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López-Sánchez M, Bautista-Santos A, Milke-García MDP, Allende-López A, Moreno-Alcántar R, Morán S. Nutritional Status and Incidence of Hepatocellular Carcinoma in Patients with Compensated Liver Cirrhosis. Arch Med Res 2025; 56:103127. [PMID: 39591900 DOI: 10.1016/j.arcmed.2024.103127] [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: 02/20/2024] [Revised: 10/08/2024] [Accepted: 11/07/2024] [Indexed: 11/28/2024]
Abstract
BACKGROUND Malnutrition in patients with liver cirrhosis (LC) and/or hepatocellular carcinoma (HCC) has been associated with adverse outcomes. However, there is little information on the incidence of HCC during the compensated phase of LC in relation to the nutritional status. AIM To evaluate the association between the incidence of HCC in compensated LC and their nutritional status. METHODS Patients with compensated liver cirrhosis with no previous history of ascites, hepatic encephalopathy, or variceal bleeding attending the Gastroenterology outpatient service at Centro Medico Nacional Siglo XXI were included in a prospective cohort. Clinical and nutritional parameters were collected, including the Royal Free Hospital Subjective Global Assessment (RFH-SGA) as an indicator of protein-calorie malnutrition and the triceps skinfold thickness, which classified patients as having normal subcutaneous adipose tissue (SAT), above average SAT, and below average SAT. Follow-up was censored at the time of HCC diagnosis or LC decompensation. RESULTS About 31/187 (16.0%) and 22/187 (11.8%) patients were categorized as having above- or below-average SAT at baseline, respectively. 10/187 patients (5.3%) developed HCC during the compensated phase of LC at a median of 22 months (IQR: 10.0-36.75). A higher risk of HCC was observed in subjects below average SAT (HR: 4.064, CI 95%: 1.012-16.317, p = 0.048). After adjusting the Cox models for age and α-fetoprotein at baseline, the statistical significance of the association between SAT and HCC was not modified. CONCLUSION These results suggest that decreased SAT may precede the diagnosis of HCC in compensated LC.
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Affiliation(s)
- Marlene López-Sánchez
- Laboratory of Hepatology Research, Instituto Mexicano del Seguro Social, Centro Médico Nacional Siglo XXI, Mexico City, Mexico
| | - Aleida Bautista-Santos
- Gastroenterology Service, Instituto Mexicano del Seguro Social Centro Médico Nacional Siglo XXI, Mexico City, Mexico
| | - María Del Pilar Milke-García
- Hemato-Oncology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Aldo Allende-López
- Laboratory of Hepatology Research, Instituto Mexicano del Seguro Social, Centro Médico Nacional Siglo XXI, Mexico City, Mexico
| | - Rosalba Moreno-Alcántar
- Gastroenterology Service, Instituto Mexicano del Seguro Social Centro Médico Nacional Siglo XXI, Mexico City, Mexico
| | - Segundo Morán
- Laboratory of Hepatology Research, Instituto Mexicano del Seguro Social, Centro Médico Nacional Siglo XXI, Mexico City, Mexico.
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Kim DH, Yoon JH, Choi MH, Lee CH, Kang TW, Kim HA, Ku YM, Lee JM, Kim SH, Kim KA, Lee SL, Choi JI. Comparison of non-contrast abbreviated MRI and ultrasound as surveillance modalities for HCC. J Hepatol 2024; 81:461-470. [PMID: 38636849 DOI: 10.1016/j.jhep.2024.03.048] [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: 11/30/2023] [Revised: 02/23/2024] [Accepted: 03/31/2024] [Indexed: 04/20/2024]
Abstract
BACKGROUND & AIMS Ultrasound (US) is recommended for HCC surveillance in high-risk patients but has limited performance in detecting early-stage HCC. We aimed to compare the diagnostic performance of biannual US and annual non-contrast abbreviated magnetic resonance imaging (NC-AMRI) as HCC surveillance modalities in high-risk patients. METHODS This prospective, multicenter cohort study enrolled participants with an estimated annual risk of HCC greater than 5% between October 2015 and April 2017. Participants underwent six rounds of HCC surveillance at 6-month intervals, with both US and NC-AMRI at rounds 1, 3, and 5, and only US at rounds 2, 4, and 6. The sensitivity, diagnostic yield (DY), and false referral rate (FRR) for HCC detection by US and NC-AMRI were compared. RESULTS In total, 208 participants underwent 980 US and 516 NC-AMRI examinations during 30 months of follow-up. Among them, 34 HCCs were diagnosed in 31 participants, with 20 (64.5%) classified as very early-stage and 11 (35.5%) as early-stage HCC. The sensitivity of annual NC-AMRI (71.0%, 22/31) was marginally higher than that of biannual US (45.2%, 14/31; p = 0.077). NC-AMRI showed a significantly higher DY than US (4.26% vs. 1.43%, p <0.001), with a similar FRR (2.91% vs. 3.06%, p = 0.885). A simulation of alternating US and NC-AMRI at 6-month intervals yielded a sensitivity of 83.9% (26/31), significantly exceeding that of biannual US (p = 0.006). CONCLUSIONS Annual NC-AMRI showed a marginally higher sensitivity than biannual US for HCC detection in high-risk patients. The DY of annual NC-AMRI was significantly higher than that of biannual US, without increasing the FRR. Thus, alternating US and NC-AMRI at 6-month intervals could be an optimal surveillance strategy for high-risk patients. IMPACT AND IMPLICATIONS Current guidelines permit the use of magnetic resonance imaging (MRI) as a surveillance tool for hepatocellular carcinoma in patients in whom ultrasonography (US) is inadequate. However, the specific indications, imaging sequences, and intervals for MRI surveillance remain unclear. In our study, we found that annual non-contrast abbreviated MRI exhibited marginally higher sensitivity and significantly better diagnostic yield than biannual US in patients at high risk of hepatocellular carcinoma. Alternating US and non-contrast abbreviated MRI at 6-month intervals led to significantly improved sensitivity compared to biannual US, making it a potentially optimal surveillance strategy for high-risk patients. CLINICALTRIALS GOV IDENTIFIER NCT02551250.
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Affiliation(s)
- Dong Hwan Kim
- Department of Radiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea; Current address: Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul 05505, Republic of Korea
| | - Jeong Hee Yoon
- Department of Radiology, Seoul National University Hospital and College of Medicine, Seoul National University, Seoul, Republic of Korea
| | - Moon Hyung Choi
- Department of Radiology, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Chang Hee Lee
- Department of Radiology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea
| | - Tae Wook Kang
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Hyun A Kim
- Department of Radiology, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Young-Mi Ku
- Department of Radiology, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jeong Min Lee
- Department of Radiology, Seoul National University Hospital and College of Medicine, Seoul National University, Seoul, Republic of Korea
| | - Seong Hyun Kim
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Kyung Ah Kim
- Department of Radiology, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Su Lim Lee
- Department of Radiology, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Joon-Il Choi
- Department of Radiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea.
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Fan M, Niu T, Lin B, Gao F, Tan B, Du X. Prognostic value of preoperative serum ferritin in hepatocellular carcinoma patients undergoing transarterial chemoembolization. Mol Clin Oncol 2024; 20:22. [PMID: 38357673 PMCID: PMC10865076 DOI: 10.3892/mco.2024.2720] [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: 08/16/2023] [Accepted: 01/08/2024] [Indexed: 02/16/2024] Open
Abstract
The present study investigated the prognostic impact of preoperative serum ferritin (SF) levels on the survival of patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). Clinicopathological characteristics and laboratory biomarkers of 223 patients with HCC who underwent TACE were retrospectively reviewed. The Kaplan-Meier method was used to calculate the overall survival (OS), and the log-rank test was used to evaluate statistical significance. Univariate and multivariate analyses were performed using Cox proportional hazards regression to evaluate the prognostic impact of SF in these patients. The present findings identified extrahepatic metastases [hazard ratio (HR)=0.490,95%; confidence interval (CI)=0.282-0.843; P=0.010)] and vascular invasion (HR=0.373; 95% CI=0.225-0.619; P<0.0001) as independent prognostic factors for OS. However, preoperative SF levels could not independently predict OS when compared with other prognostic factors (HR=0.810; 95% CI=0.539-1.216; P=0.309). In conclusion, preoperative SF level is an unreliable biochemical predictor of survival in patients with HCC undergoing TACE.
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Affiliation(s)
- Mi Fan
- Departmant of Oncology, NHC Key Laboratory of Nuclear Technology Medical Transformation (Mianyang Central Hospital), Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology, Mianyang, Sichuan 621000, P.R. China
- Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nan Chong, Sichuan 637000, P.R. China
| | - Tingting Niu
- Departmant of Oncology, NHC Key Laboratory of Nuclear Technology Medical Transformation (Mianyang Central Hospital), Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology, Mianyang, Sichuan 621000, P.R. China
- Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nan Chong, Sichuan 637000, P.R. China
| | - Binwei Lin
- Departmant of Oncology, NHC Key Laboratory of Nuclear Technology Medical Transformation (Mianyang Central Hospital), Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology, Mianyang, Sichuan 621000, P.R. China
| | - Feng Gao
- Departmant of Oncology, NHC Key Laboratory of Nuclear Technology Medical Transformation (Mianyang Central Hospital), Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology, Mianyang, Sichuan 621000, P.R. China
| | - Bangxian Tan
- Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nan Chong, Sichuan 637000, P.R. China
| | - Xiaobo Du
- Departmant of Oncology, NHC Key Laboratory of Nuclear Technology Medical Transformation (Mianyang Central Hospital), Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology, Mianyang, Sichuan 621000, P.R. China
- Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nan Chong, Sichuan 637000, P.R. China
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Decharatanachart P, Pan-ngum W, Peeraphatdit T, Tanpowpong N, Tangkijvanich P, Treeprasertsuk S, Rerknimitr R, Chaiteerakij R. Cost-Utility Analysis of Non-Contrast Abbreviated Magnetic Resonance Imaging for Hepatocellular Carcinoma Surveillance in Cirrhosis. Gut Liver 2024; 18:135-146. [PMID: 37560799 PMCID: PMC10791494 DOI: 10.5009/gnl230089] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 05/01/2023] [Accepted: 05/23/2023] [Indexed: 08/11/2023] Open
Abstract
BACKGROUND/AIMS Ultrasonography has a low sensitivity for detecting early-stage hepatocellular carcinoma (HCC) in cirrhotic patients. Non-contrast abbreviated magnetic resonance imaging (aMRI) demonstrated a comparable performance to that of magnetic resonance imaging without the risk of contrast media exposure and at a lower cost than that of full diagnostic MRI. We aimed to investigate the cost-effectiveness of non-contrast aMRI for HCC surveillance in cirrhotic patients, using ultrasonography with alpha-fetoprotein (AFP) as a reference. METHODS Cost-utility analysis was performed using a Markov model in Thailand and the United States. Incremental cost-effectiveness ratios were calculated using the total costs and quality-adjusted life years (QALYs) gained in each strategy. Surveillance protocols were considered cost-effective based on a willingness-to-pay value of $4,665 (160,000 Thai Baht) in Thailand and $50,000 in the United States. RESULTS aMRI was cost-effective in both countries with incremental cost-effectiveness ratios of $3,667/QALY in Thailand and $37,062/QALY in the United States. Patient-level microsimulations showed consistent findings that aMRI was cost-effective in both countries. By probabilistic sensitivity analysis, aMRI was found to be more cost-effective than combined ultrasonography and AFP with a probability of 0.77 in Thailand and 0.98 in the United States. By sensitivity analyses, annual HCC incidence was revealed as the most influential factor affecting cost-effectiveness. The cost-effectiveness of aMRI increased in settings with a higher HCC incidence. At a higher HCC incidence, aMRI would remain cost-effective at a higher aMRI-to-ultrasonography with AFP cost ratio. CONCLUSIONS Compared to ultrasonography with AFP, non-contrast aMRI is a cost-effective strategy for HCC surveillance and may be useful for such surveillance in cirrhotic patients, especially in those with high HCC risks.
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Affiliation(s)
| | - Wirichada Pan-ngum
- Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Thoetchai Peeraphatdit
- Division of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Natthaporn Tanpowpong
- Department of Radiology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Pisit Tangkijvanich
- Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Sombat Treeprasertsuk
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Rungsun Rerknimitr
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
- Center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Roongruedee Chaiteerakij
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
- Center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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Allaire M, Thabut D. Portal hypertension and variceal bleeding in patients with liver cancer: Evidence gaps for prevention and management. Hepatology 2024; 79:213-223. [PMID: 36631021 DOI: 10.1097/hep.0000000000000291] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 12/19/2022] [Indexed: 01/13/2023]
Abstract
BACKGROUND AND AIMS Portal hypertension (PHT) and HCC are 2 major complications of cirrhosis that often coexist in the same patient and impact the prognosis, especially in patients with acute variceal bleeding. In this review, we aim to discuss the best strategy for PHT screening and primary prophylaxis, as well as the management of acute variceal bleeding, to improve the management of PHT in HCC patients. RESULTS Recent therapeutic advances observed in the management of HCC, notably through the advent of immunotherapy, have led to a clear improvement in the survival of patients. The prevention of complications related to underlying cirrhosis, such as PHT and acute variceal bleeding, is now part of the management of HCC patients. The Baveno VII conference recently redefined screening and prophylaxis in patients with cirrhosis. However, data regarding the applicability of these criteria in patients with HCC have been sparse. From our point of view, the Baveno criteria are not appropriate to exclude high-risk esophageal varices (EV) in HCC patients, and endoscopy should be performed except in HCC patients with a liver stiffness measurement (LSM) ≥25 kPa, who should benefit from nonselective beta-blockers (NSSBs) without performing endoscopy. We are also in favor of using NSBBs as primary prophylaxis in patients with EV regardless of the size and with gastric varices since these patients display clinically significant PHT. CONCLUSIONS Appropriate evaluation and treatment of PHT remain major issues in improving the outcomes of HCC patients. Many questions remain unanswered, opening the field to many areas of research.
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Affiliation(s)
- Manon Allaire
- AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service d'Hépato-gastroentérologie, Paris, France
- Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, Team Proliferation Stress and Liver Physiopathology, Paris, France
| | - Dominique Thabut
- AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service d'Hépato-gastroentérologie, Paris, France
- Sorbonne Université, INSERM, Centre de recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
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Fukui S, Wada H, Ikeda K, Kobayashi M, Shimada Y, Nakazawa Y, Mizutani H, Ichikawa Y, Nishiura Y, Moritani I, Yamanaka Y, Inoue H, Shimaoka M, Shimpo H, Shiraki K. Detection of a Prethrombotic State in Patients with Hepatocellular Carcinoma, Using a Clot Waveform Analysis. Clin Appl Thromb Hemost 2024; 30:10760296241246002. [PMID: 38591954 PMCID: PMC11005492 DOI: 10.1177/10760296241246002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Revised: 03/14/2024] [Accepted: 03/21/2024] [Indexed: 04/10/2024] Open
Abstract
Background: Although hepatocellular carcinoma (HCC) is frequently associated with thrombosis, it is also associated with liver cirrhosis (LC) which causes hemostatic abnormalities. Therefore, hemostatic abnormalities in patients with HCC were examined using a clot waveform analysis (CWA). Methods: Hemostatic abnormalities in 88 samples from HCC patients, 48 samples from LC patients and 153 samples from patients with chronic liver diseases (CH) were examined using a CWA-activated partial thromboplastin time (APTT) and small amount of tissue factor induced FIX activation (sTF/FIXa) assay. Results: There were no significant differences in the peak time on CWA-APTT among HCC, LC, and CH, and the peak heights of CWA-APTT were significantly higher in HCC and CH than in HVs and LC. The peak heights of the CWA-sTF/FIXa were significantly higher in HCC than in LC. The peak times of the CWA-APTT were significantly longer in stages B, C, and D than in stage A or cases of response. In the receiver operating characteristic (ROC) curve, the fibrin formation height (FFH) of the CWA-APTT and CWA-sTF/FIXa showed the highest diagnostic ability for HCC and LC, respectively. Thrombosis was observed in 13 HCC patients, and arterial thrombosis and portal vein thrombosis were frequently associated with HCC without LC and HCC with LC, respectively. In ROC, the peak time×peak height of the first derivative on the CWA-sTF/FIXa showed the highest diagnostic ability for thrombosis. Conclusion: The CWA-APTT and CWA-sTF/FIXa can increase the evaluability of HCC including the association with LC and thrombotic complications.
