{"paper_id":"1d785723-7756-4875-839d-8facee52db88","body_text":"Vascular invasion in hepatocellular carcinoma developed after direct-acting antiviral therapy: CT and MRI assessment | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Vascular invasion in hepatocellular carcinoma developed after direct-acting antiviral therapy: CT and MRI assessment Heba Said Ellaban, Sameh Abdel Mawgoud Afify, Rasha Abdelhafiz Aly This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6280217/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 11 Feb, 2026 Read the published version in Egyptian Journal of Radiology and Nuclear Medicine → Version 1 posted You are reading this latest preprint version Abstract Background The effects of direct-acting antivirals (DAAs) on vascular invasion after curative hepatocellular carcinoma (HCC) treatment remain controversial. Thus, this work aimed to assess the vascular invasion of HCC after DAAs treatment via imaging by computerized tomography (CT) and magnetic resonance imaging (MRI). Methods This case-control study was carried out on 102 cases, 18 years or older, both sexes, with HCV-related HCC. Patients were divided into equal groups; Patients treated with DAAs (group I), and patients who were not treated with DAAs (group II). Group I received two different regimes of DAA dose, 12 weeks of sofosbuvir (400 mg)/velpatasvir (100 mg) once a day and 12 weeks of sofosubuvir 400g/daclatasvir 60g once a day. Results Microvascular invasion occurred in 16 (31.37%) patients in group I, and in 5 (9.8%) patients in group II. Portal invasion occurred in 23 (45.1%) patients in group I, and in 9 (17.65%) patients in group II. size of lesions, no enhancement, nodal and pulmonary deposits were significantly increase in group I than group II (P < 0.05). Site of lesions was significantly different between both groups. Comparing group, I to group II, heterogeneous enhancement was significantly decreased (P < 0.001). Focal lesions, peripheral and homogenous enhancements, and bone deposits were insignificantly different between both groups. Conclusions DAAs had a potential impact on the characteristics and distribution of HCC lesions. DAAs were associated with an increase in incidence of microvascular invasion, portal vein invasion, lesion size, and the presence of nodal and pulmonary deposits. CT DAAs HCC MRI Vascular Invasion Figures Figure 1 Figure 2 Figure 3 Figure 4 BACKGROUND Hepatocellular carcinoma (HCC) is the 6th most frequent malignancy and the 3rd leading reason of cancer-related mortality worldwide [ 1 ] . HCC is a substantial public health concern in Egypt, accounting for 33.63% of all cancers in men and 13.54% in females [ 2 ] . Conversely, hepatitis C virus infection (HCV) is well recognized as a prominent etiology of chronic liver disease in several countries, including Egypt, Europe, and the United States [ 3 , 4 ] . Annually, the risk of HCC development is between 2% and 8% in patients with HCV-associated liver cirrhosis [ 5 ] . In recent years, the introduction of new, effective IFN-free direct-acting antiviral (DAA), has significantly advanced the treatment of hepatitis C virus (HCV). These advancements have resulted in over 90% of treated patients achieving a sustained virological response (SVR), marking a significant improvement even among populations previously thought to be challenging to treat [ 6 , 7 ] . Even in advanced cirrhosis, DAAs improved the treatment of chronic HCV-associated SVR with minimal contraindications and a low incidence of side effects. Nonetheless, chronic liver disease continues to increase the risk of HCC in individuals with and without a prior HCC history [ 8 ] . Therefore, it is anticipated that the administration of DAAs would substantially decrease the HCC incidence and recurrence in cases with advanced fibrosis. HCV-associated cirrhosis patients may benefit from DAAs, which reported to reduce HCC risk and improve portal hypertension and fibrosis [ 9 ] . In HCC, vascular invasion is indicative of poor overall survival and recurrence. Specifically, microvascular invasion (MVI) following curative treatment is a substantial risk factor for early recurrence of HCC [ 10 ] . Prior research endeavored to construct prediction algorithms for MVI by using the radiomics method or a hybrid strategy including both radiologic characteristics and radiomics extracted from magnetic resonance imaging (MRI) or computed tomography (CT) [ 11 ] . It is critical to comprehend the comparative capability of these various imaging modalities, considering the critical role that imaging plays in predicting MVI [ 12 ] . Thus, this work aimed to evaluate the HCC radiological patterns after DAAS as well as vascular invasion of HCC after DAAs treatment via imaging by CT and MRI. METHODS Patient Enrollment This retrospective case-control investigation included 102 patients, older than 18 years, both sexes who had HCC associated with HCV. Patients were categorized into two equal groups based on their previous exposure to DAAs. Group I included patients with HCC who received DAA treatment, while Group II consisted of patients with HCC who did not receive DAA treatment (not treated). Data collected from may 2023 to December 2024 after approval from national liver institutional ethical committee (approval code: ---). Tumors other than HCC, excessive hepatic tumor infiltration, HCC mass adjacent to vital structures such as the diaphragm or central bile duct, liver transplantation, alcohol abuse, therapy drop-out, did not achieve sustained viral response, MRI contraindications [e.g., metallic implants, cardiac pacemakers, and claustrophobic patients], and severe renal insufficiency were excluded. CT contraindication: renal failure, contrast hypersensitivity Group I was administered two distinct regimens of direct-acting antiviral (DAA) dosages: one regimen consisted of sofosbuvir (400 mg) / velpatasvir (100 mg) taken daily for 12 weeks, and the other regimen involved sofosbuvir (400 mg)/daclatasvir (60 mg), also taken daily for 12 weeks. The following data reviewed from patients’ records, complete history taking, clinical examination, laboratory investigations . HCC was diagnosed with computed tomography (CT) or magnetic resonance imaging (MRI) in accordance with the management guidelines [ 14 ] . MRI Procedure Before the procedure, 57 patients in this study fasted for eight hours. A venous catheter was placed in a peripheral vein (antecubital vein in most cases), passing through along connecting tube to an automatic injector to allow easy injection. The patient was instructed on breathing hold techniques. MR imaging was performed on a high field system (GE-1.5 Tesla—general electric optima 450w,(32 channels) using a phased array coil to cover the whole liver.MR protocol used Coronal Survey BFFE, Axial T1-weighted (T1WI) images (FRFSE/PROP): Axial in-phase and out-phase gradient echo sequence (dual-FFEBH SENSE) axial images: Axial T2-weighted (ax T2 RTrprop), Coronal T2W-(FRFSE/PROSP), Axial T2 fat suppression sequence, Axial heavy T2-weighted images. Diffusion study (DW): Respiratory-triggered fat-suppressed single-shot echo-planar DW imaging was performed in the transverse plane with tri-directional diffusion gra-dients using b values 0.500 and 1200 s/mm2 to increase sensitivity to cellular packing. Dynamic study: Dynamic study was performed after bolus injection of 0.1 mmol/kg body weight of Gd-DTPA at a rate of 2 ml/s, flushed with 20 ml of sterile 0.9% saline solution from the antecubital vein. Patients were asked to hold their breath at the end of expiration CT procedure Before the procedure, 75 patients in this study fasted for eight hours. A venous catheter was placed in a peripheral vein (antecubital vein in most cases), passing through along connecting tube to an automatic injector to allow easy injection, CT procedure (Philips machine ) Dynamic CT or MRI was performed to confirm the absence of viable HCC before antiviral therapies were initiated in the DAA group. Imaging Data Analysis Images were assessed by two radiologist with more than 10 years of Experience in hepatic imaging we used established imaging pattern of lesional enhancement Typical enhancement (homogenous or heterogonous with delayed wash out) Atypical pattern of enhancement (peripheral enhancement and no arterial enhancement) Imaging pattern criteria to assess the presence of MVI in the neoplastic nodules details, All images to evaluate The following features predictive of MVI were assessed in each individual (1) tumor margins to identify those nodules with non-smooth margins (NSTM); (2) two separate imaging