology and Hepatology Department, Clinic Fundeni Institute, Bucharest, Romania
| | - Theodor Voiosu
- Internal Medicine Department, Colentina Hospital, Bucharest, Romania
| | - Mircea Manuc
- Gastroenterology and Hepatology Department, Clinic Fundeni Institute, Bucharest, Romania
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