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Affiliation(s)
- Shunsuke Fukui
- Research Center, Mie Prefectural General Medical Center, Yokkaichi, Japan
| | - Hideo Wada
- Research Center, Mie Prefectural General Medical Center, Yokkaichi, Japan
- Department of General and Laboratory Medicine, Mie Prefectural General Medical Center, Yokkaichi, Japan
| | - Kohei Ikeda
- Research Center, Mie Prefectural General Medical Center, Yokkaichi, Japan
| | - Mayu Kobayashi
- Department of Gastroenterology, Mie Prefectural General Medical Center, Yokkaichi, Japan
| | - Yasuaki Shimada
- Department of Gastroenterology, Mie Prefectural General Medical Center, Yokkaichi, Japan
| | - Yuuichi Nakazawa
- Department of Gastroenterology, Mie Prefectural General Medical Center, Yokkaichi, Japan
| | - Hiroki Mizutani
- Department of Gastroenterology, Mie Prefectural General Medical Center, Yokkaichi, Japan
| | - Yuhuko Ichikawa
- Department of Central Laboratory Medicine, Mie Prefectural General Medical Center, Yokkaichi, Japan
| | - Yuuki Nishiura
- Department of Gastroenterology, Mie Prefectural General Medical Center, Yokkaichi, Japan
| | - Isao Moritani
- Department of Gastroenterology, Mie Prefectural General Medical Center, Yokkaichi, Japan
| | - Yutaka Yamanaka
- Department of Gastroenterology, Mie Prefectural General Medical Center, Yokkaichi, Japan
| | - Hidekazu Inoue
- Department of Gastroenterology, Mie Prefectural General Medical Center, Yokkaichi, Japan
| | - Motomu Shimaoka
- Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, Tsu, Japan
| | - Hideto Shimpo
- Mie Prefectural General Medical Center, Yokkaichi, Japan
| | - Katsuya Shiraki
- Research Center, Mie Prefectural General Medical Center, Yokkaichi, Japan
- Department of General and Laboratory Medicine, Mie Prefectural General Medical Center, Yokkaichi, Japan
- Department of Gastroenterology, Mie Prefectural General Medical Center, Yokkaichi, Japan
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Fraile-López M, Alvarez-Navascués C, González-Diéguez ML, Cadahía V, Chiminazzo V, Castaño A, Varela M, Rodríguez M. Predictive models for hepatocellular carcinoma development after sustained virological response in advanced hepatitis C. GASTROENTEROLOGIA Y HEPATOLOGIA 2023; 46:754-763. [PMID: 36716928 DOI: 10.1016/j.gastrohep.2023.01.008] [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: 08/18/2022] [Revised: 12/07/2022] [Accepted: 01/21/2023] [Indexed: 02/01/2023]
Abstract
BACKGROUND & AIMS Life-long hepatocellular carcinoma (HCC) surveillance is recommended after sustained virological response (SVR) in patients with advanced hepatitis C. Since the identification of patients who could be safely discontinued for surveillance is essential, we aimed to identify subsets of patients with low-risk HCC. METHODS 491 patients with advanced and compensated fibrosis (≥F3) were prospectively followed after achieving SVR with interferon-free therapies. Clinical-biological parameters and liver stiffness measurement (LSM) were performed before starting treatment (ST) and at SVR, and HCC surveillance was carried out. RESULTS During a median follow-up of 49.8 months, 29 (5.9%) patients developed HCC [incidence rate: 1.6/100 patient-years (PYs)]. Two predictive models based on LSM (Model-A) or FIB-4 score (Model-B) were proposed. Only SVR parameters were included in the models, because they showed a higher accuracy for predicting HCC than ST measurements. Variables independently associated with HCC were LSM (HR, 1.03; 95% CI, 1.01-1.05), age (HR, 1.04; 95% CI, 1.01-1.08) and albumin levels (HR, 0.90; 95% CI, 0.84-0.97) in Model-A, and FIB-4 (HR, 1.22; 95% CI, 1.08-1.37) and albumin (HR, 0.90; 95% CI, 0.84-0.97) in model-B. Both models allow HCC risk stratification, identifying low-risk groups with an HCC incidence rate of 0.16/100 and 0.25/100 PYs, respectively. An overall increased hazard of HCC was observed over time. CONCLUSION Simple models based on non-invasive markers of liver fibrosis, LSM or FIB-4, together with age and albumin levels at SVR permit to identify subsets of patients with HCC risk clearly <1%/year, for whom HCC surveillance might not be cost-effective.
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Affiliation(s)
- Miguel Fraile-López
- Liver Unit, Division of Gastroenterology & Hepatology, Hospital Universitario Central de Asturias, Oviedo, Spain.
| | - Carmen Alvarez-Navascués
- Liver Unit, Division of Gastroenterology & Hepatology, Hospital Universitario Central de Asturias, Oviedo, Spain; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
| | - María Luisa González-Diéguez
- Liver Unit, Division of Gastroenterology & Hepatology, Hospital Universitario Central de Asturias, Oviedo, Spain
| | - Valle Cadahía
- Liver Unit, Division of Gastroenterology & Hepatology, Hospital Universitario Central de Asturias, Oviedo, Spain
| | - Valentina Chiminazzo
- Plataforma de Bioestadística y Epidemiología del Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain
| | - Andrés Castaño
- Liver Unit, Division of Gastroenterology & Hepatology, Hospital Universitario Central de Asturias, Oviedo, Spain
| | - María Varela
- Liver Unit, Division of Gastroenterology & Hepatology, Hospital Universitario Central de Asturias, Oviedo, Spain; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain; Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Oviedo, Spain; University of Oviedo, Oviedo, Spain
| | - Manuel Rodríguez
- Liver Unit, Division of Gastroenterology & Hepatology, Hospital Universitario Central de Asturias, Oviedo, Spain; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain; University of Oviedo, Oviedo, Spain
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8
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Rabaan AA, Bello KE, Irekeola AA, Kaabi NAA, Halwani MA, Yousuf AA, Alshengeti A, Alfaraj AH, Khamis F, Al-Subaie MF, AlShehail BM, Almuthree SA, Ibraheem NY, Khalifa MH, Alfaresi M, Fares MAA, Garout M, Alsayyah A, Alshehri AA, Alqahtani AS, Alissa M. Prevalence of Hepatocellular Carcinoma in Hepatitis B Population within Southeast Asia: A Systematic Review and Meta-Analysis of 39,050 Participants. Pathogens 2023; 12:1220. [PMID: 37887736 PMCID: PMC10609743 DOI: 10.3390/pathogens12101220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Revised: 09/09/2023] [Accepted: 10/02/2023] [Indexed: 10/28/2023] Open
Abstract
BACKGROUND AND AIM Hepatocellular carcinoma (HCC) is a significant complication of hepatitis B and still poses a global public health concern. This systematic review and meta-analysis provide adequate details on the prevalence of HCC in the HBV population within Southeast Asian countries. METHOD Following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) criteria, a thorough search for literature discussing the prevalence of HCC in the HBV population within southeast Asia was performed. Eligible studies were subjected to a meta-analysis utilising a DerSimonian and Laird approach and a random effect model. A protocol was registered with PROSPERO (CRD42023423953). RESULT Our study meticulously recovered 41 articles from seven countries in Southeast Asia, namely Cambodia, Indonesia, Malaysia, the Philippines, Singapore, Thailand, and Vietnam. A total of 39,050 HBV patients and 7479 HCC cases in southeast Asia were analysed. The pooled prevalence of HCC in HBV cases within southeast Asia was 45.8% (95% CI, 34.3-57.8%, I2 = 99.51%, p < 0.001). Singapore (62.5%, CI: 42.4-79.1) had the highest pooled prevalence of HCC in the HBV population compared to Vietnam, with the lowest estimate (22.4%, CI: 9.9-44.9). There was a drop in the pooled prevalence of HCC in HBV from 2016 until now (37.6%, CI: 19.2-60.5). CONCLUSION The findings of this review reveal a high pooled prevalence of HCC in the HBV population and therefore stir the need for routine screening, management, and surveillance.
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Affiliation(s)
- Ali A. Rabaan
- Molecular Diagnostic Laboratory, Johns Hopkins Aramco Healthcare, Dhahran 31311, Saudi Arabia
- College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia
- Department of Public Health and Nutrition, The University of Haripur, Haripur 22610, Pakistan
| | - Kizito Eneye Bello
- Department of Microbiology, Faculty of Natural Science, Kogi State University (Prince Abubakar Audu University) Anyigba, Anyigba PMB 1008, Nigeria
- Department of Medical Microbiology and Parasitology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia
| | - Ahmad Adebayo Irekeola
- Department of Medical Microbiology and Parasitology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia
- Microbiology Unit, Department of Biological Sciences, College of Natural and Applied Sciences, Summit University Offa, Offa PMB 4412, Nigeria
| | - Nawal A. Al Kaabi
- College of Medicine and Health Science, Khalifa University, Abu Dhabi 127788, United Arab Emirates
- Sheikh Khalifa Medical City, Abu Dhabi Health Services Company (SEHA), Abu Dhabi 51900, United Arab Emirates
| | - Muhammad A. Halwani
- Department of Medical Microbiology, Faculty of Medicine, Al Baha University, Al Baha 4781, Saudi Arabia
| | - Amjad A. Yousuf
- Department of Medical Laboratories Technology, College of Applied Medical Sciences, Taibah University, Madinah 41411, Saudi Arabia
| | - Amer Alshengeti
- Department of Pediatrics, College of Medicine, Taibah University, Al-Madinah 41491, Saudi Arabia
- Department of Infection Prevention and Control, Prince Mohammad Bin Abdulaziz Hospital, National Guard Health Affairs, Al-Madinah 41491, Saudi Arabia
| | - Amal H. Alfaraj
- Pediatric Department, Abqaiq General Hospital, First Eastern Health Cluster, Abqaiq 33261, Saudi Arabia
| | - Faryal Khamis
- Infection Diseases Unit, Department of Internal Medicine, Royal Hospital, Muscat 1331, Oman
| | - Maha F. Al-Subaie
- College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia
- Research Center, Dr. Sulaiman Alhabib Medical Group, Riyadh 13328, Saudi Arabia
- Department of Infectious Diseases, Dr. Sulaiman Alhabib Medical Group, Riyadh 13328, Saudi Arabia
| | - Bashayer M. AlShehail
- Pharmacy Practice Department, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia
| | - Souad A. Almuthree
- Department of Infectious Disease, King Abdullah Medical City, Makkah 43442, Saudi Arabia
| | - Noha Y. Ibraheem
- Department of Infectious Disease, King Abdullah Medical City, Makkah 43442, Saudi Arabia
| | - Mahassen H. Khalifa
- Department of Infectious Disease, King Abdullah Medical City, Makkah 43442, Saudi Arabia
| | - Mubarak Alfaresi
- Department of Pathology and Laboratory Medicine, Zayed Military Hospital, Abu Dhabi 3740, United Arab Emirates
- Department of Pathology, College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai 505055, United Arab Emirates
| | - Mona A. Al Fares
- Department of Internal Medicine, King Abdulaziz University Hospital, Jeddah 21589, Saudi Arabia
| | - Mohammed Garout
- Department of Community Medicine and Health Care for Pilgrims, Faculty of Medicine, Umm Al-Qura University, Makkah 21955, Saudi Arabia
| | - Ahmed Alsayyah
- Department of Pathology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia
| | - Ahmad A. Alshehri
- Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Najran University, Najran 61441, Saudi Arabia
| | - Ali S. Alqahtani
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Khalid University, Abha 61481, Saudi Arabia
| | - Mohammed Alissa
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
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9
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Omar A, Kaseb A, Elbaz T, El-Kassas M, El Fouly A, Hanno AF, El Dorry A, Hosni A, Helmy A, Saad AS, Alolayan A, Eysa BE, Hamada E, Azim H, Khattab H, Elghazaly H, Tawfik H, Ayoub H, Khaled H, Saadeldin I, Waked I, Barakat EMF, El Meteini M, Hamed Shaaban M, EzzElarab M, Fathy M, Shaker M, Sobhi M, Shaker MK, ElGharib M, Abdullah M, Mokhtar M, Elshazli M, Heikal OMK, Hetta O, ElWakil RM, Abdel Wahab S, Eid SS, Rostom Y. Egyptian Society of Liver Cancer Recommendation Guidelines for the Management of Hepatocellular Carcinoma. J Hepatocell Carcinoma 2023; 10:1547-1571. [PMID: 37744303 PMCID: PMC10516190 DOI: 10.2147/jhc.s404424] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Accepted: 09/01/2023] [Indexed: 09/26/2023] Open
Abstract
Globally, hepatocellular carcinoma (HCC) is the fourth most common cause of death from cancer. The prevalence of this pathology, which has been on the rise in the last 30 years, has been predicted to continue increasing. HCC is the most common cause of cancer-related morbidity and mortality in Egypt and is also the most common cancer in males. Chronic liver diseases, including chronic hepatitis C, which is a primary health concern in Egypt, are considered major risk factors for HCC. However, HCC surveillance is recommended for patients with chronic hepatitis B virus (HBV) and liver cirrhosis; those above 40 with HBV but without cirrhosis; individuals with hepatitis D co-infection or a family history of HCC; and Nonalcoholic fatty liver disease (NAFLD) patients exhibiting significant fibrosis or cirrhosis. Several international guidelines aid physicians in the management of HCC. However, the availability and cost of diagnostic modalities and treatment options vary from one country to another. Therefore, the current guidelines aim to standardize the management of HCC in Egypt. The recommendations presented in this report represent the current management strategy at HCC treatment centers in Egypt. Recommendations were developed by an expert panel consisting of hepatologists, oncologists, gastroenterologists, surgeons, pathologists, and radiologists working under the umbrella of the Egyptian Society of Liver Cancer. The recommendations, which are based on the currently available local diagnostic aids and treatments in the country, include recommendations for future prospects.