features(the presence of internal arteries and hypoattenuating haloes) That can help predict MVI according to a proven algorithm (3) peritumoral enhancement (PTE) become hypoattenuating on CT on arterial and delayed phase and hypointense on delayed MRI, (4) delayed enhanced capsule, The primary outcome was the microvascular invasion, portal vein invasion. The secondary outcomes were the number, size, site of lesions, metastasis Sample Size Calculation: Calculation of the sample size was performed using G*Power 3.1.9.2. (Universitat Kiel, Germany). Based on prior research [ 15 ] , number of (multiple)lesion was seen to be (53%) in DAAs group and (25.1%) in control group. The sample size was determined in accordance with the following factors: In order to mitigate the risk of turnover, the study added four cases to each group, the study used a group ratio of 1:1 and with a 95% confidence interval and an 80% power level. As a result, 51 patients were recruited for each group. Statistical analysis For the statistical analysis, we used SPSS v27 (IBM2, Armonk, NY, USA). Tests for data normality included histograms and the Shapiro-Wilks test. To analyze quantitative parametric data, we employed mean ± standard deviation (SD) and compared by the unpaired Student t-test. To analyze the qualitative variables, we employed the percentage and frequency and compared by the Chi-square test or Fisher's exact test as appropriate. It was considered statistically significant if the p-value was less than 0.05 using two-tailed tests Results Age, sex, were insignificantly different between both groups. Table 1 Table 1 Demographic data of the studied groups Group I (n = 51) Group II (n = 51) P Age (years) 58.9 ± 9.13 61.45 ± 9.1 0.161 Sex Male 31 (60.78%) 36 (70.59%) 0.297 Female 20 (39.22%) 15 (29.41%) Data are presented as mean ± SD, median (IQR) or frequency (%). Microvascular invasion occurred in 16 (31.37%) patients in group I, and in 5 (9.8%) patients in group II. Portal invasion occurred in 23 (45.1%) patients in group I, and in 9 (17.65%) patients in group II. Incidence of MVI and portal vein invasion were significantly higher in group I than group II (P < 0.05). Table 2 Table 2 Microvascular and portal vein invasion of the studied groups Group I (n = 51) Group II (n = 51) OR (95% CI) P Microvascular invasion 16 (31.37%) 5 (9.8%) 4.21 (1.41–12.59) 0.01* Portal vein invasion 23 (45.1%) 9 (17.65%) 3.83 (1.55–9.49) 0.003* *: significant as P value < 0.05. Data are presented as median (IQR) or frequency (%). Size of lesions was significantly higher in group I than group II (P < 0.05). Site of lesions was significantly different between both groups (bi-lobar was higher in group I). Focal lesions were comparable between both groups. Table 3 Table 3 Lesions characteristics of the studied groups Group I (n = 51) Group II (n = 51) P Size of lesions (cm) 14 ± 5.26 8.89 ± 5.56 < 0.001* Site of lesions Right hepatic lobe 19 (37.25%) 29 (56.86%) < 0.001* Left hepatic lobe 7 (13.73%) 6 (11.76%) Bi-lobar 25 (49.02%) 7 (13.73%) Focal lesions Multiple 17 (33.33%) 18 (35.29%) 0.835 Single 34 (66.67%) 33 (64.71%) Data are presented as median (IQR) or frequency (%). Peripheral and homogenous enhancements were insignificantly different between both groups. Heterogeneous enhancement was significantly lower in group I than group II (P < 0.001). No enhancement was significantly higher in group I than group II (P < 0.001). Nodal and pulmonary deposits were significantly higher in group I than group II (P value < 0.05). Bone deposits were comparable between both groups. Table 4 Table 4 Enhancement pattern and types of deposits of the studied groups Group I (n = 51) Group II (n = 51) P Peripheral enhancement 8 (15.69%) 2 (3.92%) 0.092 Homogenous enhancement 9 (17.65%) 11 (21.57%) 0.618 Heterogeneous enhancement 15 (29.41%) 36 (70.59%) < 0.001* No enhancement 19 (37.25%) 2 (3.92%) < 0.001* Nodal deposit 19 (37.25%) 5 (9.8%) 0.002* Pulmonary deposits 14 (27.45%) 6 (11.76%) 0.046* Bone deposits 5 (9.8%) 3 (5.88%) 0.715 *: significant as P value < 0.05. Data are presented as frequency (%). Case 1 56-year-old female patient received DAAS treatment from 2 years ago presented with abdominal pain and performed triphasic CT which shows accidentally discovered right hepatic lobe large infiltrative HCC lesion invading the right portal vein with AV fistula formation. Figure 1 Case 2 83-year-old male patient received DAAS 3 years ago presented with abdominal pain and jaundice performed dynamic MRI study showed bi-lobar multiple focal lesions presented with criteria of microvascular invasion. Figure 2 Case 3 55 year –old male had received DAAS from 2 .5 years ago performed dynamic MRI study presented with right hepatic lobe infiltrative HCC with right PV invasion and right adrenal deposits and right pulmonary deposits. Figure 3 Case 4 55 year old female patient received DAAS treatment 3 years ago undergone triphasic CT which shows hepatic focal lesion with CT criteria of microvascular invasion Fig. 4A: AXIAL arterial phase : right hepatic lobe focal lesion with non-smooth surface ( white arrow), and peritumoral enhancement ( blue arrow)B: Axial arterial phase: intra-lesional small arteries C and D: axial portovenous phase : interalesional hypoattenuating haloes: Axial portovenous phase: portahepatis large nodal deposits. DISCUSSION In HCV-induced liver cirrhosis, HCC development risk persists after viral eradication and SVR achievement [ 16 ] . Successful viral eradication causes a reduction in the probability of HCC and an alleviation in the fibrosis stage during the IFN-based therapy era [ 17 ] . The introduction of DAAs enhanced effectiveness, and improved safety profiles, initially optimistic expectations for a reduction in HCC incidence and recurrence. Yet, recent findings from literature indicated that DAAs could potentially promote tumor development in individuals with cirrhosis or in those previously treated for HCC [ 18 , 19 ] . Our results revealed that microvascular invasion occurred in 16 (31.37%) patients in DAAs group, and in 5 (9.8%) patients in control group. Portal invasion occurred in 23 (45.1%) patients in DAAs group, and in 9 (17.65%) patients in control group. Histology was used in the early diagnosis of MVI In the past, In recent years maging features have the capability for diagnosis of MVI [ 32 , 33 ] . High proportion of HCCs that developed after DAA therapy demonstrates MVI and this indicates a more aggressive tumours pattern and towards more severe clinical outcomes [ 29 ] So our findings of microvascular invasion help in taking a decision in patients that will prepared for liver transplantation for delayed starting DAAS treatment According to Pattern of HCC enhancement it was found that the presence of atypical pattern of HCC enhancement (peripheral enhancement as well as no enhanced lesions) more prominent on group 1 more than group II and this observation is very important for radiologists to know that HCC after DAAS is highly associated with atypical enhancement pattern and differentiate it from other malignant tumor from patient medical history Our study revealed aggressive pattern HCC after DAAS in the form of enlarged tumour size and PV in group I more than group II and this was in line with Also, El Fayoumie et al. [ 25 ] found that patients with HCC who received DAAs therapy had a significantly increased incidence of multifocal lesions and the infiltrative HCC pattern compared to those who did not get DAAs treatment. Recurrent HCC noted in 11.8% in HCC patients after DAAs treatment El Gazzar et al [ 34 ] stated the same results and revealed that HCC with PV invasion is distinctive of disease aggressiveness, with high chance of portal hypertension development, and poorer treatment tolerance. Limited viewpoint and therapeutic alternatives The size of lesions, MVI, portal vein invasion, nodal and pulmonary deposits were significantly raised in DAAs group than the control group. Heterogeneous enhancement was significantly decreased in DAAs group than the control group. Site of lesions was significantly different between both in DAAs and control group. Focal lesions, and bone deposits were insignificantly different between both groups. Consistent with our findings, Fouad et al. [ 15 ] stated that the lesions size was significantly higher in DAAs group than the control group. Site of lesions was significantly different between both in DAAs and control group. However, focal lesions were significantly different between both groups.. Additionally, Fatima et al. [ 26 ] demonstrated that vascular involvement reported in 28% after