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Affiliation(s)
- Ashraf Omar
- Department of Gastroenterology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed Kaseb
- Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Tamer Elbaz
- Department of Gastroenterology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed El-Kassas
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Amr El Fouly
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Abdel Fatah Hanno
- Department of Gastroenterology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Ahmed El Dorry
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Ahmed Hosni
- Department of Interventional Radiology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Amr Helmy
- Department of Surgery, National Liver Institute Menoufia University, Menoufia, Egypt
| | - Amr S Saad
- Department of Oncology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Ashwaq Alolayan
- Department of Oncology, National Guard Hospital, Riyadh, Saudi Arabia
| | - Basem Elsayed Eysa
- Department of Gastroenterology, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Emad Hamada
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hamdy Azim
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hany Khattab
- Department of Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hesham Elghazaly
- Department of Oncology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Hesham Tawfik
- Department of Oncology, Faculty of Medicine, Tanta University, TantaEgypt
| | - Hisham Ayoub
- Department of Gastroenterology, Military Medical Academy, Cairo, Egypt
| | - Hussein Khaled
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ibtessam Saadeldin
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Imam Waked
- Department of Gastroenterology, Menoufia Liver Institute, Menoufia, Egypt
| | - Eman M F Barakat
- Department of Gastroenterology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mahmoud El Meteini
- Department of Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed Hamed Shaaban
- Department of Interventional Radiology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed EzzElarab
- Department of Gastroenterology, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Mohamed Fathy
- Department of Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed Shaker
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed Sobhi
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed Kamal Shaker
- Department of Gastroenterology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed ElGharib
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohammed Abdullah
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohesn Mokhtar
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mostafa Elshazli
- Department of Surgery, Faculty of Medicine, Cairo University, Cairo, Egypt
| | | | - Osama Hetta
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Reda Mahmoud ElWakil
- Department of Gastroenterology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Sameh Abdel Wahab
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Samir Shehata Eid
- Department of Oncology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Yousri Rostom
- Department of Oncology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - On behalf of the Egyptian Liver Cancer Committee Study Group
- Department of Gastroenterology, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo, Egypt
- Department of Gastroenterology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Department of Interventional Radiology, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of Surgery, National Liver Institute Menoufia University, Menoufia, Egypt
- Department of Oncology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Department of Oncology, National Guard Hospital, Riyadh, Saudi Arabia
- Department of Gastroenterology, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of Oncology, Faculty of Medicine, Tanta University, TantaEgypt
- Department of Gastroenterology, Military Medical Academy, Cairo, Egypt
- Department of Gastroenterology, Menoufia Liver Institute, Menoufia, Egypt
- Department of Gastroenterology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Department of Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Department of Surgery, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of Oncology, Faculty of Medicine, Assiut University, Assiut, Egypt
- Department of Oncology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
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10
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Gupta R, Kadhim MM, Turki Jalil A, Obayes AM, Aminov Z, Alsaikhan F, Ramírez-Coronel AA, Ramaiah P, Tayyib NA, Luo X. Multifaceted role of NF-κB in hepatocellular carcinoma therapy: Molecular landscape, therapeutic compounds and nanomaterial approaches. ENVIRONMENTAL RESEARCH 2023; 228:115767. [PMID: 36966991 DOI: 10.1016/j.envres.2023.115767] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Revised: 03/20/2023] [Accepted: 03/22/2023] [Indexed: 05/16/2023]
Abstract
The predominant kind of liver cancer is hepatocellular carcinoma (HCC) that its treatment have been troublesome difficulties for physicians due to aggressive behavior of tumor cells in proliferation and metastasis. Moreover, stemness of HCC cells can result in tumor recurrence and angiogenesis occurs. Another problem is development of resistance to chemotherapy and radiotherapy in HCC cells. Genomic mutations participate in malignant behavior of HCC and nuclear factor-kappaB (NF-κB) has been one of the oncogenic factors in different human cancers that after nuclear translocation, it binds to promoter of genes in regulating their expression. Overexpression of NF-κB has been well-documented in increasing proliferation and invasion of tumor cells and notably, when its expression enhances, it induces chemoresistance and radio-resistance. Highlighting function of NF-κB in HCC can shed some light on the pathways regulating progression of tumor cells. The first aspect is proliferation acceleration and apoptosis inhibition in HCC cells mediated by enhancement in expression level of NF-κB. Moreover, NF-κB is able to enhance invasion of HCC cells via upregulation of MMPs and EMT, and it triggers angiogenesis as another step for increasing spread of tumor cells in tissues and organs. When NF-κB expression enhances, it stimulates chemoresistance and radio-resistance in HCC cells and by increasing stemness and population of cancer-stem cells, it can provide the way for recurrence of tumor. Overexpression of NF-κB mediates therapy resistance in HCC cells and it can be regulated by non-coding RNAs in HCC. Moreover, inhibition of NF-κB by anti-cancer and epigenetic drugs suppresses HCC tumorigenesis. More importantly, nanoparticles are considered for suppressing NF-κB axis in cancer and their prospectives and results can also be utilized for treatment of HCC. Nanomaterials are promising factors in treatment of HCC and by delivery of genes and drugs, they suppress HCC progression. Furthermore, nanomaterials provide phototherapy in HCC ablation.
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Affiliation(s)
- Reena Gupta
- Institute of Pharmaceutical Research, GLA University, District-Mathura, U. P., India
| | - Mustafa M Kadhim
- Department of Dentistry, Kut University College, Kut, Wasit, 52001, Iraq; Medical Laboratory Techniques Department, Al-Farahidi University, Baghdad, 10022, Iraq
| | - Abduladheem Turki Jalil
- Medical Laboratories Techniques Department, Al-Mustaqbal University College, Babylon, Hilla, 51001, Iraq.
| | | | - Zafar Aminov
- Department of Public Health and Healthcare Management, Samarkand State Medical University, 18 Amir Temur Street, Samarkand, Uzbekistan; Department of Scientific Affairs, Tashkent State Dental Institute, 103 Makhtumkuli Str., Tashkent, Uzbekistan
| | - Fahad Alsaikhan
- College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj, Saudi Arabia.
| | - Andrés Alexis Ramírez-Coronel
- Azogues Campus Nursing Career, Health and Behavior Research Group (HBR), Psychometry and Ethology Laboratory, Catholic University of Cuenca, Ecuador; Epidemiology and Biostatistics Research Group, CES University, Colombia; Educational Statistics Research Group (GIEE), National University of Education, Ecuador
| | | | - Nahla A Tayyib
- Faculty of Nursing, Umm al- Qura University, Makkah, Saudi Arabia
| | - Xuanming Luo
- Department of General Surgery, Shanghai Xuhui Central Hospital, Fudan University, Shanghai, 200031, China.
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11
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Yu SJ, Yoo JJ, Lee DH, Kim SJ, Cho EJ, Kim SH, Lee JH, Kim YJ, Lee JM, Lee JY, Yoon JH. Adding MRI as a Surveillance Test for Hepatocellular Carcinoma in Patients with Liver Cirrhosis Can Improve Prognosis. Biomedicines 2023; 11:382. [PMID: 36830919 PMCID: PMC9953123 DOI: 10.3390/biomedicines11020382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Revised: 01/23/2023] [Accepted: 01/25/2023] [Indexed: 02/01/2023] Open
Abstract
Gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) can detect early stages of hepatocellular carcinoma (HCC). However, the survival benefit of Gd-EOB-DTPA-enhanced MRI in the surveillance of patients with cirrhosis has not yet been determined. We explored whether the intermittent replacement of ultrasonography (USG) with Gd-EOB-DTPA-enhanced MRI during HCC surveillance improved the clinical outcomes of patients with cirrhosis. We performed a retrospective cohort study of 421 HCC patients who were newly diagnosed during surveillance. Of these patients, 126 (29.9%) underwent surveillance based on Gd-EOB-DTPA-enhanced MRI and USG (USG+MRI group). The patients (295, 70.1%) who did not undergo MRI during surveillance were referred to as the USG group. In the USG+MRI group, 120 (95.2%) of 126 patients were diagnosed with early-stage HCC, whereas 247 (83.7%) of 295 patients were diagnosed with early-stage HCC in the USG group (P = 0.009). The significantly longer overall survival and time to progression in patients in the USG+MRI group compared to the unmatched cohort USG group was consistently observed by inverse probability weighting and propensity score-matched analysis. Gd-EOB-DTPA-enhanced MRI combined surveillance improved the detection of early-stage HCC and clinical outcomes such as overall survival and the time to progression in patients with cirrhosis.
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Affiliation(s)
- Su Jong Yu
- Department of Internal Medicine and Liver Research Institute, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea
| | - Jeong-Ju Yoo
- Department of Internal Medicine, Soonchunhyaung University, Bucheon Hospital, Bucheon 14584, Republic of Korea
| | - Dong Ho Lee
- Department of Radiology and Institute of Radiation Medicine, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea
| | - Su Jin Kim
- Department of Statistics, Soonchunhyaung University, Bucheon Hospital, Bucheon 14584, Republic of Korea
| | - Eun Ju Cho
- Department of Internal Medicine and Liver Research Institute, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea
| | - Se Hyung Kim
- Department of Radiology and Institute of Radiation Medicine, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea
| | - Yoon Jun Kim
- Department of Internal Medicine and Liver Research Institute, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea
| | - Jeong Min Lee
- Department of Radiology and Institute of Radiation Medicine, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea
| | - Jae Young Lee
- Department of Radiology and Institute of Radiation Medicine, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea
| | - Jung-Hwan Yoon
- Department of Internal Medicine and Liver Research Institute, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea
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12
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Yan LJ, Yao SY, Li HC, Meng GX, Liu KX, Ding ZN, Hong JG, Chen ZQ, Dong ZR, Li T. Efficacy and Safety of Aspirin for Prevention of Hepatocellular Carcinoma: An Updated Meta-analysis. J Clin Transl Hepatol 2022; 10:835-846. [PMID: 36304506 PMCID: PMC9547262 DOI: 10.14218/jcth.2021.00257] [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: 07/01/2021] [Revised: 09/30/2021] [Accepted: 12/15/2021] [Indexed: 12/04/2022] Open
Abstract
BACKGROUND AND AIMS Previous meta-analyses have shown that aspirin use may reduce the risk of hepatocellular carcinoma (HCC). However, the optimal dose, frequency, and duration of aspirin use or the safety and efficacy of aspirin in target populations for HCC prevention remain unclear. The study aim was to investigate the efficacy and safety of aspirin for prevention of HCC. METHODS Publications were retrieved by a comprehensive literature research of several databases. Based on a random-effects model, hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were used to assess the pooled risk. The dose-response relationship between aspirin use and HCC risk was assessed with a restricted cubic spline model. RESULTS Twenty-two studies were included in the meta-analysis. Aspirin use was associated with a reduced risk of HCC (HR=0.64, 95% CI: 0.56-0.75). The effect was robust across sex and age; however, women and the non-elderly had the greatest benefit from aspirin use. The preventive effect was well reproduced in those with comorbidities. Daily use and long-term use of aspirin appeared to offer greater benefits. Aspirin 100 mg/d was associated with maximum reduction of HCC risk. Aspirin use did slightly increase the risk of bleeding (HR=1.14, 95% CI: 1.02-1.27). CONCLUSIONS Our meta-analysis confirmed that use of aspirin significantly reduced the incident risk of HCC. Regular and long-term aspirin use offers a greater advantage. Aspirin use was associated with an increased risk of bleeding. We recommend 100 mg/d aspirin as a feasible dose for further research on primary prevention of HCC in a broad at-risk population.
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Affiliation(s)
- Lun-Jie Yan
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Sheng-Yu Yao
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Hai-Chao Li
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Guang-Xiao Meng
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Kai-Xuan Liu
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Zi-Niu Ding
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Jian-Guo Hong
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Zhi-Qiang Chen
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Zhao-Ru Dong
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Tao Li
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
- Department of Hepatobiliary Surgery, The second Hospital of Shandong University, Jinan, Shandong, China
- Correspondence to: Tao Li, Department of General Surgery, Qilu Hospital, Shandong University 107 West Wen Hua Road, Jinan, Shandong 250012, China. ORCID: https://orcid.org/0000-0002-5108-1774. Tel/Fax: +86-531-82166341, E-mail: mailto:
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13
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Park HJ, Kim SY, Singal AG, Lee SJ, Won HJ, Byun JH, Choi SH, Yokoo T, Kim MJ, Lim YS. Abbreviated magnetic resonance imaging vs ultrasound for surveillance of hepatocellular carcinoma in high-risk patients. Liver Int 2022; 42:2080-2092. [PMID: 34817921 DOI: 10.1111/liv.15110] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Revised: 09/30/2021] [Accepted: 11/20/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS We aimed to compare the performance of gadoxetic acid-enhanced abbreviated MRI (AMRI)-based surveillance and ultrasound-only surveillance in high-risk patients for hepatocellular carcinoma (HCC). METHODS Prospectively recruited high-risk patients (>5% annual risk of HCC) who underwent one to three rounds of complete gadoxetic acid-enhanced MRI (CMRI) and ultrasound at 6-months intervals were retrospectively analysed. AMRI consisted of diffusion-weighted, T2-weighted, and hepatobiliary phase imaging. The sensitivity, specificity, and accuracy of CMRI followed by AMRI (CAA), AMRI-only (AAA), and ultrasound-only (US) were compared using generalized estimating equations. Image quality was assessed. RESULTS In 382 patients, HCC was diagnosed in 43 (11.3%), including 42 with early-stage HCCs. The sensitivities of CAA (90.7%, 39/43) and AAA (86.0%, 37/43) were higher than US (27.9% [12/43]; P < 0.001), whereas the sensitivities of the two MRI approaches did not significantly differ (P = 0.56). The specificity of CAA (97.1%, 983/1012) was higher than AAA (95.6% [967/1012]; P = 0.01) and not significantly different from US (96.3% [975/1012]; P = 0.59). The CAA approach had the best accuracy of 96.9% (1022/1055), higher than the AAA approach (95.2% [1004/1055]; P = 0.01) and the US approach (93.6% [987/1055]; P = 0.01). Image quality was inadequate in 33.7% (356/1055) of US examinations but in only 10.0% (105/1055) of the AAA and 11.1% (117/1055) of the CAA approach. CONCLUSIONS In high-risk patients, AMRI-based surveillance approaches had higher sensitivities than ultrasound-only surveillance for early-stage HCC. A sequential MRI approach of CMRI followed by AMRIs showed superior accuracy than the AMRI-only or ultrasound-only approach.
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Affiliation(s)
- Hyo Jung Park
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - So Yeon Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.,Liver Cancer Center, Asan Medical Center, Seoul, Republic of Korea
| | - Amit G Singal
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - So Jung Lee
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.,Liver Cancer Center, Asan Medical Center, Seoul, Republic of Korea
| | - Hyung Jin Won
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.,Liver Cancer Center, Asan Medical Center, Seoul, Republic of Korea
| | - Jae Ho Byun
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.,Liver Cancer Center, Asan Medical Center, Seoul, Republic of Korea
| | - Sang Hyun Choi
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.,Liver Cancer Center, Asan Medical Center, Seoul, Republic of Korea
| | - Takeshi Yokoo
- Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Min-Ju Kim
- Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Young-Suk Lim
- Liver Cancer Center, Asan Medical Center, Seoul, Republic of Korea.,Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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14
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Kim BJ, Choi SH, Kim SY, Lim YS, Lee SJ, Byun JH, Won HJ. Liver Imaging Reporting and Data System categories: Long-term imaging outcomes in a prospective surveillance cohort. Liver Int 2022; 42:1648-1657. [PMID: 35445513 DOI: 10.1111/liv.15276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 04/17/2022] [Accepted: 04/19/2022] [Indexed: 02/13/2023]
Abstract
BACKGROUND AND AIMS We assessed the imaging outcomes of Liver Imaging Reporting and Data System (LI-RADS) v2018 categories in prospective hepatocellular carcinoma (HCC) surveillance cohort and determined imaging features significantly predictive of progression to a malignant LI-RADS category. METHODS The imaging outcomes of 120 patients (162 observations) prospectively enrolled between November 2011 and August 2012 were analysed according to LI-RADS v2018. Cumulative incidences for progression to a malignant category (LR-5 or LR-M) and LR-4 or higher were calculated for each baseline category and compared using log-rank tests. Clinical variables and imaging features significantly predictive of progression to a malignant category were evaluated using Cox proportional hazards modelling. RESULTS The 162 observations were initially categorized into 60 LR-2, 75 LR-3 and 27 LR-4. For LR-4 observations, the 1-year, 3-year and 5-year cumulative incidences of progression to a malignant category were 18.5% (95% confidence interval, 6.6-35.2%), 43.0% (23.1-61.5%) and 52.5% (25.9-73.5%), which were significantly higher than those of LR-2 and LR-3 (p < .001). For LR-3, the 1-year, 3-year and 5-year cumulative incidences of progression to LR-4 or higher were 4.1% (1.1-10.4%), 13.9% (6.7-23.6%) and 23.1% (12.7-35.4%), which were significantly higher than that of LR-2 (p = .009). In multivariable analysis, size ≥1.0 cm (hazard ratio [HR] = 2.58, 1.04-6.40) and nonrim arterial-phase hyperenhancement (HR = 2.45, 1.11-5.42) were significantly independently associated with progression to a malignant category. CONCLUSION Long-term imaging outcomes differed significantly according to LI-RADS category. Size ≥1.0 cm and nonrim arterial-phase hyperenhancement were imaging features significantly predictive of progression to a malignant category.
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Affiliation(s)
- Byoung Je Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sang Hyun Choi
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - So Yeon Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Young-Suk Lim
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - So Jung Lee
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jae Ho Byun
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Hyung Jin Won
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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15
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Gamma-Glutamyltransferase Activity (GGT) Is a Long-Sought Biomarker of Redox Status in Blood Circulation: A Retrospective Clinical Study of 44 Types of Human Diseases. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:8494076. [PMID: 35707277 PMCID: PMC9192220 DOI: 10.1155/2022/8494076] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Accepted: 05/05/2022] [Indexed: 12/09/2022]
Abstract
Background and Aim. Redox equilibria are critical for life, but the biomarkers of redox status are currently unavailable. Gamma-glutamyltransferase (GGT) is an essential factor for modulating redox equilibrium through glutathione. In clinical practice, increased circulating GGT activity is used as a hepatobiliary disease biomarker. However, increased circulating GGT activities have also been observed in cancers, heart disease, diabetes, hyperuricemia, inflammation, renal insufficiency, and other diseases, explained by its role in maintaining redox equilibrium inside and outside cells. Previous studies on GGT were mainly limited to one type of disease at one time. In the current study, we systematically compared the GGT levels in 44 different human diseases to test if it could serve as a redox status biomarker in blood circulation. Methods. The clinical GGT data from 168,858 patients with 44 diseases and 132,357 healthy control in the clinical laboratory of our hospital over the past five years were retrieved. All data were analyzed with SPSS, RStudio V.1.3.1073, and python libraries 3.8. Results. Thirty-eight out of 44 diseases had significantly increased (
) circulating GGT activities, whereas gastric cancer, anemia, renal cyst, cervical cancer, preeclampsia, and knee-joint degenerative diseases had significantly decreased (
) GGT activities compared to the healthy control. ROC analyses showed that GGT was an excellent biomarker for liver cancer (
), pancreatitis (
), or hepatic encephalopathy (
). All pancreas-related diseases had more than 8-fold increases in GGT activity span than the healthy control, while pancreatic cancer had a 12-fold increase (1021 U/L vs. 82 U/L). The knee-joint degenerative disease had the lowest median and narrowest GGT activity range (63 U/L). Furthermore, most diseases’ lowest to highest GGT activities were beyond the healthy control in both directions. Conclusions. Thirty-eight out of 44 diseases were in overall oxidative states defined by the increased GGT median values. In contrast, knee-joint degenerative disease, gastric cancer, anemia, renal cyst, cervical cancer, and preeclampsia were in overall antioxidative states. Moreover, most diseases swing between oxidative and antioxidative states, evidenced by the increased lowest to highest GGT activity ranges than the healthy control. Liver- and pancreas-related abnormalities were responsible for significantly increased GGT activities. Our overall results suggested that circulating GGT was a redox status biomarker.
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Chen PK, Chiu SH, Tsai MT, Chang KH, Chang WC, Lin HH, Lo CH, Huang GS, Chang PY. Combination therapy of sorafenib and drug-eluting bead transarterial chemoembolization for advanced hepatocellular carcinoma with and without hepatic arteriovenous shunt. J Chin Med Assoc 2022; 85:491-499. [PMID: 35152226 DOI: 10.1097/jcma.0000000000000696] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND To compare the efficacy and safety of combination therapy with sorafenib and drug-eluting bead transarterial chemoembolization (DEB-TACE) in advanced hepatocellular carcinoma (HCC) with or without hepatic arteriovenous shunt (HAVS). METHODS This retrospective, single-center study enrolled 59 advanced HCC patients treated with combination therapy, of whom 33 (55.9%) patients had HAVS. Tumor response according to the mRECIST criteria was evaluated based on the CT images 1 month after TACE, and changes in the arterial enhancement ratio (AER) of tumors and portal vein tumor thrombosis were also documented. Time-to-progression (TTP), overall survival (OS), and prognostic factors were analyzed. Safety was evaluated with the incidence of TACE-related complications within 6 weeks after TACE. RESULTS The tumor response between the two groups showed no significant difference in the objective response rate (69.2% in the group without HAVS vs 60.6% in the group with HAVS, p = 0.492) or disease control rate (92.3% vs 87.9%, p = 0.685). The two groups showed comparable TTP (4.23 vs 2.33 months, p = 0.235) and OS (12.77 vs 12.97 months, p = 0.910). A drop in the AER of tumors of more than 20% on post-TACE CT independently predicted better OS. With regard to safety, there was no significant difference between the two groups. CONCLUSION For advanced HCC, combination therapy had equal efficacy and safety in patients with HAVS compared to those without HAVS, indicating that DEB-TACE is an optional and effective treatment in these patients.
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Affiliation(s)
- Pin-Ko Chen
- Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, ROC, Taiwan
| | - Sung-Hua Chiu
- Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, ROC, Taiwan
| | - Ming-Ting Tsai
- Department of Medical Imaging, China Medical University Hsinchu Hospital, Hsinchu,Taiwan, ROC
| | - Kai-Hsiang Chang
- Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, ROC, Taiwan
| | - Wei-Chou Chang
- Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, ROC, Taiwan
| | - Hsuan-Hwai Lin
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC
| | - Cheng-Hsiang Lo
- Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC
| | - Guo-Shu Huang
- Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, ROC, Taiwan
| | - Ping-Ying Chang
- Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, ROC, Taiwan
- Department of Medical Imaging, China Medical University Hsinchu Hospital, Hsinchu,Taiwan, ROC
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC
- Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC
- Division of Hematology/Oncology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC
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17
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Ah Hwang J, Wook Kang T, Hye Min J, Kon Kim Y, Hyun Kim S, Hyun Sinn D, Kim K. Association between intensity of imaging surveillance and clinical outcomes in patients with hepatocellular carcinoma. Eur J Radiol 2022; 151:110328. [DOI: 10.1016/j.ejrad.2022.110328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 04/10/2022] [Accepted: 04/16/2022] [Indexed: 11/15/2022]
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Zhang L, Zhao Y, Guan H, Zhang D. HnRNPU-AS1 inhibits the proliferation, migration and invasion of HCC cells and induces autophagy through miR-556-3p/ miR-580-3p/SOCS6 axis. Cancer Biomark 2022; 34:443-457. [PMID: 35275521 DOI: 10.3233/cbm-210261] [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] [Indexed: 11/15/2022]
Abstract
BACKGROUND Long non-coding RNAs have drawn increasing research interest in cancer biology. This study aims to investigate the function roles and the underlying mechanism of HnRNPU-AS1 in Hepatocellular carcinoma (HCC). METHODS qRT-PCR was performed to detect the expression levels of HnRNPU-AS1, miR-556-3p, miR-580-3p in HCC tissues and cell lines. Western blot was used to determine protein levels of LC3-II, LC3-I, Beclin-1, P62, and SOCS6. Functional assays including CCK8 assay, colony formation assay, wound healing assay, Transwell assay were performed to evaluate the role of HnRNPU-AS1 in regulating the malignant phenotype of HCC cells. Dual luciferase reporter assay and RNA pull-down experiment were used to examined the RNA-RNA interaction. RESULTS HnRNPU-AS1 expression was decreased in HCC tissues and cell lines, which was associated with poor prognosis in HCC patients. Overexpression of HnRNPU-AS1 could inhibit the proliferation, migration, invasion but promote autophagy in HCC cells. Two miRNAs (miR-556-3p and miR-580-3p) were identified as potential targets of HnRNPU-AS1 in lncBASE database, which were significantly upregulated in HCC tissues and cell lines. Cell experiments demonstrated the effects of HnRNPU-AS1 overexpression could be attenuated by miR-556-3p or miR-580-3p overexpression. We further revealed that SOX6 was the downstream target of HnRNPU-AS1/miR-556-3p or miR-580-3p axis. Xenograft mouse model validated the tumor-suppressor role of HnRNPU-AS1 overexpression in vivo. CONCLUSIONS This study demonstrated the tumor suppressor function of HnRNPU-AS1 in HCC and identified the downstream molecules underlying its tumor suppressor function. Our results suggest that HnRNPU-AS1 suppresses HCC by targeting miR-556-3p and miR-580-3p/SOXS6 axis.
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19
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Park HJ, Lee TY, Kim SY, Kim MJ, Singal AG, Lee SJ, Won HJ, Byun JH, Lim YS. Hypervascular transformation of hepatobiliary phase hypointense nodules without arterial phase hyperenhancement on gadoxetic acid-enhanced MRI: long-term follow-up in a surveillance cohort. Eur Radiol 2022; 32:5064-5074. [PMID: 35229195 DOI: 10.1007/s00330-022-08623-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 01/25/2022] [Accepted: 01/31/2022] [Indexed: 11/27/2022]
Abstract
OBJECTIVES With the increasing use of gadoxetic acid-enhanced MRI for HCC surveillance, hepatobiliary phase (HBP) hypointense nodules without arterial phase hyperenhancement (APHE) are frequently encountered. We investigated the rate of these nodules with hypervascular transformation, which suggests hepatocarcinogenesis, by using a prospectively collected longitudinal surveillance cohort data. METHODS This study included 382 prospectively enrolled patients at high risk for developing HCC who underwent 1-3 rounds of bi-annual surveillance gadoxetic acid-enhanced MRI. MRI was analyzed to detect HBP hypointense nodules without APHE. Follow-up dynamic CTs and MRIs were evaluated to detect hypervascular transformation of the nodules. Cox proportional hazards regression analyses were used to find predictors for hypervascular transformation. RESULTS A total of 76 HBP hypointense nodules without APHE were found in 48 patients, giving a prevalence of 12.6% (48/382). The mean nodule size was 10.8 mm, with 43.4% (33/76) being ≥ 10 mm. Over a median follow-up of 78.6 months, 19 nodules (25.0%) showed hypervascular transformation, all of which demonstrated typical imaging features of HCC. On multivariable Cox-regression analysis, size (≥ 10 mm) was the only independent predictor of hypervascular transformation (hazard ratio, 3.31; 95% confidence interval, 1.21-9.05). The cumulative incidence of hypervascular transformation at 12 and 60 months of nodules ≥ 10 mm was 12.3% and 50.4%, respectively, while that of nodules < 10 mm was 2.5% and 13.9%, respectively. CONCLUSIONS About half of the HBP hypointense nodules ≥ 10 mm without APHE transformed to HCC at 5 years of follow-up, indicating the necessity for cautious monitoring with an augmented and extended follow-up schedule for these nodules. KEY POINTS • The prevalence of HBP hypointense nodules without APHE was 12.6% in a prospectively recruited population at high risk of developing HCC. • Nodule size ≥ 10 mm was significantly associated with hypervascular transformation, and approximately half of the HBP hypointense nodules ≥ 10 mm without APHE transformed to HCC during 5 years of follow-up. • Given the risk of malignant transformation, HBP hypointense nodules ≥ 10 mm without APHE should be closely monitored.
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Affiliation(s)
- Hyo Jung Park
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Tae Young Lee
- Department of Radiology, Ulsan University Hospital, Ulsan, Republic of Korea
| | - So Yeon Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea. .,Liver Cancer Center, Asan Medical Center, Seoul, Republic of Korea.
| | - Min-Ju Kim
- Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Amit G Singal
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - So Jung Lee
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.,Liver Cancer Center, Asan Medical Center, Seoul, Republic of Korea
| | - Hyung Jin Won
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.,Liver Cancer Center, Asan Medical Center, Seoul, Republic of Korea
| | - Jae Ho Byun
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.,Liver Cancer Center, Asan Medical Center, Seoul, Republic of Korea
| | - Young-Suk Lim
- Liver Cancer Center, Asan Medical Center, Seoul, Republic of Korea.,Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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20
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Prasad U, Kumar D, Bharti RR, Suman SK, Singh A, Kumar R. Typical and Atypical Imaging Findings of Hepatocellular Carcinoma on Multiphasic MDCT Scan in Histologically Proved Cases. JOURNAL OF GASTROINTESTINAL AND ABDOMINAL RADIOLOGY 2022. [DOI: 10.1055/s-0042-1742771] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
Abstract
Abstract
Objective The purpose of this study was to find out the incidence of typical and atypical radiological imaging findings of hepatocellular carcinoma (HCC) on multiphase multidetector computed tomography (MDCT) scans in histologically proven cases.
Materials and Methods A multiphase computed tomography study of 73 patients with histologically proven HCC was evaluated by a radiologist. Our multiphasic protocol was composed of precontrast, arterial, portal, and delayed venous phases. The reviewers analyzed the CT images for tumor size, enhancement patterns of HCC in different phases, relative timing of washout, internal cystic changes, and presence of dysmorphic intratumoral vessel aneurysms or arteriovenous shunt.
Results Most of the cases (95.9%) showed typical enhancement patterns in MDCT, i.e., enhancements in the arterial phase with the portal or delayed venous phase contrast washout. Three cases (4.9%) out of 73 HCC showed enhancements in the portal phase and washout in the delayed venous phase. Seven cases out of total 73 HCC (9.5%) patients showed heterogeneous enhancements in both arterial and portal phases and contrast washout in the delayed venous phase. Venous thrombosis was noted in about 44 cases (60%) out of total 73 patients, in which portal vein thrombosis was more common than hepatic veins/inferior vena cava.
Conclusion Most of the HCC show typical enhancement patterns, i.e., heterogeneous enhancements in the arterial phase and washout in the portal venous phase when we use MDCT. These findings are higher than those described previously. However, in our study, the main difference with MDCT was lower frequency of intratumoral pseudoaneurysm and bile duct invasion, and intratumoral fat and calcification (atypical character of HCC) were not found which were rare findings in previous study.
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Affiliation(s)
- Umakant Prasad
- Department of Radiodiagnosis, Indira Gandhi Institute of Medical Science, Patna, Bihar, India
| | - Deepak Kumar
- Department of Radiodiagnosis, Indira Gandhi Institute of Medical Science, Patna, Bihar, India
| | - Rashmi Rani Bharti
- Department of Pathology, Indira Gandhi Institute of Medical Science, Patna, Bihar
| | - Sanjay Kumar Suman
- Department of Radiodiagnosis, Indira Gandhi Institute of Medical Science, Patna, Bihar, India
| | - Aishwerya Singh
- Department of Radiodiagnosis, Indira Gandhi Institute of Medical Science, Patna, Bihar, India
| | - Ravikant Kumar
- Department of Gastroentrology, Indira Gandhi Institute of Medical Science, Patna, India
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21
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Yang H, Wang L, Zheng Y, Hu G, Ma H, Shen L. Knockdown of zinc finger protein 267 suppresses diffuse large B-cell lymphoma progression, metastasis, and cancer stem cell properties. Bioengineered 2022; 13:1686-1701. [PMID: 35001816 PMCID: PMC8805851 DOI: 10.1080/21655979.2021.2014644] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Accepted: 11/20/2021] [Indexed: 12/12/2022] Open
Abstract
Zinc finger protein 267 (ZNF267) is a member of the Kruppel-like transcription factor family, which regulates various biological processes such as cell proliferation and differentiation. However, the biological significance of ZNF267 and its potential role in diffuse large B-cell lymphoma (DLBCL) remain to be documented. Experiments were herein conducted to study the role of ZNF267 in DLBCL. real-time quantitative reverse transcription PCR and Western blotting assays were conducted to detect the expression of ZNF267 in tissues and cells. Tissue microarray and bioinformatics analyses of public data were also done to detect the expression status and clinical significance of ZNF267. Functional cell experiments including CCK8 assay, colony formation assay, 5-ethynyl-2'-deoxyuridine (EDU) assay, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) assay, transwell assay, and wound healing assay were conducted to study the effects of ZNF267 knockdown and overexpression on cell proliferation and mobility. Xenograft assay was also conducted to confirm the effects of ZNF267 knockdown in vivo. In the present study, we found ZNF267 was significantly upregulated in DLBCL and predicted a poor survival outcome based on the bioinformatics analysis. Functionally, the knockdown of ZNF267 resulted in less cell proliferation and mobility, whereas the overexpression led to enhanced cell proliferation and mobility. Animal experiments also confirmed that ZNF267 silence contributed to less tumor growth and less lung metastasis. Further analysis showed that ZFN267 knockdown resulted in decreased epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) properties. Our results suggest that ZNF267 is an oncogene in DLBCL and its silence could compromise the aggression of DLBCL, which makes ZNF267 a promising therapeutic target.