DAAs treatment. Our results come in line with Soliman et al. [ 27 ] who noticed that the site of lesions was significantly different between both in DAAs and control group. Focal lesions were insignificantly different between both groups. However, the size of lesions and portal vein invasion were significantly higher in DAAs group than the control group. Moreover, Abdelaziz et al. [ 28 ] demonstrated that portal vein invasion was significantly higher in DAAs group than the control group. Site of lesions was significantly different between both in DAAs and control group. Focal lesions were insignificantly different between both groups. Although, size, and site of lesions was insignificant between DAAs and control group. Focal lesions were insignificantly different between both groups. The precise mechanisms underlying the elevated frequency of tumor development or reappearance post-DAA treatment remain uncertain. One hypothesis suggests that it could stem from the disruption of the anti-tumor immune response consequent to the abrupt reduction in HCV viral load triggered by DAA, thereby facilitating tumor recurrence [ 30 ] . Early and late recurrence are both possibilities for patients undergoing treatment for HCC. Early recurrence is frequently correlated with intrinsic tumor characteristics, including tumor size, number, and stage. Conversely, late recurrence is linked to cirrhosis-related factors, including active viremia and the extent of liver deterioration [ 31 ] . This study was limited by the small sample size and the study was in a single center, retrospective nature of the study. Also, we excluded tumors other than HCC, excessive hepatic tumor infiltration, HCC mass adjacent to vital structures, liver transplantation, alcohol abuse, therapy drop-out, and severe renal insufficiency. The interpretation of imaging findings, especially in the context of post-DAA therapy, requires a high level of expertise. The changes in liver parenchyma post-therapy and the presence of cirrhosis can make it challenging to distinguish between benign and malignant vascular involvement. Conclusions: HCC after DAAS was associated with high incidence of MVI, early diagnosis of MVI is very important for prediction of early HCC recurrence and post-surgical resection poor overall survival as well as loco-regional ablation, DAAs had a potential impact on the characteristics and distribution of HCC lesions. DAAs were associated with increased in lesion size, portal vein invasion, and the presence of nodal and pulmonary deposits. Abbreviations HCC; hepatocellular carcinoma, DAAs; direct-acting antivirals, MVI; microvascular invasion CT; computed tomography, MRI; magnetic resonance imaging, PV; portal vein. PTE ; peritumoural enhancement Declarations Ethics Approval and Consent to Participate : All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (Institutional Review Board (IRB)” of National Liver Institute Menoufia University and with the Helsinki Declaration of 1964 and later versions. Committee’s reference number is 00014014 /FWA000034015 Informed consent was obtained before the study. Consent for publication : All patients included in this research gave written informed consent to publish the data contained within this study. Availability of data and materials: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Authors’ contributions : HSE writing the research, selection of research cases, prepare the figures for cases demonstration and review of the research. RAA, assess cases for initial diagnosis. SAA, assesses in cases selection and carried out cases on workstation. “All authors read and approved the final manuscript”. Competing interests : The authors declare that they have no competing interests. Funding : This study had no funding from any resource. Acknowledgments: Not Applicable. References Ducreux M, Abou-Alfa G, Bekaii-Saab T, Berlin J, Cervantes A, de Baere T, et al. The management of hepatocellular carcinoma. Current expert opinion and recommendations derived from the 24th ESMO/World congress on gastrointestinal cancer, barcelona, 2022. ESMO open. 2023;8:567-71. Ezzat R, Eltabbakh M, El Kassas M. Unique situation of hepatocellular carcinoma in Egypt: A review of epidemiology and control measures. World J Gastrointest Oncol. 2021;13:1919-38. 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Hepatocellular carcinoma in hepatitis C virus patients treated with direct acting antivirals (DAAs) and patients not exposed to DAAs: a large center comparative study .2014;10.1186/s43055-024-01249-4 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 11 Feb, 2026 Read the published version in Egyptian Journal of Radiology and Nuclear Medicine → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-6280217\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":438770294,\"identity\":\"905c72d8-a1d3-4fab-9564-1d11ee94565f\",\"order_by\":0,\"name\":\"Heba Said Ellaban\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA70lEQVRIiWNgGAWjYBACgwM8IEqCsYGBsUHiA5DJxk6KFskZIC3MxGkBqgcS0mA2QS3Hew9+/FFjITu//XDjbZtf2+T5mBkYP3zMwa3F/sy5ZGmeYxLGG84kNlvn9t02bGNmYJacuQ2PLTdyDKQZ2CQSNzAktknn9txmBGphY+bFr8X4549/Eonz+x+2SVv23LYnRouZBG+bRGLDDaAtDD9uJxLWcuZcmjVvH9AvNx42W/Y23E5uY2Zsxu+X472Hb/74Vic7vz/94Y0ff27bzm9vPvjhIx4tqICxDUw2EKseBP6QongUjIJRMApGCgAAxapXV0kCD14AAAAASUVORK5CYII=\",\"orcid\":\"\",\"institution\":\"national liver institute , menoufia university\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Heba\",\"middleName\":\"Said\",\"lastName\":\"Ellaban\",\"suffix\":\"\"},{\"id\":438770295,\"identity\":\"bb8c95af-59aa-45eb-bfe2-b747494a5d60\",\"order_by\":1,\"name\":\"Sameh Abdel Mawgoud Afify\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"national liver institute , menoufia university\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Sameh\",\"middleName\":\"Abdel Mawgoud\",\"lastName\":\"Afify\",\"suffix\":\"\"},{\"id\":438770296,\"identity\":\"a6ebefce-17b5-42fa-b2a9-f44859ae59a7\",\"order_by\":2,\"name\":\"Rasha Abdelhafiz Aly\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"national liver institute , menoufia university\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Rasha\",\"middleName\":\"Abdelhafiz\",\"lastName\":\"Aly\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2025-03-21 20:53:01\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-6280217/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-6280217/v1\",\"draftVersion\":[],\"editorialEvents\":[{\"content\":\"https://doi.org/10.1186/s43055-026-01687-2\",\"type\":\"published\",\"date\":\"2026-02-11T15:58:50+00:00\"}],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":80582130,\"identity\":\"27796fbb-b022-45de-9a2d-f00720b80de9\",\"added_by\":\"auto\",\"created_at\":\"2025-04-14 23:25:37\",\"extension\":\"jpg\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":77058,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e(A) axial CT arterial phase: large right hepatic lobe non enhanced lesion with early filling of the right portal vein denoting presence of AV fistula, (B): axial CT portovenous phase showed HCC invasion of the right PV, (C): coronal CT portovenous phase showed large amalgamated metastatic porta-hepatis lymph nodes, and (D): axial CT lower chest cuts showed posterior mediastinal metastatic lymph nodes.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"1.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6280217/v1/302df0828364cec6779bce72.jpg\"},{\"id\":80582123,\"identity\":\"05d754f7-56bd-4cc7-b0f1-0dec527df6a0\",\"added_by\":\"auto\",\"created_at\":\"2025-04-14 23:25:37\",\"extension\":\"jpg\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":69288,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e(A): axial arterial phase showed right hepatic lobe HCC lesion with peripheral non smooth surface, peripheral area of faint arterial enhancement, internal breakdowns and intra lesional small arterial branches, (B): axial delayed phase showed delayed capsular enhancement of the lesion, (C) : axial delayed phase showed delayed capsular enhancement of another smaller HCC lesion, and (D) : axial DWI sequence showed DWI restriction of the right lobe lesion as well as another smaller lesion at segment IV.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"2.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6280217/v1/37cd60113131bfd8a7c573cd.jpg\"},{\"id\":80582127,\"identity\":\"7068e8b0-1f90-4a36-8990-54f703a50d96\",\"added_by\":\"auto\",\"created_at\":\"2025-04-14 23:25:37\",\"extension\":\"jpg\",\"order_by\":3,\"title\":\"Figure 3\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":53348,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eA: axial portovenous phase showed heterogeneous right hepatic lobe (Blue arrow), right PV malignant thrombosis (white arrow), (B): axial portovenous phase showed right adrenal mass (white arrow), (C): axial lower chest cuts showed right pulmonary two pleural based nodules (deposits) , and (D):Axial DWI sequence: DWI restriction of the lesion. (Blue arrow).\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"3.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6280217/v1/36e1068b64d9225c7831debe.jpg\"},{\"id\":80582125,\"identity\":\"e2def0be-4fae-4aa8-ba1f-1c44cc9f2d1f\",\"added_by\":\"auto\",\"created_at\":\"2025-04-14 23:25:37\",\"extension\":\"jpg\",\"order_by\":4,\"title\":\"Figure 4\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":100024,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eA: AXIAL arterial phase : right hepatic lobe focal lesion with non-smooth surface ( white arrow), and peritumoral enhancement ( blue arrow)B: Axial arterial phase: intra-lesional small arteries C and D: axial portovenous phase : interalesional hypoattenuating haloes: Axial portovenous phase: portahepatis large nodal deposits.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"4.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6280217/v1/31a9421703b1dc8983bfbf68.jpg\"},{\"id\":102785525,\"identity\":\"4c6b399a-f766-4d58-89b4-f20d8c22d1c5\",\"added_by\":\"auto\",\"created_at\":\"2026-02-16 16:07:41\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":994937,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6280217/v1/8de0fadc-6388-4538-b5e1-82af0ae86d12.pdf\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"Vascular invasion in hepatocellular carcinoma developed after direct-acting antiviral therapy: CT and MRI assessment\",\"fulltext\":[{\"header\":\"BACKGROUND\",\"content\":\"\\u003cp\\u003eHepatocellular carcinoma (HCC) is the 6th most frequent malignancy and the 3rd leading reason of cancer-related mortality worldwide \\u003csup\\u003e[\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e]\\u003c/sup\\u003e. HCC is a substantial public health concern in Egypt, accounting for 33.63% of all cancers in men and 13.54% in females \\u003csup\\u003e[\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e]\\u003c/sup\\u003e. Conversely, hepatitis C virus infection (HCV) is well recognized as a prominent etiology of chronic liver disease in several countries, including Egypt, Europe, and the United States \\u003csup\\u003e[\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e]\\u003c/sup\\u003e. Annually, the risk of HCC development is between 2% and 8% in patients with HCV-associated liver cirrhosis \\u003csup\\u003e[\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e]\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eIn recent years, the introduction of new, effective IFN-free direct-acting antiviral (DAA), has significantly advanced the treatment of hepatitis C virus (HCV). These advancements have resulted in over 90% of treated patients achieving a sustained virological response (SVR), marking a significant improvement even among populations previously thought to be challenging to treat \\u003csup\\u003e[\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e]\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eEven in advanced cirrhosis, DAAs improved the treatment of chronic HCV-associated SVR with minimal contraindications and a low incidence of side effects. Nonetheless, chronic liver disease continues to increase the risk of HCC in individuals with and without a prior HCC history \\u003csup\\u003e[\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e]\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eTherefore, it is anticipated that the administration of DAAs would substantially decrease the HCC incidence and recurrence in cases with advanced fibrosis. HCV-associated cirrhosis patients may benefit from DAAs, which reported to reduce HCC risk and improve portal hypertension and fibrosis \\u003csup\\u003e[\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e]\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eIn HCC, vascular invasion is indicative of poor overall survival and recurrence. Specifically, microvascular invasion (MVI) following curative treatment is a substantial risk factor for early recurrence of HCC \\u003csup\\u003e[\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e]\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003ePrior research endeavored to construct prediction algorithms for MVI by using the radiomics method or a hybrid strategy including both radiologic characteristics and radiomics extracted from magnetic resonance imaging (MRI) or computed tomography (CT) \\u003csup\\u003e[\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e]\\u003c/sup\\u003e. It is critical to comprehend the comparative capability of these various imaging modalities, considering the critical role that imaging plays in predicting MVI \\u003csup\\u003e[\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e]\\u003c/sup\\u003e. Thus, this work aimed to evaluate the HCC radiological patterns after DAAS as well as vascular invasion of HCC after DAAs treatment via imaging by CT and MRI.\\u003c/p\\u003e\"},{\"header\":\"METHODS\",\"content\":\"\\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003ePatient Enrollment\\u003c/h2\\u003e \\u003cp\\u003eThis retrospective case-control investigation included 102 patients, older than 18 years, both sexes who had HCC associated with HCV. Patients were categorized into two equal groups based on their previous exposure to DAAs. Group I included patients with HCC who received DAA treatment, while Group II consisted of patients with HCC who did not receive DAA treatment (not treated). Data collected from may 2023 to December 2024 after approval from national liver institutional ethical committee (approval code: ---).\\u003c/p\\u003e \\u003cp\\u003eTumors other than HCC, excessive hepatic tumor infiltration, HCC mass adjacent to vital structures such as the diaphragm or central bile duct, liver transplantation, alcohol abuse, therapy drop-out, did not achieve sustained viral response, MRI contraindications [e.g., metallic implants, cardiac pacemakers, and claustrophobic patients], and severe renal insufficiency were excluded.\\u003c/p\\u003e \\u003cp\\u003eCT contraindication: renal failure, contrast hypersensitivity\\u003c/p\\u003e \\u003cp\\u003eGroup I was administered two distinct regimens of direct-acting antiviral (DAA) dosages: one regimen consisted of sofosbuvir (400 mg) / velpatasvir (100 mg) taken daily for 12 weeks, and the other regimen involved sofosbuvir (400 mg)/daclatasvir (60 mg), also taken daily for 12 weeks.\\u003c/p\\u003e \\u003cp\\u003eThe following data reviewed from patients\\u0026rsquo; records, complete history taking, clinical examination, laboratory investigations .\\u003c/p\\u003e \\u003cp\\u003eHCC was diagnosed with computed tomography (CT) or magnetic resonance imaging (MRI) in accordance with the management guidelines \\u003csup\\u003e[\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e]\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003c/div\\u003e\\n\\u003ch3\\u003eMRI Procedure\\u003c/h3\\u003e\\n\\u003cp\\u003eBefore the procedure, 57 patients in this study fasted for eight hours. A venous catheter was placed in a peripheral vein (antecubital vein in most cases), passing through along connecting tube to an automatic injector to allow easy injection. The patient was instructed on breathing hold techniques. MR imaging was performed on a high field system (GE-1.5 Tesla\\u0026mdash;general electric optima 450w,(32 channels) using a phased array coil to cover the whole\\u003c/p\\u003e \\u003cp\\u003eliver.MR protocol used Coronal Survey BFFE, Axial T1-weighted (T1WI) images (FRFSE/PROP): Axial in-phase and out-phase gradient echo sequence (dual-FFEBH SENSE) axial images: Axial T2-weighted (ax T2 RTrprop), Coronal T2W-(FRFSE/PROSP), Axial T2 fat suppression sequence, Axial heavy T2-weighted images. Diffusion study (DW): Respiratory-triggered fat-suppressed single-shot echo-planar DW imaging was performed in\\u003c/p\\u003e \\u003cp\\u003ethe transverse plane with tri-directional diffusion gra-dients using b values 0.500 and 1200 s/mm2 to increase sensitivity to cellular packing. Dynamic study: Dynamic study was performed after bolus injection of 0.1 mmol/kg body weight of Gd-DTPA at a rate of 2 ml/s, flushed with 20 ml of sterile 0.9% saline solution from the antecubital\\u003c/p\\u003e \\u003cp\\u003evein. Patients were asked to hold their breath at the end of expiration\\u003c/p\\u003e\\n\\u003ch3\\u003eCT procedure\\u003c/h3\\u003e\\n\\u003cp\\u003eBefore the procedure, 75 patients in this study fasted for eight hours. A venous catheter was placed in a peripheral vein (antecubital vein in most cases), passing through along connecting tube to an automatic injector to allow easy injection, CT procedure (Philips machine )\\u003c/p\\u003e \\u003cp\\u003eDynamic CT or MRI was performed to confirm the absence of viable HCC before antiviral therapies were initiated in the DAA group.