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Affiliation(s)
- Hua Yang
- Department of Hematology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Linmei Wang
- Department of Resoiratory and Critical Care Medicine, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yingbin Zheng
- Department of General Surgery, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Guiming Hu
- Department of Pathology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Hongyan Ma
- Department of Hematology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Liyun Shen
- Department of Hematology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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22
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Park HJ, Seo N, Kim SY. Current Landscape and Future Perspectives of Abbreviated MRI for Hepatocellular Carcinoma Surveillance. Korean J Radiol 2022; 23:598-614. [PMID: 35434979 PMCID: PMC9174497 DOI: 10.3348/kjr.2021.0896] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 01/18/2022] [Accepted: 02/10/2022] [Indexed: 11/15/2022] Open
Abstract
While ultrasound (US) is considered an important tool for hepatocellular carcinoma (HCC) surveillance, it has limited sensitivity for detecting early-stage HCC. Abbreviated MRI (AMRI) has recently gained popularity owing to better sensitivity in its detection of early-stage HCC than US, while also minimizing the time and cost in comparison to complete contrast-enhanced MRI, as AMRI includes only a few essential sequences tailored for detecting HCC. Currently, three AMRI protocols exist, namely gadoxetic acid-enhanced hepatobiliary-phase AMRI, dynamic contrast-enhanced AMRI, and non-enhanced AMRI. In this study, we discussed the rationale and technical details of AMRI techniques for achieving optimal surveillance performance. The strengths, weaknesses, and current issues of each AMRI protocol were also elucidated. Moreover, we scrutinized previously performed AMRI studies regarding clinical and technical factors. Reporting and recall strategies were discussed while considering the differences in AMRI protocols. A risk-stratified approach for the target population should be taken to maximize the benefits of AMRI and the cost-effectiveness should be considered. In the era of multiple HCC surveillance tools, patients need to be fully informed about their choices for better adherence to a surveillance program.
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Affiliation(s)
- Hyo Jung Park
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Nieun Seo
- Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - So Yeon Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
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23
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Impact of Alcohol Abstinence on the Risk of Hepatocellular Carcinoma in Patients With Alcohol-Related Liver Cirrhosis. Am J Gastroenterol 2021; 116:2390-2398. [PMID: 34569986 DOI: 10.14309/ajg.0000000000001399] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Accepted: 07/15/2021] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Although alcohol cessation is the only effective treatment for alcohol-related liver disease, few data exist concerning its influence on the risk of hepatocellular carcinoma (HCC). We aimed to evaluate the effect of alcohol abstinence on the incidence of HCC in patients with alcohol-related cirrhosis. METHODS We studied 727 patients with alcohol-related cirrhosis (247 with compensated disease and 480 with previous decompensation) who were included in a surveillance program for the early detection of HCC and prospectively followed. Baseline clinical and biological parameters and alcohol consumption during follow-up were recorded. Abstinence was defined as the absence of any alcohol use. RESULTS During follow-up (median 54 months), 354 patients (48.7%) remained abstinent and 104 developed HCC (2.3 per 100 person-years). Factors independently associated with the risk of HCC among patients with previous decompensation were age, male gender, and aspartate aminotransferase, whereas abstinence was not linked to a reduced risk (hazard ratio 0.95; 95% confidence interval 0.59-1.52). However, among patients without previous decompensation, prothrombin activity and abstinence were independently associated with the risk of HCC. Abstinent patients had a significant decrease in the risk of developing tumor (hazard ratio 0.35; 95% confidence interval 0.13-0.94). These results did not change after applying a competing risk analysis where death and liver transplantation were considered as competing events. DISCUSSION Alcohol abstinence reduced the risk of HCC in patients with alcohol-related cirrhosis, but only in those without a history of decompensated disease. This finding emphasizes the need for an early diagnosis of alcohol-related liver disease and for implementing strategies leading to an increase in the rate of achieving and maintaining abstinence among this population.
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Effectiveness of combined therapy radiofrequency ablation/transarterial chemoembolization versus transarterial chemoembolization/radiofrequency ablation on management of hepatocellular carcinoma. Eur J Gastroenterol Hepatol 2021; 33:1573-1577. [PMID: 32796363 DOI: 10.1097/meg.0000000000001878] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND One of the most widespread cancer-associated death worldwide is Hepatocellular carcinoma. Concerning hepatic malignant tumor staging system known as Barcelona clinic of liver cancer, a superior curative response could be carried out by combined techniques [radiofrequency ablation (RFA) and transarterial chemoembolization (TACE)] for stage B comparing with TACE alone as palliative monotherapy. OBJECTIVES To discuss the merging effect of RFA followed by TACE and vice versa on objective response, overall survival, local recurrence and tumor-free survival. PATIENTS AND METHODS Sixty-eight cases included with hepatic tumor on top of chronic liver disease post-viral infection and divided into two groups according to different combined treatment modality; first cohort included 34 patients treated with TACE followed by RFA, while the second one included 34 patients treated with RFA followed by TACE for two lesions or single medium-sized lesion stage. RESULTS Complete response and objective response rates were 91% and 82% after TACE/RFA and 100% and 91% after RFA/TACE, respectively. Regarding Milan criteria, there was significant downstaging after RFA/TACE (P < 0.05). First and second overall survival rates were 85% and 65% after TACE/RFA versus 100% and 74%, respectively, after RFA/TACE (P > 0.05). Kaplan-Meier curve as regards disease-free survival rate, median time were 17.1 months [95% confidence interval (CI) 12.2-22.0] in TACE/RFA and 23.2 (95% CI 18.1-28.2) months in RFA/TACE (P > 0.05). CONCLUSION RFA/TACE showed effective complete response, downstaging, disease-free survival and overall survival for the treatment of hepatic malignant tumors.
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Hwang SH, Hong SB, Han K, Seo N, Choi JY, Lee JH, Park S, Lim YS, Kim DY, Kim SY, Park MS. A New Reporting System for Diagnosis of Hepatocellular Carcinoma in Chronic Hepatitis B With Clinical and Gadoxetic Acid-Enhanced MRI Features. J Magn Reson Imaging 2021; 55:1877-1886. [PMID: 34668595 DOI: 10.1002/jmri.27962] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Revised: 10/04/2021] [Accepted: 10/08/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Current major guidelines for diagnosis of hepatocellular carcinoma (HCC) based on imaging findings are different from each other and do not include clinical risk factors as a diagnostic criteria. PURPOSE To developed and validated a new diagnostic score system using MRI and clinical features as applied in chronic hepatitis B patients. STUDY TYPE Retrospective observational study. SUBJECT A total of 418 treatment-naïve patients (out of 902 patients) with chronic hepatitis B having 556 lesions suspected for HCC which were eligible for curative treatment. FIELD STRENGTH/SEQUENCE T1W GRE in- and opposed-phase, T2W FSE, DWI, and T1W 3D-GRE dynamic contrast-enhanced sequences at 1.5 T and 3 T. ASSESSMENT Six radiologists with 7-22 years of experience independently evaluated MR images based on Liver Imaging Reporting and Data System (LI-RADS) version 2018. STATISTICAL TESTS Based on logistic regression analysis of MRI features and clinical factors, a risk score system was devised in derivation cohorts (268 patients, 352 lesions) and externally validated (150 patients, 204 lesions). The performance of the new score system was assessed by Harell's c-index. Using cutoff value of 12, maintaining positive predictive value ≥95%, the diagnostic performances of the score system were compared with those of LR-5. RESULTS The 15-point diagnostic scoring system used MRI features (lesion size, nonrim arterial phase hyperenhancement, portal venous phase hypointensity, hepatobiliary phase hypointensity, and diffusion restriction) and clinical factors (alpha-fetoprotein and platelet). It showed good discrimination in the derivation (c-index, 0.946) and validation cohorts (c-index, 0.907). Using a risk score of 12 as a cut-off, this system yielded higher sensitivity than LR-5 (derivation cohort, 76.8% vs. 52.1%; validation cohort, 73.4% vs. 49.5%) without significant decrease in specificity (derivation cohort, 93.1% vs. 97.2%, P = 0.074; validation cohort, 91.7% vs. 96.1%, P = 0.299). DATA CONCLUSION A new score system showed improved sensitivity in chronic hepatitis B patients compared to LI-RADS without significant compromise in specificity. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.
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Affiliation(s)
- Shin Hye Hwang
- Department of Radiology, Yongin Severance Hospital, Yongin, Gyeonggi-do, South Korea
| | - Seung Baek Hong
- Department of Radiology, Biomedical Research Institute, Pusan National University Hospital, and Pusan National University School of Medicine, Pusan, South Korea.,Department of Radiology, Asan Medical Center, Ulsan University College of Medicine, Seoul, South Korea
| | - Kyunghwa Han
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Nieun Seo
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Jin-Young Choi
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Jei Hee Lee
- Department of Radiology, Ajou University Hospital, Suwon, South Korea
| | - Sumi Park
- Department of Radiology, National Health Insurance Service Ilsan Hospital, Goyang, South Korea
| | - Young-Suk Lim
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Do Young Kim
- Department of Internal Medicine, Severance Hospital, Seoul, South Korea
| | - So Yeon Kim
- Department of Radiology, Asan Medical Center, Ulsan University College of Medicine, Seoul, South Korea
| | - Mi-Suk Park
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
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Pearson MM, Kim NJ, Berry K, Moon AM, Su F, Vutien P, Green PK, Williams EC, Ioannou GN. Associations Between Alcohol Use and Liver-Related Outcomes in a Large National Cohort of Patients With Cirrhosis. Hepatol Commun 2021; 5:2080-2095. [PMID: 34601829 PMCID: PMC8631097 DOI: 10.1002/hep4.1776] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Revised: 05/10/2021] [Accepted: 06/13/2021] [Indexed: 11/11/2022] Open
Abstract
Alcohol use can cause hepatic necroinflammation and worsening portal hypertension in patients with cirrhosis. We aimed to evaluate the associations between degree of alcohol use and clinical liver‐related outcomes according to etiology of cirrhosis. In this retrospective cohort analysis, 44,349 U.S. veterans with cirrhosis from alcohol‐associated liver disease (ALD), chronic hepatitis C virus (HCV) infection, or nonalcoholic fatty liver disease were identified who completed the Alcohol Use Disorders Identification Test Consumption questionnaire in 2012. Based on this score, level of alcohol use was categorized as none, low level, or unhealthy. Multivariable Cox proportional hazards regression was used to assess for associations between alcohol use and mortality, cirrhosis decompensation (new ascites, encephalopathy, or variceal bleeding), and hepatocellular carcinoma (HCC). At baseline, 36.4% of patients endorsed alcohol use and 17.1% had unhealthy alcohol use. During a mean 4.9 years of follow‐up, 25,806 (57.9%) patients died, 9,409 (21.4%) developed a new decompensation, and 4,733 (11.1%) developed HCC. In patients with ALD‐cirrhosis and HCV‐cirrhosis, unhealthy alcohol use, compared with no alcohol use, was associated with higher risks of mortality (adjusted hazard ratio [aHR] = 1.13, 95% confidence interval [CI] = 1.07‐1.19 and aHR = 1.14, 95% CI = 1.08‐1.20, respectively) and decompensation (aHR = 1.18, 95% CI = 1.07‐1.30 and aHR = 1.08, 95% CI = 1.00‐1.16, respectively). Alcohol use was not associated with HCC, regardless of cirrhosis etiology. Conclusion: Unhealthy alcohol use was common in patients with cirrhosis and was associated with higher risks of mortality and cirrhosis decompensation in patients with HCV‐cirrhosis and ALD‐cirrhosis. Therefore, health care providers should make every effort to help patients achieve abstinence. The lack of association between alcohol use and HCC merits further investigation.
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Affiliation(s)
- Meredith M Pearson
- Division of Gastroenterology and Hepatology, University of Washington, Seattle, WA, USA
| | - Nicole J Kim
- Division of Gastroenterology and Hepatology, University of Washington, Seattle, WA, USA
| | - Kristin Berry
- Health Service Research and Development, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA
| | - Andrew M Moon
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, USA
| | - Feng Su
- Division of Gastroenterology and Hepatology, University of Washington, Seattle, WA, USA
| | - Philip Vutien
- Division of Gastroenterology and Hepatology, University of Washington, Seattle, WA, USA
| | - Pamela K Green
- Health Service Research and Development, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA
| | - Emily C Williams
- Health Service Research and Development, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA.,Department of Health Services, University of Washington, Seattle, WA, USA
| | - George N Ioannou
- Division of Gastroenterology and Hepatology, University of Washington, Seattle, WA, USA.,Division of Gastroenterology, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA
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27
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Yan LJ, Yao SY, Meng GX, Liu KX, Li HC, Ding ZN, Dong ZR, Hong JG, Chen ZQ, Li T. Sex and regional disparities in incidence of hepatocellular carcinoma in autoimmune hepatitis: a systematic review and meta-analysis. Hepatol Int 2021; 15:1413-1420. [PMID: 34478116 DOI: 10.1007/s12072-021-10249-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Accepted: 08/19/2021] [Indexed: 11/29/2022]
Abstract
BACKGROUND Recent studies have identified an increased risk of hepatocellular carcinoma (HCC) in autoimmune hepatitis (AIH). Sex and regional disparities in incidence of HCC in AIH continue to be reported worldwide. Nevertheless, the magnitude of this gap remains unknown. METHOD We searched several databases including PubMed, Embase, Web of Science, Cochrane Library, Wanfang Data, CNKI and SinoMed. Incidence rates of HCC in AIH were combined and analyzed following the EBayes method. Incidence rate ratios were pooled to assess the sex differences. The impact of population difference, sex, age, cirrhotic condition was further analyzed with subgroup analysis and linear regression analysis. RESULT 39 studies meeting our eligibility criteria were chosen for the analysis. The pooled incidence rate of HCC in AIH was 3.54 per 1000 person years (95% CI 2.76-4.55). Pooled IRR for the risk of HCC in male AIH patients compared to female was 2.16 (95% CI 1.25-3.75), with mild heterogeneity among studies. The pooled HCC incidence rate in AIH by continents was as follows: Europe 2.37 per 1000 person-years (95% CI 1.45-3.88), Asia 6.18 per 1000 person-years (95%CI 5.51-6.93), North America 2.97 per 1000 person-years (95%CI 2.40-3.68), Oceania 2.60 (95%CI 0.54-7.58). The pooled HCC incidence rate in AIH-related cirrhosis by continent was as follows: Europe 6.35 per 1000 person-years (95%CI 3.94-10.22), Asia 17.02 per 1000 person-years (95%CI 11.18-25.91), North America 10.89 per 1000 person-years (95%CI 6.69-17.74). CONCLUSION A higher HCC incidence in AIH was observed among male and in Asian populations. Cirrhosis status at AIH diagnosis is significantly associated with an increased incidence rate for HCC, and routine HCC surveillance is recommended for patients with AIH cirrhosis, especially for those in Asia.
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Affiliation(s)
- Lun-Jie Yan
- Department of General Surgery, Qilu Hospital, Shandong University, 107 West Wen Hua Road, Jinan, 250012, People's Republic of China
| | - Sheng-Yu Yao
- Department of General Surgery, Qilu Hospital, Shandong University, 107 West Wen Hua Road, Jinan, 250012, People's Republic of China
| | - Guang-Xiao Meng
- Department of General Surgery, Qilu Hospital, Shandong University, 107 West Wen Hua Road, Jinan, 250012, People's Republic of China
| | - Kai-Xuan Liu
- Department of General Surgery, Qilu Hospital, Shandong University, 107 West Wen Hua Road, Jinan, 250012, People's Republic of China
| | - Hai-Chao Li
- Department of General Surgery, Qilu Hospital, Shandong University, 107 West Wen Hua Road, Jinan, 250012, People's Republic of China
| | - Zi-Niu Ding
- Department of General Surgery, Qilu Hospital, Shandong University, 107 West Wen Hua Road, Jinan, 250012, People's Republic of China
| | - Zhao-Ru Dong
- Department of General Surgery, Qilu Hospital, Shandong University, 107 West Wen Hua Road, Jinan, 250012, People's Republic of China
| | - Jian-Guo Hong
- Department of General Surgery, Qilu Hospital, Shandong University, 107 West Wen Hua Road, Jinan, 250012, People's Republic of China
| | - Zhi-Qiang Chen
- Department of General Surgery, Qilu Hospital, Shandong University, 107 West Wen Hua Road, Jinan, 250012, People's Republic of China
| | - Tao Li
- Department of General Surgery, Qilu Hospital, Shandong University, 107 West Wen Hua Road, Jinan, 250012, People's Republic of China. .,Department of Hepatobiliary Surgery, The Second Hospital of Shandong University, Jinan, 250012, People's Republic of China.