\\u003c/p\\u003e\\n\\u003ch3\\u003eImaging Data Analysis\\u003c/h3\\u003e\\n\\u003cp\\u003eImages were assessed by two radiologist with more than 10 years of Experience in hepatic imaging we used established imaging pattern of lesional enhancement Typical enhancement (homogenous or heterogonous with delayed wash out) Atypical pattern of enhancement (peripheral enhancement and no arterial enhancement)\\u003c/p\\u003e \\u003cp\\u003eImaging pattern criteria to assess the presence of MVI in the neoplastic nodules details,\\u003c/p\\u003e \\u003cp\\u003eAll images to evaluate The following features predictive of MVI were assessed in each individual (1) tumor margins to identify those nodules with non-smooth margins (NSTM); (2) two separate imaging features(the presence of internal arteries and hypoattenuating haloes)\\u003c/p\\u003e \\u003cp\\u003eThat can help predict MVI according to a proven algorithm (3) peritumoral enhancement (PTE) become hypoattenuating on CT on arterial and delayed phase and hypointense on delayed MRI, (4) delayed enhanced capsule,\\u003c/p\\u003e \\u003cp\\u003eThe primary outcome was the microvascular invasion, portal vein invasion. The secondary outcomes were the number, size, site of lesions, metastasis\\u003c/p\\u003e\\n\\u003ch3\\u003eSample Size Calculation:\\u003c/h3\\u003e\\n\\u003cp\\u003eCalculation of the sample size was performed using G*Power 3.1.9.2. (Universitat Kiel, Germany). Based on prior research \\u003csup\\u003e[\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e]\\u003c/sup\\u003e, number of (multiple)lesion was seen to be (53%) in DAAs group and (25.1%) in control group. The sample size was determined in accordance with the following factors: In order to mitigate the risk of turnover, the study added four cases to each group, the study used a group ratio of 1:1 and with a 95% confidence interval and an 80% power level. As a result, 51 patients were recruited for each group.\\u003c/p\\u003e \\u003cdiv id=\\\"Sec8\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eStatistical analysis\\u003c/h2\\u003e \\u003cp\\u003eFor the statistical analysis, we used SPSS v27 (IBM2, Armonk, NY, USA). Tests for data normality included histograms and the Shapiro-Wilks test. To analyze quantitative parametric data, we employed mean\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;standard deviation (SD) and compared by the unpaired Student t-test. To analyze the qualitative variables, we employed the percentage and frequency and compared by the Chi-square test or Fisher's exact test as appropriate. It was considered statistically significant if the p-value was less than 0.05 using two-tailed tests\\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"Results\",\"content\":\"\\u003cp\\u003eAge, sex, were insignificantly different between both groups. Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e\\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab1\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 1\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eDemographic data of the studied groups\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"5\\\"\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c5\\\" colnum=\\\"5\\\"\\u003e\\u003c/div\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c2\\\" namest=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003eGroup I\\u003c/p\\u003e \\u003cp\\u003e(n\\u0026thinsp;=\\u0026thinsp;51)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eGroup II\\u003c/p\\u003e \\u003cp\\u003e(n\\u0026thinsp;=\\u0026thinsp;51)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003eP\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c2\\\" namest=\\\"c1\\\"\\u003e \\u003cp\\u003eAge (years)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e58.9\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;9.13\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e61.45\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;9.1\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.161\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003eSex\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eMale\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e31 (60.78%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e36 (70.59%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003e0.297\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eFemale\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e20 (39.22%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e15 (29.41%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003cp\\u003eData are presented as mean\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;SD, median (IQR) or frequency (%).\\u003c/p\\u003e \\u003cp\\u003eMicrovascular invasion occurred in 16 (31.37%) patients in group I, and in 5 (9.8%) patients in group II. Portal invasion occurred in 23 (45.1%) patients in group I, and in 9 (17.65%) patients in group II. Incidence of MVI and portal vein invasion were significantly higher in group I than group II (P\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05). Table\\u0026nbsp;\\u003cspan refid=\\\"Tab2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e\\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab2\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 2\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eMicrovascular and portal vein invasion of the studied groups\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"5\\\"\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c5\\\" colnum=\\\"5\\\"\\u003e\\u003c/div\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eGroup I\\u003c/p\\u003e \\u003cp\\u003e(n\\u0026thinsp;=\\u0026thinsp;51)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003eGroup II\\u003c/p\\u003e \\u003cp\\u003e(n\\u0026thinsp;=\\u0026thinsp;51)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eOR (95% CI)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003eP\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eMicrovascular invasion\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e16 (31.37%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e5 (9.8%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e4.21 (1.41\\u0026ndash;12.59)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003e0.01*\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003ePortal vein invasion\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e23 (45.1%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e9 (17.65%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e3.83 (1.55\\u0026ndash;9.49)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003e0.003*\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003cp\\u003e*: significant as P value\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05. Data are presented as median (IQR) or frequency (%).\\u003c/p\\u003e \\u003cp\\u003eSize of lesions was significantly higher in group I than group II (P\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05). Site of lesions was significantly different between both groups (bi-lobar was higher in group I). Focal lesions were comparable between both groups. Table\\u0026nbsp;\\u003cspan refid=\\\"Tab3\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e\\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab3\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 3\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eLesions characteristics of the studied groups\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"5\\\"\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c5\\\" colnum=\\\"5\\\"\\u003e\\u003c/div\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c2\\\" namest=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003eGroup I\\u003c/p\\u003e \\u003cp\\u003e (n\\u0026thinsp;=\\u0026thinsp;51)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eGroup II\\u003c/p\\u003e \\u003cp\\u003e (n\\u0026thinsp;=\\u0026thinsp;51)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003eP\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c2\\\" namest=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eSize of lesions (cm)\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e14\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;5.26\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e8.89\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;5.56\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003e\\u0026lt;\\u0026thinsp;0.001*\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\" morerows=\\\"2\\\" rowspan=\\\"3\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eSite of lesions\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eRight hepatic lobe\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e19 (37.25%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e29 (56.86%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\" morerows=\\\"2\\\" rowspan=\\\"3\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003e\\u0026lt;\\u0026thinsp;0.001*\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eLeft hepatic lobe\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e7 (13.73%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e6 (11.76%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eBi-lobar\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e25 (49.02%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e7 (13.73%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eFocal lesions\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eMultiple\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e17 (33.33%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e18 (35.29%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003e0.835\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eSingle\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e34 (66.67%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e33 (64.71%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003cp\\u003eData are presented as median (IQR) or frequency (%).\\u003c/p\\u003e \\u003cp\\u003ePeripheral and homogenous enhancements were insignificantly different between both groups. Heterogeneous enhancement was significantly lower in group I than group II (P\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.001). No enhancement was significantly higher in group I than group II (P\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.001). Nodal and pulmonary deposits were significantly higher in group I than group II (P value\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05). Bone deposits were comparable between both groups. Table\\u0026nbsp;\\u003cspan refid=\\\"Tab4\\\" class=\\\"InternalRef\\\"\\u003e4\\u003c/span\\u003e\\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab4\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 4\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eEnhancement pattern and types of deposits of the studied groups\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"4\\\"\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eGroup I\\u003c/p\\u003e \\u003cp\\u003e(n\\u0026thinsp;=\\u0026thinsp;51)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003eGroup II\\u003c/p\\u003e \\u003cp\\u003e(n\\u0026thinsp;=\\u0026thinsp;51)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eP\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003ePeripheral enhancement\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e8 (15.69%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e2 (3.92%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.092\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eHomogenous enhancement\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e9 (17.65%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e11 (21.57%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.618\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eHeterogeneous enhancement\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e15 (29.41%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e36 (70.59%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e\\u0026lt;\\u0026thinsp;\\u003cb\\u003e0.001*\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eNo enhancement\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e19 (37.25%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e2 (3.92%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003e\\u0026lt;\\u0026thinsp;0.001*\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eNodal deposit\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e19 (37.25%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e5 (9.8%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003e0.002*\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003ePulmonary deposits\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e14 (27.45%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e6 (11.76%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003e0.046*\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eBone deposits\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e5 (9.8%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e3 (5.88%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.715\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003cp\\u003e*: significant as P value\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05. Data are presented as frequency (%).\\u003c/p\\u003e \\u003cp\\u003e \\u003cstrong\\u003eCase 1\\u003c/strong\\u003e \\u003cp\\u003e56-year-old female patient received DAAS treatment from 2 years ago presented with abdominal pain and performed triphasic CT which shows accidentally discovered right hepatic lobe large infiltrative HCC lesion invading the right portal vein with AV fistula formation. Figure\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e\\u003c/p\\u003e \\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003e \\u003cstrong\\u003eCase 2\\u003c/strong\\u003e \\u003cp\\u003e83-year-old male patient received DAAS 3 years ago presented with abdominal pain and jaundice performed dynamic MRI study showed bi-lobar multiple focal lesions presented with criteria of microvascular invasion. Figure\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e\\u003c/p\\u003e \\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003e \\u003cstrong\\u003eCase 3\\u003c/strong\\u003e \\u003cp\\u003e55 year \\u0026ndash;old male had received DAAS from 2 .5 years ago performed dynamic MRI study presented with right hepatic lobe infiltrative HCC with right PV invasion and right adrenal deposits and right pulmonary deposits. Figure\\u0026nbsp;\\u003cspan refid=\\\"Fig3\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e\\u003c/p\\u003e \\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003e \\u003cstrong\\u003eCase 4\\u003c/strong\\u003e \\u003cp\\u003e55 year old female patient received DAAS treatment 3 years ago undergone triphasic CT which shows hepatic focal lesion with CT criteria of microvascular invasion Fig.\\u0026nbsp;4A: AXIAL arterial phase : right hepatic lobe focal lesion with non-smooth surface ( white arrow), and peritumoral enhancement ( blue arrow)B: Axial arterial phase: intra-lesional small arteries C and D: axial portovenous phase : interalesional hypoattenuating haloes: Axial portovenous phase: portahepatis large nodal deposits.\\u003c/p\\u003e \\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e\"},{\"header\":\"DISCUSSION\",\"content\":\"\\u003cp\\u003eIn HCV-induced liver cirrhosis, HCC development risk persists after viral eradication and SVR achievement \\u003csup\\u003e[\\u003cspan citationid=\\\"CR16\\\" class=\\\"CitationRef\\\"\\u003e16\\u003c/span\\u003e]\\u003c/sup\\u003e. Successful viral eradication causes a reduction in the probability of HCC and an alleviation in the fibrosis stage during the IFN-based therapy era \\u003csup\\u003e[\\u003cspan citationid=\\\"CR17\\\" class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e]\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eThe introduction of DAAs enhanced effectiveness, and improved safety profiles, initially optimistic expectations for a reduction in HCC incidence and recurrence. Yet, recent findings from literature indicated that DAAs could potentially promote tumor development in individuals with cirrhosis or in those previously treated for HCC \\u003csup\\u003e[\\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR19\\\" class=\\\"CitationRef\\\"\\u003e19\\u003c/span\\u003e]\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eOur results revealed that microvascular invasion occurred in 16 (31.37%) patients in DAAs group, and in 5 (9.8%) patients in control group. Portal invasion occurred in 23 (45.1%) patients in DAAs group, and in 9 (17.65%) patients in control group.