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28
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Honmyo N, Kobayashi T, Kuroda S, Ide K, Ohira M, Tahara H, Morimoto H, Tanimine N, Hamaoka M, Yamaguchi M, Yamamoto M, Takei D, Aikata H, Chayama K, Ohdan H. Risk Factors for Hepatocellular Carcinoma After Splenectomy in Liver Cirrhotic Patients. Am Surg 2021:31348211041562. [PMID: 34455865 DOI: 10.1177/00031348211041562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND Splenectomy is sometimes indicated for portal hypertension caused by cirrhosis, which is a risk for hepatic carcinogenesis. This study aimed to identify risk factors for hepatocellular carcinoma (HCC) development after splenectomy. METHODS This retrospective study included 65 patients who underwent splenectomy for portal hypertension between 2009 and 2017. Cox regression analyses were performed to identify factors related to HCC development after splenectomy. The predictive index for HCC development was constructed from the results of multivariate analysis, and 3 risk-dependent groups were defined. Discrimination among the groups was estimated using Kaplan-Meier curves and the log-rank test. RESULTS Post-splenectomy, 36.9% of patients developed HCC. In the univariate analysis, the etiology of cirrhosis (hepatitis C virus antibody, P = .005, and hepatitis B surface antigen, P = .008, referring to non-B and non-C patients, respectively), presence of HCC history (P < .001), and preoperative hemoglobin level (P = .007) were related to HCC development, and the presence of HCC history (P = .002) and preoperative hemoglobin level (P = .022) were independent risk factors. The predictive index classified three groups at risk; the hazards in each group were significantly different (low vs middle risk, P = .035, and middle vs high risk, P = .011). DISCUSSION The etiology of cirrhosis, presence of HCC history, and hemoglobin level were associated with HCC development after splenectomy. The predictive model may aid in HCC surveillance after splenectomy for patients with portal hypertension.
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Affiliation(s)
- Naruhiko Honmyo
- Department of Gastroenterological and Transplant Surgery, 12803Hiroshima University, Hiroshima, Japan
| | - Tsuyoshi Kobayashi
- Department of Gastroenterological and Transplant Surgery, 12803Hiroshima University, Hiroshima, Japan
| | - Shintaro Kuroda
- Department of Gastroenterological and Transplant Surgery, 12803Hiroshima University, Hiroshima, Japan
| | - Kentaro Ide
- Department of Gastroenterological and Transplant Surgery, 12803Hiroshima University, Hiroshima, Japan
| | - Masahiro Ohira
- Department of Gastroenterological and Transplant Surgery, 12803Hiroshima University, Hiroshima, Japan
| | - Hiroyuki Tahara
- Department of Gastroenterological and Transplant Surgery, 12803Hiroshima University, Hiroshima, Japan
| | - Hiroshi Morimoto
- Department of Gastroenterological and Transplant Surgery, 12803Hiroshima University, Hiroshima, Japan
| | - Naoki Tanimine
- Department of Gastroenterological and Transplant Surgery, 12803Hiroshima University, Hiroshima, Japan
| | - Michinori Hamaoka
- Department of Gastroenterological and Transplant Surgery, 12803Hiroshima University, Hiroshima, Japan
| | - Megumi Yamaguchi
- Department of Gastroenterological and Transplant Surgery, 12803Hiroshima University, Hiroshima, Japan
| | - Masateru Yamamoto
- Department of Gastroenterological and Transplant Surgery, 12803Hiroshima University, Hiroshima, Japan
| | - Daisuke Takei
- Department of Gastroenterological and Transplant Surgery, 12803Hiroshima University, Hiroshima, Japan
| | - Hiroshi Aikata
- Department of Gastroenterology and Metabolism, 12803Hiroshima University, Hiroshima, Japan.,Research Center for Hepatology and Gastroenterology, 12803Hiroshima University, Hiroshima, Japan
| | - Kazuaki Chayama
- Department of Gastroenterology and Metabolism, 12803Hiroshima University, Hiroshima, Japan.,Research Center for Hepatology and Gastroenterology, 12803Hiroshima University, Hiroshima, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, 12803Hiroshima University, Hiroshima, Japan
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Rodríguez-Escaja C, Á Navascués C, González-Diéguez L, Cadahía V, Varela M, de Jorge MÁ, Castaño-García A, Rodríguez M. Diabetes is not associated with an increased risk of hepatocellular carcinoma in patients with alcoholic or hepatitis C virus cirrhosis. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2021; 113:505-511. [PMID: 33244982 DOI: 10.17235/reed.2020.6953/2020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND AND AIMS diabetes has been reported as a risk factor for hepatocellular carcinoma (HCC) in population-based studies but there are controversial data in patients with cirrhosis. Metformin could have a protective role in HCC development. The aim of this study was to determine the influence of diabetes on the risk of developing HCC in patients with alcohol- and hepatitis C virus (HCV)-related cirrhosis. METHODS a cohort of 982 Caucasian patients were analyzed with alcoholic or HCV cirrhosis, included from 1992 to 2014 in a HCC surveillance program and prospectively followed. The influence of diabetes on the development of HCC was analyzed by Kaplan Meier analysis and adjusted with a Cox regression for relevant co-factors. RESULTS after a median follow-up of 49.5 (24.0-96.0) months, 156 patients (15.8 %) developed HCC. There were no differences in the cumulative incidences of HCC after 20 years between diabetic and non-diabetic patients in the global (53.5 % vs 45.4 %; p = 0.26), alcoholic (50.4 % vs 45.4 %; p = 0.21) or HCV (60 % vs 43.1 %; p = 0.57) cirrhosis series. Diabetes did not constitute a risk factor after adjusting for other potential co-factors, neither in the whole series (hazard ratio [HR]: 1.12, 95 % CI: 0.78-1.51; p = 0.26), alcoholic (HR: 1.160, 95 % CI: 0.74-1.82; p = 0.50) or HCV cirrhosis cohort (HR: 1.17, 95 % CI: 0.63-2.19; p = 0.60). These figures did not change after excluding patients treated with metformin. CONCLUSIONS in Caucasian patients with alcoholic or HCV cirrhosis, diabetes is not a risk factor for developing HCC. This lack of an association does not seem to be a consequence of the protective effect of metformin.
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Affiliation(s)
- Carlos Rodríguez-Escaja
- Liver Unit. Division of Gastroenterology and Hepat, Hospital Universitario Central de Asturias, España
| | - Carmen Á Navascués
- Liver Unit. Division of Gastroenterology and Hepat, Hospital Universitario Central de Asturias, España
| | - Luisa González-Diéguez
- Liver Unit. Division of Gastroenterology and Hepat, Hospital Universitario Central de Asturias, España
| | - Valle Cadahía
- Liver Unit. Division of Gastroenterology and Hepat, Hospital Universitario Central de Asturias, España
| | - María Varela
- Liver Unit. Division of Gastroenterology and Hepat, Hospital Universitario Central de Asturias, España
| | - Miguel Ángel de Jorge
- Liver Unit. Division of Gastroenterology and Hepat, Hospital Universitario Central de Asturias, España
| | - Andrés Castaño-García
- Liver Unit. Division of Gastroenterology and Hepat, Hospital Universitario Central de Asturias, España
| | - Manuel Rodríguez
- Liver Unit. Division of Gastroenterology and Hepat, Hospital Universitario Central de Asturias, España
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Risk Factors and Biomarkers for Chronic Hepatitis B Associated Hepatocellular Carcinoma. Int J Mol Sci 2021; 22:ijms22020479. [PMID: 33418899 PMCID: PMC7825109 DOI: 10.3390/ijms22020479] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Revised: 12/21/2020] [Accepted: 12/28/2020] [Indexed: 02/08/2023] Open
Abstract
Globally, hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) is one of the major causes of cancer-related mortality. This is, in part, due to delayed diagnosis and limited therapeutic options with more advanced stages of the disease. Given the prognostic importance of early diagnosis, novel methods for early detection are in need. Unlike most other cancer types, tissue is not required to diagnose HCC and is frequently avoided given the inherent risks of liver biopsy, so less invasive methods of obtaining tumor material are currently under investigation. Material shed from tumors into the periphery are being investigated for their potential to both surveil and diagnose patients for HCC. These materials include circulating tumor cells, DNA, RNA, and exosomes, and are collectively termed a “liquid biopsy”. In this review article, we discuss the evolving literature regarding the different risk factors for HCC and the types of emerging novel biomarkers that show promise in the prevention and early diagnosis of HCC within the context of HBV infection.
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31
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Sun T, Ren Y, Kan X, Chen L, Zhang W, Yang F, Zheng C. Advanced Hepatocellular Carcinoma With Hepatic Arterioportal Shunts: Combination Treatment of Transarterial Chemoembolization With Apatinib. Front Mol Biosci 2020; 7:607520. [PMID: 33344507 PMCID: PMC7746797 DOI: 10.3389/fmolb.2020.607520] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Accepted: 11/13/2020] [Indexed: 01/11/2023] Open
Abstract
Object: This study aimed to compare the efficacy and safety of transarterial chemoembolization (TACE) combining with apatinib (TACE-apatinib) and TACE-alone for patients with advanced hepatocellular carcinoma (HCC) with hepatic arterioportal shunts (APS). Materials and Methods: This retrospective study evaluated the medical records of patients with advanced HCC with APS who underwent TACE-apatinib or TACE-alone from June 2015 to January 2019. The occlusion of the shunt was performed during the TACE procedure. The time to tumor progression (TTP) and overall survival (OS) of study patients were evaluated. The modified Response Evaluation Criteria in solid tumors (mRECIST) was used to evaluate the treatment response. The apatinib-related adverse events were recorded. Results: Fifty-eight patients were included in this study. Twenty-seven patients underwent the treatment of TACE-apatinib, and 31 received TACE-alone treatment. The median overall survival (OS) and median time of tumor progression (TTP) in the TACE-apatinib group were significantly longer than those of the TACE-alone group (OS: 12.0 vs. 9.0 months, P = 0.000; TTP: 9.0 vs. 5.0 months, P = 0.041). Multivariate analysis revealed that TACE-apatinib was a protective factor for OS, and there was no independent risk factor for TTP. In the TACE-apatinib group, the grade 3 apatinib-related adverse events occurred in four patients. Conclusion: TACE-apatinib was an efficacious and safe treatment for patients with advanced HCC with APS, and apatinib improved the efficacy of TACE in the treatment of these patients.
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Affiliation(s)
- Tao Sun
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Yanqiao Ren
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Xuefeng Kan
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Lei Chen
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Weihua Zhang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Fan Yang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Chuansheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
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Investigation of the relationship between sensorineural hearing loss and associated comorbidities in patients with chronic kidney disease: A nationwide, population-based cohort study. PLoS One 2020; 15:e0238913. [PMID: 32915865 PMCID: PMC7485846 DOI: 10.1371/journal.pone.0238913] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2019] [Accepted: 08/26/2020] [Indexed: 02/07/2023] Open
Abstract
Hearing impairment was observed in patients with chronic kidney disease (CKD). Our purpose was to investigate the relationship between sensorineural hearing loss (SNHL) and associated comorbidities in the CKD population. We conducted a retrospective, population-based study to examine the risk of developing SNHL in patients with CKD. Population-based data from 2000–2010 from the Longitudinal Health Insurance Database of the Taiwan National Health Insurance Research Database was used in this study. The population sample comprised 185,430 patients who were diagnosed with CKD, and 556,290 without CKD to determine SNHL risk factors. Cox proportional hazard regression analysis demonstrated the CKD group had a significantly increased risk of SNHL compared with the non-CKD group [adjusted hazard ratio (HR), 3.42; 95% confidence interval (CI), 3.01–3.90, p < 0.001]. In the CKD group, the risk of SNHL (adjusted HR, 5.92) was higher among patients undergoing hemodialysis than among those not undergoing hemodialysis (adjusted HR, 1.40). Furthermore, subgroup analysis revealed an increased risk of SNHL in patients with CKD and comorbidities, including heart failure (adjusted HR, 7.48), liver cirrhosis (adjusted HR, 4.12), type 2 diabetes mellitus (adjusted HR, 3.98), hypertension (adjusted HR, 3.67), and chronic obstructive pulmonary disease (adjusted HR, 3.45). CKD is an independent risk of developing SNHL. Additionally, hemodialysis for uremia can increase the risk of SNHL. Cardiovascular, lung, liver, and metabolic comorbidities in CKD patients may further aggravate the risk of SNHL by inter-organ crosstalk. We should pay attention to SNHL in this high-risk population.
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Yoon JH, Lee JM, Lee DH, Joo I, Jeon JH, Ahn SJ, Kim ST, Cho EJ, Lee JH, Yu SJ, Kim YJ, Yoon JH. A Comparison of Biannual Two-Phase Low-Dose Liver CT and US for HCC Surveillance in a Group at High Risk of HCC Development. Liver Cancer 2020; 9:503-517. [PMID: 33083277 PMCID: PMC7548851 DOI: 10.1159/000506834] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Accepted: 02/26/2020] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND AND AIMS Biannual ultrasonography (US) is a current recommendation for hepatocellular carcinoma (HCC) surveillance in a high-risk group. The sensitivity of US, however, has been low in patients with a high risk of developing HCC. We aimed to compare sensitivity for HCC of biannual US and two-phase low-dose computed tomography (LDCT) in patients with a high risk of HCC. METHODS In this prospective single-arm study, participants with an annual risk of HCC greater than 5% (based on a risk index of ≥2.33) and who did not have a history of HCC were enrolled from November 2014 to July 2016. Participants underwent paired biannual US and two-phase LDCT 1-3 times. Two-phase LDCT included arterial and 3-min delayed phases. The sensitivity, specificity, and positive predictive value of HCC detection using US and two-phase LDCT were compared using a composite algorithm as a standard of reference. RESULTS Of the 139 enrolled participants, 137 underwent both the biannual US and two-phase LDCT at least once and had follow-up images. Among them, 27 cases of HCC (mean size: 14 ± 4 mm) developed in 24 participants over 1.5 years. Two-phase LDCT showed a significantly higher sensitivity (83.3% [20/24] vs. 29.2% [7/24], p < 0.001) and specificity (95.6% [108/113] vs. 87.7% [99/113], p =0.03) than US. A false-positive result was reported in 14 participants at US and 5 participants at two-phase LDCT, resulting in a significantly higher positive predictive value of two-phase LDCT (33.3% [7/21] vs. 80% [20/25], p < 0.001). CONCLUSIONS Patients with a risk index ≥2.33 showed a high annual incidence of HCC development in our study, and two-phase LDCT showed significantly higher sensitivity and specificity for HCC detection than US.