\\u003c/p\\u003e \\u003cp\\u003eHistology was used in the early diagnosis of MVI In the past, In recent years maging features have the capability for diagnosis of MVI \\u003csup\\u003e[\\u003cspan citationid=\\\"CR32\\\" class=\\\"CitationRef\\\"\\u003e32\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR33\\\" class=\\\"CitationRef\\\"\\u003e33\\u003c/span\\u003e]\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eHigh proportion of HCCs that developed after DAA therapy demonstrates MVI and this indicates a more aggressive tumours pattern and towards more severe clinical outcomes \\u003csup\\u003e[\\u003cspan citationid=\\\"CR29\\\" class=\\\"CitationRef\\\"\\u003e29\\u003c/span\\u003e]\\u003c/sup\\u003e\\u003c/p\\u003e \\u003cp\\u003eSo our findings of microvascular invasion help in taking a decision in patients that will prepared for liver transplantation for delayed starting DAAS treatment\\u003c/p\\u003e \\u003cp\\u003eAccording to Pattern of HCC enhancement it was found that the presence of atypical pattern of HCC enhancement (peripheral enhancement as well as no enhanced lesions) more prominent on group 1 more than group II and this observation is very important for radiologists to know that HCC after DAAS is highly associated with atypical enhancement pattern and differentiate it from other malignant tumor from patient medical history\\u003c/p\\u003e \\u003cp\\u003eOur study revealed aggressive pattern HCC after DAAS in the form of enlarged tumour size and PV in group I more than group II and this was in line with Also, El Fayoumie et al. \\u003csup\\u003e[\\u003cspan citationid=\\\"CR25\\\" class=\\\"CitationRef\\\"\\u003e25\\u003c/span\\u003e]\\u003c/sup\\u003e found that patients with HCC who received DAAs therapy had a significantly increased incidence of multifocal lesions and the infiltrative HCC pattern compared to those who did not get DAAs treatment. Recurrent HCC noted in 11.8% in HCC patients after DAAs treatment\\u003c/p\\u003e \\u003cp\\u003eEl Gazzar et al \\u003csup\\u003e[\\u003cspan citationid=\\\"CR34\\\" class=\\\"CitationRef\\\"\\u003e34\\u003c/span\\u003e]\\u003c/sup\\u003e stated the same results and revealed that HCC with PV invasion is distinctive of disease aggressiveness, with high chance of portal hypertension development, and poorer treatment tolerance. Limited viewpoint and therapeutic alternatives\\u003c/p\\u003e \\u003cp\\u003eThe size of lesions, MVI, portal vein invasion, nodal and pulmonary deposits were significantly raised in DAAs group than the control group. Heterogeneous enhancement was significantly decreased in DAAs group than the control group. Site of lesions was significantly different between both in DAAs and control group. Focal lesions, and bone deposits were insignificantly different between both groups.\\u003c/p\\u003e \\u003cp\\u003eConsistent with our findings, Fouad et al. \\u003csup\\u003e[\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e]\\u003c/sup\\u003e stated that the lesions size was significantly higher in DAAs group than the control group. Site of lesions was significantly different between both in DAAs and control group. However, focal lesions were significantly different between both groups.. Additionally, Fatima et al. \\u003csup\\u003e[\\u003cspan citationid=\\\"CR26\\\" class=\\\"CitationRef\\\"\\u003e26\\u003c/span\\u003e]\\u003c/sup\\u003e demonstrated that vascular involvement reported in 28% after DAAs treatment. Our results come in line with Soliman et al. \\u003csup\\u003e[\\u003cspan citationid=\\\"CR27\\\" class=\\\"CitationRef\\\"\\u003e27\\u003c/span\\u003e]\\u003c/sup\\u003e who noticed that the site of lesions was significantly different between both in DAAs and control group. Focal lesions were insignificantly different between both groups. However, the size of lesions and portal vein invasion were significantly higher in DAAs group than the control group.\\u003c/p\\u003e \\u003cp\\u003eMoreover, Abdelaziz et al. \\u003csup\\u003e[\\u003cspan citationid=\\\"CR28\\\" class=\\\"CitationRef\\\"\\u003e28\\u003c/span\\u003e]\\u003c/sup\\u003e demonstrated that portal vein invasion was significantly higher in DAAs group than the control group. Site of lesions was significantly different between both in DAAs and control group. Focal lesions were insignificantly different between both groups. Although, size, and site of lesions was insignificant between DAAs and control group. Focal lesions were insignificantly different between both groups.\\u003c/p\\u003e \\u003cp\\u003eThe precise mechanisms underlying the elevated frequency of tumor development or reappearance post-DAA treatment remain uncertain. One hypothesis suggests that it could stem from the disruption of the anti-tumor immune response consequent to the abrupt reduction in HCV viral load triggered by DAA, thereby facilitating tumor recurrence \\u003csup\\u003e[\\u003cspan citationid=\\\"CR30\\\" class=\\\"CitationRef\\\"\\u003e30\\u003c/span\\u003e]\\u003c/sup\\u003e. Early and late recurrence are both possibilities for patients undergoing treatment for HCC. Early recurrence is frequently correlated with intrinsic tumor characteristics, including tumor size, number, and stage. Conversely, late recurrence is linked to cirrhosis-related factors, including active viremia and the extent of liver deterioration \\u003csup\\u003e[\\u003cspan citationid=\\\"CR31\\\" class=\\\"CitationRef\\\"\\u003e31\\u003c/span\\u003e]\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eThis study was limited by the small sample size and the study was in a single center, retrospective nature of the study. Also, we excluded tumors other than HCC, excessive hepatic tumor infiltration, HCC mass adjacent to vital structures, liver transplantation, alcohol abuse, therapy drop-out, and severe renal insufficiency. The interpretation of imaging findings, especially in the context of post-DAA therapy, requires a high level of expertise. The changes in liver parenchyma post-therapy and the presence of cirrhosis can make it challenging to distinguish between benign and malignant vascular involvement.\\u003c/p\\u003e \\u003cp\\u003eConclusions: HCC after DAAS was associated with high incidence of MVI, early diagnosis of MVI is very important for prediction of early HCC recurrence and post-surgical resection poor overall survival as well as loco-regional ablation, DAAs had a potential impact on the characteristics and distribution of HCC lesions. DAAs were associated with increased in lesion size, portal vein invasion, and the presence of nodal and pulmonary deposits.\\u003c/p\\u003e\"},{\"header\":\"Abbreviations\",\"content\":\"\\u003cp\\u003eHCC; hepatocellular carcinoma, DAAs; direct-acting antivirals, MVI; microvascular invasion CT; computed tomography, MRI; magnetic resonance imaging, PV; portal vein. PTE ; peritumoural enhancement\\u0026nbsp;\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eEthics Approval and Consent to Participate\\u003c/strong\\u003e: All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (Institutional Review Board (IRB)\\u0026rdquo; of National Liver Institute Menoufia University and with the Helsinki Declaration of 1964 and later versions. Committee\\u0026rsquo;s reference number is \\u003cspan dir=\\\"RTL\\\"\\u003e00014014\\u003c/span\\u003e/FWA000034015 Informed consent was obtained before the study.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConsent for publication\\u003c/strong\\u003e: All patients included in this research gave written informed consent to publish the data contained within this study.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAvailability of data and materials:\\u003c/strong\\u003e The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAuthors\\u0026rsquo; contributions\\u003c/strong\\u003e: \\u003cstrong\\u003eHSE\\u0026nbsp;\\u003c/strong\\u003ewriting the research, selection of research cases, prepare the figures for cases demonstration and review of the research. \\u003cstrong\\u003eRAA,\\u0026nbsp;\\u003c/strong\\u003eassess cases for initial diagnosis.\\u003cstrong\\u003e\\u0026nbsp;SAA,\\u0026nbsp;\\u003c/strong\\u003eassesses in cases selection and carried out cases on workstation. \\u0026ldquo;All authors read and approved the final manuscript\\u0026rdquo;.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCompeting interests\\u003c/strong\\u003e: The authors declare that they have no competing interests.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003e\\u003cspan dir=\\\"LTR\\\"\\u003eFunding\\u003c/span\\u003e\\u003c/strong\\u003e\\u003cspan dir=\\\"LTR\\\"\\u003e: This study had no funding from any resource.