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Affiliation(s)
- Jeong Hee Yoon
- Radiology, Seoul National University Hospital, Seoul, Republic of Korea,College of Medicine, Seoul, Republic of Korea
| | - Jeong Min Lee
- Radiology, Seoul National University Hospital, Seoul, Republic of Korea,College of Medicine, Seoul, Republic of Korea,Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea,*Jeong Min Lee, Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080 (Republic of Korea),
| | - Dong Ho Lee
- Radiology, Seoul National University Hospital, Seoul, Republic of Korea,College of Medicine, Seoul, Republic of Korea
| | - Ijin Joo
- Radiology, Seoul National University Hospital, Seoul, Republic of Korea,College of Medicine, Seoul, Republic of Korea
| | - Ju Hyun Jeon
- Radiology, Seoul National University Hospital, Seoul, Republic of Korea,College of Medicine, Seoul, Republic of Korea
| | - Su Joa Ahn
- Radiology, Seoul National University Hospital, Seoul, Republic of Korea,College of Medicine, Seoul, Republic of Korea
| | - Seung-taek Kim
- Radiology, Seoul National University Hospital, Seoul, Republic of Korea,College of Medicine, Seoul, Republic of Korea
| | - Eun Ju Cho
- Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jeong-Hoon Lee
- Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Su Jong Yu
- Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Yoon Jun Kim
- Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jung-Hwan Yoon
- Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
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Inoue T, Tanaka Y. Novel biomarkers for the management of chronic hepatitis B. Clin Mol Hepatol 2020; 26:261-279. [PMID: 32536045 PMCID: PMC7364351 DOI: 10.3350/cmh.2020.0032] [Citation(s) in RCA: 89] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Revised: 04/11/2020] [Accepted: 04/13/2020] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) cannot be eliminated completely from infected hepatocytes because of the presence of intrahepatic covalently closed circular DNA (cccDNA). As chronic hepatitis B (CHB) can progress to cirrhosis and hepatocellular carcinoma (HCC), it is important to manage CHB to prevent HCC development in high-risk patients with high viral replicative activity or advanced fibrosis. Serum biomarkers are noninvasive and valuable for the management of CHB. Hepatitis B core-related antigen (HBcrAg) correlates with serum HBV DNA and intrahepatic cccDNA. In CHB patients with undetectable serum HBV DNA or loss of HBsAg, HBcrAg still can be detected and the decrease in HBcrAg levels is significantly associated with hopeful outcomes. Therefore, HBcrAg can predict HCC occurrence or recurrence. Measurement of the Mac-2 binding protein glycosylation isomer (M2BPGi) has been introduced for the evaluation of liver fibrosis. Because elevated M2BPGi in CHB is related to liver fibrosis and the prediction of HCC development, monitoring its progression is essential. Because alpha fetoprotein (AFP) has insufficient sensitivity and specificity for early-stage HCC, a combination of AFP plus protein induced by vitamin K absence factor II, or AFP plus Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein might improve the diagnosis of HCC development. Additionally, Dickkopf-1 and circulating immunoglobulin G antibodies are the novel markers to diagnose HCC or assess HCC prognosis. This review provides an overview of novel HBV biomarkers used for the management of intrahepatic viral replicative activity, liver fibrosis, and HCC development.
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Affiliation(s)
- Takako Inoue
- Department of Clinical Laboratory Medicine, Nagoya City University Hospital, Nagoya, Japan
| | - Yasuhito Tanaka
- Department of Clinical Laboratory Medicine, Nagoya City University Hospital, Nagoya, Japan
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
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Park HJ, Jang HY, Kim SY, Lee SJ, Won HJ, Byun JH, Choi SH, Lee SS, An J, Lim YS. Non-enhanced magnetic resonance imaging as a surveillance tool for hepatocellular carcinoma: Comparison with ultrasound. J Hepatol 2020; 72:718-724. [PMID: 31836549 DOI: 10.1016/j.jhep.2019.12.001] [Citation(s) in RCA: 96] [Impact Index Per Article: 19.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Revised: 11/27/2019] [Accepted: 12/01/2019] [Indexed: 12/25/2022]
Abstract
BACKGROUND & AIMS Recently revised international guidelines for hepatocellular carcinoma (HCC) suggest that patients with inadequate ultrasonography be assessed by alternative imaging modalities. Non-enhanced MRI has potential as a surveillance tool based on the short scan times required and the absence of contrast agent-associated risks. This study compared the performance of non-enhanced MRI and ultrasonography for HCC surveillance in high-risk patients. METHODS We included 382 high-risk patients in a prospective cohort who underwent 1 to 3 rounds of paired gadoxetic acid-enhanced MRI and ultrasonography. Non-enhanced MRI, consisting of diffusion-weighted imaging (DWI) and T2-weighted imaging, was simulated and retrospectively analyzed, with results considered positive when lesion(s) ≥1 cm showed diffusion restriction or mild-moderate T2 hyperintensity. Ultrasonography results were retrieved from patient records. HCC was diagnosed histologically and/or radiologically. Sensitivity, positive predictive value (PPV), specificity, and negative predictive value (NPV) were evaluated using generalized estimating equations. RESULTS Forty-eight HCCs were diagnosed in 43 patients. Per-lesion and per-exam sensitivities of non-enhanced MRI were 77.1% and 79.1%, respectively, which were higher than those achieved with ultrasonography (25.0% and 27.9%, respectively, p <0.001). Specificities of non-enhanced MRI (97.9%) and ultrasonography (94.5%) differed significantly (p <0.001). NPV was higher for non-enhanced MRI (99.1%) than ultrasonography (96.9%). Per-lesion and per-exam PPVs were higher for non-enhanced MRI (56.9% and 61.8%, respectively) than for ultrasonography (16.7% and 17.7%, respectively). The estimated scan time of non-enhanced MRI was <6 min. CONCLUSION Based on its good performance, short scan times, and the lack of contrast agent-associated risks, non-enhanced MRI is a promising option for HCC surveillance in high-risk patients. LAY SUMMARY Recently revised international guidelines for hepatocellular carcinoma (HCC) suggest that selected patients with inadequate surveillance on ultrasonography be assessed by alternative imaging modalities such as computed tomography or magnetic resonance imaging (MRI). Herein, we show that MRI without contrast agents performed significantly better than ultrasonography for HCC surveillance in high-risk patients. Given this good performance, as well as short scan times and the lack of contrast agent-associated risks, non-enhanced MRI is a promising option for HCC surveillance in high-risk patients.
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Affiliation(s)
- Hyo Jung Park
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Hye Young Jang
- Department of Radiology, National Cancer Center, Gyeonggi-do, Republic of Korea
| | - So Yeon Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
| | - So Jung Lee
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Hyung Jin Won
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jae Ho Byun
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sang Hyun Choi
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Seung Soo Lee
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jihyun An
- Department of Gastroenterology and Hepatology, Hanyang University of Medicine, Guri, Republic of Korea
| | - Young-Suk Lim
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Jo H, Lee J, Jeon J, Kim SY, Chung JI, Ko HY, Lee M, Yun M. The critical role of glucose deprivation in epithelial-mesenchymal transition in hepatocellular carcinoma under hypoxia. Sci Rep 2020; 10:1538. [PMID: 32001727 PMCID: PMC6992695 DOI: 10.1038/s41598-020-58124-1] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Accepted: 01/06/2020] [Indexed: 12/30/2022] Open
Abstract
Imaging with 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is used to determine sites of abnormal glucose metabolism to predict high tumor grade, metastasis, and poor patient survival. However, not all tumors with increased 18F-FDG uptake show aggressive tumor biology, as evident from the moderate correlation between metastasis and high FDG uptake. We hypothesized that metastasis is likely attributable to the complexity and heterogeneity of the cancer microenvironment. To identify the cancer microenvironment that induces the epithelial-mesenchymal transition (EMT) process, tumor areas of patients with HCC were analyzed by immunostaining. Our data demonstrated the induction of EMT process in HCC cells with low proliferation under hypoxic conditions. To validate our finding, among HCC cell lines, HepG2 cells with highly increased expression of HIF1α under hypoxia were employed in vitro and in vivo. Major changes in EMT-associated protein expression, such as the up-regulation of N-cadherin and snail/slug are associated with decreased proliferation-related protein (PCNA) caused by glucose deprivation under hypoxia. Indeed, PCNA knockdown-HepG2 cells under hypoxia showed the induction of more EMT process compare to the control. Thus, HCC cells with low proliferative potential under glucose-deprived and hypoxic conditions show high probability for induced EMT process and promote cell invasion. This study investigates reasons as to why an EMT process cannot fully be predicted. Our observations indicate that rather than analyzing a single factor, an integrated analysis of hypoxia with low glucose metabolism and low cell proliferation might be helpful to predict the potential impact on induction of EMT process and promotion of cell invasion.
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Affiliation(s)
- Hanhee Jo
- Division of Life Sciences, College of Life Science and Bioengineering, Incheon National University, Incheon, South Korea
| | - Jongsook Lee
- Division of Life Sciences, College of Life Science and Bioengineering, Incheon National University, Incheon, South Korea
| | - Jeongyong Jeon
- Department of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Seon Yoo Kim
- Department of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Jee-In Chung
- Department of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Hae Yong Ko
- Department of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Misu Lee
- Division of Life Sciences, College of Life Science and Bioengineering, Incheon National University, Incheon, South Korea.
| | - Mijin Yun
- Department of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
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Shao LN, Zhang ST, Wang N, Yu WJ, Chen M, Xiao N, Duan Y, Pan LZ, Song WQ, Xia YX, Zhang L, Qi N, Liu M, Zhou SH. Platelet indices significantly correlate with liver fibrosis in HCV-infected patients. PLoS One 2020; 15:e0227544. [PMID: 31917827 PMCID: PMC6952095 DOI: 10.1371/journal.pone.0227544] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Accepted: 11/22/2019] [Indexed: 12/14/2022] Open
Abstract
AIM A total of 241 patients with chronic HCV infection were recruited to investigate the association between liver fibrosis and PLT counts, as well as with MPV, PDW and P-LCR indices. METHODS The determination of PLT indices was carried out using a Sysmex XT-1800i automated hematology analyzer. Serological tests for HA, LN, C-IV and PIIINP were performed in 210 patients. The liver stiffness was measured in 69 patients by transient elastography (FibroScan). RESULTS The analysis showed that the four serum fibrosis markers were negatively correlated with PLT counts, but positively correlated with the MPV, PDW and P-LCR values. Moreover, a similar pattern was found after analyzing the FibroScan measurements, which were negatively correlated with PLT counts, but positively correlated with MPV, PDW and P-LCR values. We subdivided the HCV-infected patients into mild and advanced fibrosis groups. The PLT counts were significantly decreased and the MPV, PDW and P-LCR values were significantly increased in the advanced fibrosis group when compared with the mild fibrosis group. CONCLUSIONS Our results demonstrate that not only the PLT counts but also the MPV, PDW and P-LCR indices significantly correlate with liver fibrosis in HCV-infected patients. Therefore, these indices may be useful laboratory measures for evaluating liver fibrosis progression.
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Affiliation(s)
- Lin-Nan Shao
- Dalian Blood Center, Zhongshan District, Dalian, Liaoning, China
| | - Shu-Ting Zhang
- Dalian Blood Center, Zhongshan District, Dalian, Liaoning, China
| | - Ni Wang
- Dalian Blood Center, Zhongshan District, Dalian, Liaoning, China
| | - Wei-Jian Yu
- Dalian Blood Center, Zhongshan District, Dalian, Liaoning, China
| | - Mei Chen
- Dalian Blood Center, Zhongshan District, Dalian, Liaoning, China
| | - Nan Xiao
- Dalian Blood Center, Zhongshan District, Dalian, Liaoning, China
| | - Ying Duan
- Dalian Blood Center, Zhongshan District, Dalian, Liaoning, China
| | - Ling-Zi Pan
- Dalian Blood Center, Zhongshan District, Dalian, Liaoning, China
| | - Wen-Qian Song
- Dalian Blood Center, Zhongshan District, Dalian, Liaoning, China
| | - Yue-Xin Xia
- Dalian Blood Center, Zhongshan District, Dalian, Liaoning, China
| | - Li Zhang
- Dalian Blood Center, Zhongshan District, Dalian, Liaoning, China
| | - Ning Qi
- Dalian Blood Center, Zhongshan District, Dalian, Liaoning, China
| | - Ming Liu
- Department of Cell Biology, Dalian Medical University, Dalian, Liaoning, China
| | - Shi-Hang Zhou
- Dalian Blood Center, Zhongshan District, Dalian, Liaoning, China
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Son JH, Choi SH, Kim SY, Jang HY, Byun JH, Won HJ, Lee SJ, Lim YS. Validation of US Liver Imaging Reporting and Data System Version 2017 in Patients at High Risk for Hepatocellular Carcinoma. Radiology 2019; 292:390-397. [PMID: 31210614 DOI: 10.1148/radiol.2019190035] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Background The 2017 version of the Liver Imaging Reporting and Data System (LI-RADS) recently included standardized interpretation, reporting, and management guidelines for US (US LI-RADS); however, this system has not yet been validated. Purpose To evaluate the diagnostic performance of US LI-RADS version 2017 for detecting hepatocellular carcinoma (HCC) in participants at high risk and to determine the clinical factors associated with a poor visualization score. Materials and Methods This study included 407 prospectively recruited participants (mean age, 56 years; age range, 28-76 years) with cirrhosis at high risk for HCC who underwent US surveillance from November 2011 to August 2012. Two radiologists retrospectively analyzed US images, assigning a LI-RADS category (US-1 = negative, US-2 = subthreshold, US-3 = positive) and a visualization score (A = no or minimal limitations, B = moderate limitations, C = severe limitations). The sensitivity and specificity for diagnosing HCC were calculated on a per-patient and per-lesion basis, using pathologic results and typical CT or MRI as reference standards. The risk factors for a poor visualization score were determined by using univariable and multivariable analyses. Results Of 429 lesions in 407 participants, there were 32 HCCs in 28 participants. In the per-lesion analysis, the specificity for US-3 was 366 of 397 (92%; 95% confidence interval [CI]: 89%, 95%) and the sensitivity was 11 of 32 (34%; 95% CI: 20%, 52%). In the per-patient analysis, the specificity for US-3 was 352 of 379 (93%; 95% CI: 90%, 95%) and the sensitivity was 11 of 28 (39%; 95% CI: 24%, 58%). Visualization score C (114 of 407 [28%] participants) had the highest false-negative rate (six of seven [86%] participants). High body weight (adjusted odds ratio [OR], 2.1 [95% CI: 1.2, 3.6]; P = .01), Child-Pugh class B disease (OR, 2.9 [95% CI: 1.7, 4.9]; P < .001), and moderate to severe fatty liver (OR, 1.7 [95% CI: 1.0, 2.8]; P = .047) were associated with a poor visualization score of C. Conclusion The US-3 category demonstrated high specificity but low sensitivity for diagnosing hepatocellular carcinoma. The visualization score C had a higher false-negative rate than scores A or B, and patients with high body weight, Child-Pugh class B disease, and moderate to severe fatty liver may present limitations for US surveillance. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Milot in this issue.
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Affiliation(s)
- Jung Hee Son
- From the Department of Radiology and Research Institute of Radiology (J.H.S., S.H.C., S.Y.K., J.H.B., H.J.W., S.J.L.), and Department of Gastroenterology (Y.S.L.), University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, South Korea; Department of Radiology, National Cancer Center, Goyang, South Korea (H.Y.J.)
| | - Sang Hyun Choi
- From the Department of Radiology and Research Institute of Radiology (J.H.S., S.H.C., S.Y.K., J.H.B., H.J.W., S.J.L.), and Department of Gastroenterology (Y.S.L.), University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, South Korea; Department of Radiology, National Cancer Center, Goyang, South Korea (H.Y.J.)
| | - So Yeon Kim
- From the Department of Radiology and Research Institute of Radiology (J.H.S., S.H.C., S.Y.K., J.H.B., H.J.W., S.J.L.), and Department of Gastroenterology (Y.S.L.), University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, South Korea; Department of Radiology, National Cancer Center, Goyang, South Korea (H.Y.J.)
| | - Hye Young Jang
- From the Department of Radiology and Research Institute of Radiology (J.H.S., S.H.C., S.Y.K., J.H.B., H.J.W., S.J.L.), and Department of Gastroenterology (Y.S.L.), University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, South Korea; Department of Radiology, National Cancer Center, Goyang, South Korea (H.Y.J.)
| | - Jae Ho Byun
- From the Department of Radiology and Research Institute of Radiology (J.H.S., S.H.C., S.Y.K., J.H.B., H.J.W., S.J.L.), and Department of Gastroenterology (Y.S.L.), University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, South Korea; Department of Radiology, National Cancer Center, Goyang, South Korea (H.Y.J.)
| | - Hyung Jin Won
- From the Department of Radiology and Research Institute of Radiology (J.H.S., S.H.C., S.Y.K., J.H.B., H.J.W., S.J.L.), and Department of Gastroenterology (Y.S.L.), University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, South Korea; Department of Radiology, National Cancer Center, Goyang, South Korea (H.Y.J.)
| | - So Jung Lee
- From the Department of Radiology and Research Institute of Radiology (J.H.S., S.H.C., S.Y.K., J.H.B., H.J.W., S.J.L.), and Department of Gastroenterology (Y.S.L.), University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, South Korea; Department of Radiology, National Cancer Center, Goyang, South Korea (H.Y.J.)
| | - Young Suk Lim
- From the Department of Radiology and Research Institute of Radiology (J.H.S., S.H.C., S.Y.K., J.H.B., H.J.W., S.J.L.), and Department of Gastroenterology (Y.S.L.), University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, South Korea; Department of Radiology, National Cancer Center, Goyang, South Korea (H.Y.J.)