\\u003c/span\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAcknowledgments:\\u003c/strong\\u003e Not Applicable.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\n\\u003cli\\u003eDucreux M, Abou-Alfa G, Bekaii-Saab T, Berlin J, Cervantes A, de Baere T, et al. 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BMC Gastroenterol. 2024;24:49-55.\\u003c/li\\u003e\\n\\u003cli\\u003eLuan C-H, Su P-S, Chu C-J, Lin C-C, Su C-W, Luo J-C, et al. Analyzing risk factors and developing a stratification system for hepatocellular carcinoma recurrence after interferon-free direct-acting antiviral therapy in chronic hepatitis C patients. J Chin Med Assoc. 2024;48:97-103.\\u003c/li\\u003e\\n\\u003cli\\u003eTayyab GUN, Rasool S, Nasir B, Rubi G, Abou-Samra AB, Butt AA. Hepatocellular carcinoma occurs frequently and early after treatment in HCV genotype 3 infected persons treated with DAA regimens. BMC Gastroenterol. 2020;20:93-6.\\u003c/li\\u003e\\n\\u003cli\\u003eSharaf AL, Elbadrawy EG, Abdellatif AM, Abd Al Monem N. Frequency of hepatocellular carcinoma in cirrhotic patients after chronic hepatitis c infection treatment with direct-acting \\u0026lrm;antivirals. Afro-Egypt j infect enem dis. 2022;12:16-23.\\u003c/li\\u003e\\n\\u003cli\\u003eReig M, Boix L, Bruix J. The impact of direct antiviral agents on the development and recurrence of hepatocellular carcinoma. Liver Int. 2017;37:136-9.\\u003c/li\\u003e\\n\\u003cli\\u003eRinaldi L, Nevola R, Franci G, Perrella A, Corvino G, Marrone A, et al. Risk of hepatocellular carcinoma after HCV clearance by direct-acting antivirals treatment predictive factors and role of epigenetics. Cancers (Basel). 2020;12:321-4.\\u003c/li\\u003e\\n\\u003cli\\u003eCasey JL, Feld JJ, MacParland SA. Restoration of HCV-specific immune responses with antiviral therapy: A case for DAA treatment in acute HCV infection. Cells. 2019;8:324-8.\\u003c/li\\u003e\\n\\u003cli\\u003eVillani R, Bellanti F, Cavallone F, Di Bello G, Tamborra R, Bukke Vidyasagar N, et al. Direct-acting antivirals restore systemic redox homeostasis in chronic HCV patients. Free Radic Biol Med. 2020;156:200-6.\\u003c/li\\u003e\\n\\u003cli\\u003eLin D, Reddy V, Osman H, Lopez A, Koksal AR, Rhadhi SM, et al. Additional inhibition of Wnt/\\u0026beta;-catenin signaling by metformin in DAA treatments as a novel therapeutic strategy for HCV-infected patients. Cells. 2021;10:790-5.\\u003c/li\\u003e\\n\\u003cli\\u003eEl Fayoumie M, Abdelhady M, Gawish A, Hantour U, Abdelkhaleek I, Abdelraheem M, et al. Changing patterns of hepatocellular carcinoma after treatment with direct antiviral agents. Gastrointest Tumors. 2020;7:50-60.\\u003c/li\\u003e\\n\\u003cli\\u003eFatima T, Mumtaz H, Khan MH, Rasool S, Tayyeb M, Haider MZ, et al. Patterns of hepatocellular carcinoma after direct antiviral agents and pegylated-interferon therapy. Cureus. 2020;12:565-9.\\u003c/li\\u003e\\n\\u003cli\\u003eSoliman R, Mikhail N, Amer T, Eslam M, Shiha G. Hepatocellular carcinoma following direct acting antiviral therapy does not display an aggressive pattern: a prospective study. J Hepatol. 2020;73:622-3.\\u003c/li\\u003e\\n\\u003cli\\u003eAbdelaziz AO, Nabil MM, Abdelmaksoud AH, Shousha HI, Hashem MB, Hassan EM, et al. Tumor behavior of hepatocellular carcinoma after hepatitis C treatment by direct-acting antivirals: comparative analysis with non-direct-acting antivirals-treated patients. Eur J Gastroenterol Hepatol. 2019;31:75-9.\\u003c/li\\u003e\\n\\u003cli\\u003eRenzulli M, Buonfiglioli F, Conti F, Brocchi S, Serio I, Foschi FG, et al. Imaging features of microvascular invasion in hepatocellular carcinoma developed after direct-acting antiviral therapy in HCV-related cirrhosis. Eur Radiol. 2018;28:506-13.\\u003c/li\\u003e\\n\\u003cli\\u003eNault JC, Colombo M. Hepatocellular carcinoma and direct acting antiviral treatments: Controversy after the revolution. J Hepatol. 2016;65:663-5.\\u003c/li\\u003e\\n\\u003cli\\u003ePortolani N, Coniglio A, Ghidoni S, Giovanelli M, Benetti A, Tiberio GA, et al. Early and late recurrence after liver resection for hepatocellular carcinoma: prognostic and therapeutic implications. Ann Surg. 2006;243:229-35.\\u003c/li\\u003e\\n\\u003cli\\u003eKimH,ParkMS,ChoiJYetal.Canmicrovesselinvasion of hepatocellular carcinoma be predicted by pre-operative MRI? Eur Radiol .2009;19:1744\\u0026ndash;1751 14. \\u003c/li\\u003e\\n\\u003cli\\u003eBanerjeeS, WangDS,KimHJ etal. Acomputedtomography radiogenomic biomarker predicts microvascular invasion and clini cal outcomes in hepatocellular carcinoma. Hepatology. 2015;62:792\\u0026ndash;800\\u003c/li\\u003e\\n\\u003cli\\u003eMohamed Elgazzar, Tary Salman, Eman Abdelsameea, et al. Hepatocellular carcinoma in hepatitis C virus patients treated with direct acting antivirals (DAAs) and patients not exposed to DAAs: a large center comparative study .2014;10.1186/s43055-024-01249-4\\u003c/li\\u003e\\n\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":true,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":true,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true},\"keywords\":\"CT, DAAs, HCC, MRI, Vascular Invasion\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-6280217/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-6280217/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003ch2\\u003eBackground\\u003c/h2\\u003e \\u003cp\\u003eThe effects of direct-acting antivirals (DAAs) on vascular invasion after curative hepatocellular carcinoma (HCC) treatment remain controversial. Thus, this work aimed to assess the vascular invasion of HCC after DAAs treatment via imaging by computerized tomography (CT) and magnetic resonance imaging (MRI).\\u003c/p\\u003e\\u003ch2\\u003eMethods\\u003c/h2\\u003e \\u003cp\\u003eThis case-control study was carried out on 102 cases, 18 years or older, both sexes, with HCV-related HCC. Patients were divided into equal groups; Patients treated with DAAs (group I), and patients who were not treated with DAAs (group II). Group I received two different regimes of DAA dose, 12 weeks of sofosbuvir (400 mg)/velpatasvir (100 mg) once a day and 12 weeks of sofosubuvir 400g/daclatasvir 60g once a day.\\u003c/p\\u003e\\u003ch2\\u003eResults\\u003c/h2\\u003e \\u003cp\\u003eMicrovascular invasion occurred in 16 (31.37%) patients in group I, and in 5 (9.8%) patients in group II. Portal invasion occurred in 23 (45.1%) patients in group I, and in 9 (17.65%) patients in group II. size of lesions, no enhancement, nodal and pulmonary deposits were significantly increase in group I than group II (P\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05). Site of lesions was significantly different between both groups. Comparing group, I to group II, heterogeneous enhancement was significantly decreased (P\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.001). Focal lesions, peripheral and homogenous enhancements, and bone deposits were insignificantly different between both groups.\\u003c/p\\u003e\\u003ch2\\u003eConclusions\\u003c/h2\\u003e \\u003cp\\u003eDAAs had a potential impact on the characteristics and distribution of HCC lesions. DAAs were associated with an increase in incidence of microvascular invasion, portal vein invasion, lesion size, and the presence of nodal and pulmonary deposits.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Vascular invasion in hepatocellular carcinoma developed after direct-acting antiviral therapy: CT and MRI assessment\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2025-04-14 23:25:32\",\"doi\":\"10.21203/rs.3.rs-6280217/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"219c4ee9-3671-4945-b7ef-98dbd204aa76\",\"owner\":[],\"postedDate\":\"April 14th, 2025\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2026-02-16T16:04:45+00:00\",\"versionOfRecord\":{\"articleIdentity\":\"rs-6280217\",\"link\":\"https://doi.org/10.1186/s43055-026-01687-2\",\"journal\":{\"identity\":\"egyptian-journal-of-radiology-and-nuclear-medicine\",\"isVorOnly\":false,\"title\":\"Egyptian Journal of Radiology and Nuclear Medicine\"},\"publishedOn\":\"2026-02-11 15:58:50\",\"publishedOnDateReadable\":\"February 11th, 2026\"},\"versionCreatedAt\":\"2025-04-14 23:25:32\",\"video\":\"\",\"vorDoi\":\"10.1186/s43055-026-01687-2\",\"vorDoiUrl\":\"https://doi.org/10.1186/s43055-026-01687-2\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-6280217\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-6280217\",\"identity\":\"rs-6280217\",\"version\":[\"v1\"]},\"buildId\":\"8U1c8b4HqxoKbykW_rLl7\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}