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Yamada R, Hiramatsu N, Oze T, Urabe A, Tahata Y, Morishita N, Kodama T, Hikita H, Sakamori R, Yakushijin T, Yamada A, Hagiwara H, Mita E, Oshita M, Itoh T, Fukui H, Inui Y, Hijioka T, Inada M, Katayama K, Tamura S, Inoue A, Imai Y, Tatsumi T, Hamasaki T, Hayashi N, Takehara T. Incidence and risk factors of hepatocellular carcinoma change over time in patients with hepatitis C virus infection who achieved sustained virologic response. Hepatol Res 2019; 49:570-578. [PMID: 30623521 DOI: 10.1111/hepr.13310] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2018] [Revised: 11/09/2018] [Accepted: 12/26/2018] [Indexed: 01/08/2023]
Abstract
AIM In patients with chronic hepatitis C, hepatocellular carcinoma (HCC) occurs at a certain frequency, even if a sustained virologic response (SVR) is achieved by antiviral treatment. Old age, liver fibrosis, and high post-treatment α-fetoprotein (AFP) level are typical risk factors of post-SVR HCC. We examined whether the frequencies and factors of HCC in patients with an SVR achieved from interferon treatment changed. Methods Among patients prospectively registered for pegylated interferon and ribavirin treatment, 2021 with an SVR without HCC development during the treatment period were followed up. The mean observation period was 49.5 ± 26.2 months. RESULTS The multivariable Cox regression analysis showed that older age, diabetes mellitus, advanced liver disease, and higher post-treatment AFP level were the independent risk factors throughout the observation period. The annual occurrence rate of HCC was 0.74% in the third year, 0.54% in the fourth year, and 0.40% in the fifth year; it gradually decreased from the third year. Because the time course hazards for HCC changed at 48 months, we separately analyzed its risk factors before and after this change point. The multivariable Cox regression analysis showed that the four above-mentioned factors were significantly related to HCC development within 4 years. Conversely, the univariable Cox regression analysis only identified diabetes mellitus as a significant factor for HCC development after 4 years. CONCLUSION The frequency of HCC in hepatitis C patients who achieved an SVR from interferon treatment decreased during the observation period, and its risk factors changed between the early and late periods.
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Affiliation(s)
- Ryoko Yamada
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita
| | - Naoki Hiramatsu
- Department of Gastroenterology and Hepatology, Osaka Rosai Hospital, Sakai
| | - Tsugiko Oze
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita
| | - Ayako Urabe
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita
| | - Yuki Tahata
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita
| | - Naoki Morishita
- Department of Gastroenterology and Hepatology, Minoh City Hospital, Minoh
| | - Takahiro Kodama
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita
| | - Hayato Hikita
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita
| | - Ryotaro Sakamori
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita
| | - Takayuki Yakushijin
- Department of Gastroenterology and Hepatology, Osaka General Medical Center, Osaka
| | - Akira Yamada
- Department of Gastroenterology and Hepatology, Sumitomo Hospital, Osaka
| | - Hideki Hagiwara
- Department of Gastroenterology and Hepatology, Kansai Rosai Hospital, Amagasaki
| | - Eiji Mita
- Department of Gastroenterology and Hepatology, National Hospital Organization Osaka National Hospital, Osaka
| | - Masahide Oshita
- Department of Gastroenterology and Hepatology, Osaka Police Hospital, Osaka
| | - Toshifumi Itoh
- Department of Gastroenterology and Hepatology, Japan Community Health care Organization Osaka Hospital, Osaka
| | - Hiroyuki Fukui
- Department of Gastroenterology and Hepatology, Yao Municipal Hospital, Yao
| | - Yoshiaki Inui
- Department of Gastroenterology and Hepatology, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya
| | - Taizo Hijioka
- Department of Gastroenterology and Hepatology, National Hospital Organization Osaka Minami Medical Center, Kawachinagano
| | - Masami Inada
- Department of Gastroenterology and Hepatology, Toyonaka Municipal Hospital, Toyonaka
| | - Kazuhiro Katayama
- Department of Gastroenterology and Hepatology, Osaka International Cancer Institute, Osaka
| | - Shinji Tamura
- Department of Gastroenterology and Hepatology, Minoh City Hospital, Minoh
| | - Atsuo Inoue
- Department of Gastroenterology and Hepatology, Osaka General Medical Center, Osaka
| | - Yasuharu Imai
- Department of Gastroenterology and Hepatology, Ikeda Municipal Hospital, Ikeda
| | - Tomohide Tatsumi
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita
| | - Toshimitsu Hamasaki
- Department of Gastroenterology and Hepatology, Department of Data Science, National Cerebral and Cardiovascular Center, Suita, Japan
| | - Norio Hayashi
- Department of Gastroenterology and Hepatology, Kansai Rosai Hospital, Amagasaki
| | - Tetsuo Takehara
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita
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Kim W, Jeong D, Chung J, Lee D, Joo S, Jang ES, Choi YJ, Yoon H, Shin CM, Park YS, Jeong SH, Kim N, Lee DH, Kim JW. Development of colorectal cancer predicts increased risk of subsequent hepatocellular carcinoma in patients with alcoholic liver disease: case-control and cohort study. Sci Rep 2019; 9:3236. [PMID: 30824851 PMCID: PMC6397178 DOI: 10.1038/s41598-019-39573-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Accepted: 01/24/2019] [Indexed: 11/09/2022] Open
Abstract
Alcohol increases the risk of both hepatocellular carcinoma (HCC) and colorectal neoplasia. In this hospital-based case-control and retrospective cohort study, we sought to determine whether development of colorectal neoplasia increases the risk of HCC in patients with alcoholic liver disease (ALD). In the phase I case-control analysis, the association between history of colorectal cancer (CRC) and HCC development was assessed in patients with ALD by logistic regression modeling (n = 1,659). In the phase II retrospective cohort analysis, the relative risk of HCC development was compared in ALD patients with respect to the history of CRC by a Cox model (n = 1,184). The history of CRC was significantly associated with HCC in the case-control analysis (adjusted odds ratio, 1.82; 95% CI, 1.06-3.15; P < 0.05). ALD patients with CRC had higher risk of developing HCC compared to those without CRC (adjusted hazards ratio [HR], 5.48; 95% CI, 1.63-18.36; P = 0.006) in the cohort analysis. Presence of CRC, liver cirrhosis, elevated baseline alpha-fetoprotein level, and low platelet counts were independent predictors of HCC development in ALD patients. Patients with history of CRC had an increased risk of HCC in both cirrhotic (HR, 3.76; 95% CI, 1.05-13.34, P = 0.041) and non-cirrhotic (HR, 23.46; 95% CI, 2.81-195.83, P = 0.004) ALD patients. In conclusion, ALD patients with CRC are at increased risk of developing HCC.
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Affiliation(s)
- Won Kim
- Department of Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.,Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Republic of Korea
| | - Dongjae Jeong
- Department of Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jungwha Chung
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Donghyeon Lee
- Department of Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.,Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Republic of Korea
| | - Saekyoung Joo
- Department of Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.,Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Republic of Korea
| | - Eun Sun Jang
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Yoon Jin Choi
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Hyuk Yoon
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Cheol Min Shin
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Young Soo Park
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Sook-Hyang Jeong
- Department of Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.,Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Nayoung Kim
- Department of Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Dong Ho Lee
- Department of Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.,Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Jin-Wook Kim
- Department of Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. .,Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
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41
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Tarao K, Nozaki A, Ikeda T, Sato A, Komatsu H, Komatsu T, Taguri M, Tanaka K. Real impact of liver cirrhosis on the development of hepatocellular carcinoma in various liver diseases-meta-analytic assessment. Cancer Med 2019; 8:1054-1065. [PMID: 30791221 PMCID: PMC6434205 DOI: 10.1002/cam4.1998] [Citation(s) in RCA: 106] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2018] [Revised: 12/27/2018] [Accepted: 01/06/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND It is well known that the incidence of developing hepatocelluler carcinoma (HCC) is increased in liver cirrhosis of different etiologies. However, comparison of HCC incidence in various liver diseases has not yet been estimated. We surveyed this comparison. METHODS The PubMed database was examined (1989-2017) for studies published in English language regarding the prospective follow-up results for the development of HCC in various liver diseases. A meta-analysis was performed for each liver disease. RESULTS The annual incidence (%) of HCC in the non-cirrhotic stage and cirrhotic stage, and the ratio of HCC incidence in the cirrhotic stage/non-cirrhotic stage were as follows. (a) hepatitis B virus liver disease: 0.37%→3.23% (8.73-fold), (b) hepatitis C virus liver diseases: 0.68%→4.81% (7.07-fold), (c) primary biliary cholangitis (0.26%→1.79%, 6.88-fold), (d) autoimmune hepatitis (0.19%→0.53%, 2.79-fold), and (e) NASH (0.03%→1.35%, 45.00-fold). Regarding primary hemochromatosis and alcoholic liver diseases, only follow-up studies in the cirrhotic stage were presented, 1.20% and 2.06%, respectively. CONCLUSIONS When the liver diseases advance to cirrhosis, the incidence of HCC is markedly increased. The development of HCC must be closely monitored by ultrasonography, magnetic resonance imaging, and computed tomography, irrespective of the different kinds of liver diseases.
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Affiliation(s)
- Kazuo Tarao
- Tarao’s Gastroenterological ClinicYokohamaJapan
| | - Akito Nozaki
- Gastroenterological Center, Medical CenterYokohama City UniversityYokohamaJapan
| | - Takaaki Ikeda
- Gastroenterology DepartmentYokosuka General Hospital UwamachiYokosukaJapan
| | - Akira Sato
- Division of Gastroenterology, Department of Internal MedicineSt. Marianna University, Yokohama City Seibu HospitalYokohamaJapan
| | - Hirokazu Komatsu
- Department of GastroenterologyYokohama Municipal Citizen’s HospitalYokohamaJapan
| | - Tatsuji Komatsu
- Department Clinical ResearchNational Hospital Organization, Yokohama Medical CenterYokohamaJapan
| | - Masataka Taguri
- Department of Data ScienceYokohama City UniversityYokohamaJapan
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42
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Liu L, Fu L, Zhang JW, Wei H, Ye WL, Deng ZK, Zhang L, Cheng Y, Ouyang D, Cao Q, Cao DS. Three-Level Hepatotoxicity Prediction System Based on Adverse Hepatic Effects. Mol Pharm 2018; 16:393-408. [PMID: 30475633 DOI: 10.1021/acs.molpharmaceut.8b01048] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
Hepatotoxicity is a major cause of drug withdrawal from the market. To reduce the drug attrition induced by hepatotoxicity, an accurate and efficient hepatotoxicity prediction system must be constructed. In the present study, we constructed a three-level hepatotoxicity prediction system based on different levels of adverse hepatic effects (AHEs) combined with machine learning, using (1) an end point, hepatotoxicity; (2) four hepatotoxicity severity degrees; and (3) specific AHEs. After collecting and curing 15 873 compound-AHE pairs associated with 2017 compounds and 403 AHEs, we constructed 27 models with three end point levels with the random forest algorithm, and obtained accuracies ranging from 67.0 to 78.2% and the area under receiver operating characteristic curves (AUCs) of 0.715-0.875. The 27 models were fully integrated into a tiered hepatotoxicity prediction system. The existence of hepatotoxicity existence, severity degree, and potential AHEs for a given compound could be inferred simultaneously and systematically. Thus, the tiered hepatotoxicity prediction system allows researchers to have significant confidence in confirming compound hepatotoxicity, analyzing hepatotoxicity from multiple perspectives, obtaining warnings for the potential hepatotoxicity severity, and even rapidly selecting the proper in vitro experiments for hepatotoxicity verification. We also applied three external sets (11 drugs or candidates that failed in clinical trials or were withdrawn from the market, the PharmGKB (offsides) database, and an herbal hepatotoxicity data set) to test and validate the prediction ability of our system. Furthermore, the hepatotoxicity prediction system was adapted into a flow framework based on the Konstanz Information Miner, which was made available for researchers.
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Affiliation(s)
- Lu Liu
- Xiangya School of Pharmaceutical Sciences , Central South University , Changsha , People's Republic of China
| | - Li Fu
- Xiangya School of Pharmaceutical Sciences , Central South University , Changsha , People's Republic of China
| | - Jin-Wei Zhang
- Xiangya School of Pharmaceutical Sciences , Central South University , Changsha , People's Republic of China
| | - Hui Wei
- Xiangya School of Pharmaceutical Sciences , Central South University , Changsha , People's Republic of China
| | - Wen-Ling Ye
- Xiangya School of Pharmaceutical Sciences , Central South University , Changsha , People's Republic of China
| | - Zhen-Ke Deng
- Xiangya School of Pharmaceutical Sciences , Central South University , Changsha , People's Republic of China
| | - Lin Zhang
- Hunan Key Laboratory of Processed Food for Special Medical Purpose Central South University of Forestry and Technology , Changsha 410004 , People's Republic of China
| | - Yan Cheng
- Xiangya School of Pharmaceutical Sciences , Central South University , Changsha , People's Republic of China
| | - Defang Ouyang
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences (ICMS) , University of Macau , Macau , China
| | - Qian Cao
- Beijing Rehabilitation Hospital Affiliated to Capital Medical University , Beijing 100001 , People's Republic of China
| | - Dong-Sheng Cao
- Xiangya School of Pharmaceutical Sciences , Central South University , Changsha , People's Republic of China
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Lee M, Ko H, Yun M. Cancer Metabolism as a Mechanism of Treatment Resistance and Potential Therapeutic Target in Hepatocellular Carcinoma. Yonsei Med J 2018; 59:1143-1149. [PMID: 30450847 PMCID: PMC6240564 DOI: 10.3349/ymj.2018.59.10.1143] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2018] [Indexed: 12/14/2022] Open
Abstract
Various molecular targeted therapies and diagnostic modalities have been developed for the treatment of hepatocellular carcinoma (HCC); however, HCC still remains a difficult malignancy to cure. Recently, the focus has shifted to cancer metabolism for the diagnosis and treatment of various cancers, including HCC. In addition to conventional diagnostics, the measurement of enhanced tumor cell metabolism using F-18 fluorodeoxyglucose (18F-FDG) for increased glycolysis or C-11 acetate for fatty acid synthesis by positron emission tomography/computed tomography (PET/CT) is well established for clinical management of HCC. Unlike tumors displaying the Warburg effect, HCCs vary substantially in terms of 18F-FDG uptake, which considerably reduces the sensitivity for tumor detection. Accordingly, C-11 acetate has been proposed as a complementary radiotracer for detecting tumors that are not identified by 18F-FDG. In addition to HCC diagnosis, since the degree of 18F-FDG uptake converted to standardized uptake value (SUV) correlates well with tumor aggressiveness, 18F-FDG PET/CT scans can predict patient outcomes such as treatment response and survival with an inverse relationship between SUV and survival. The loss of tumor suppressor genes or activation of oncogenes plays an important role in promoting HCC development, and might be involved in the "metabolic reprogramming" of cancer cells. Mutations in various genes such as TERT, CTNNB1, TP53, and Axin1 are responsible for the development of HCC. Some microRNAs (miRNAs) involved in cancer metabolism are deregulated in HCC, indicating that the modulation of genes/miRNAs might affect HCC growth or metastasis. In this review, we will discuss cancer metabolism as a mechanism for treatment resistance, as well as an attractive potential therapeutic target in HCC.
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Affiliation(s)
- Misu Lee
- Department of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
- Division of Life Science, College of Life Science and Bioengineering, Incheon National University, Incheon, Korea
| | - Haeyong Ko
- Department of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Mijin Yun
- Department of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
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Wang Y, Attar BM, Hinami K, Fuentes HE, Jaiswal P, Zhang H, Simons-Linares CS, Tafur AJ. Characteristics and Impacts of Venous Thromboembolism in Patients with Hepatocellular Carcinoma. J Gastrointest Cancer 2018; 49:275-282. [PMID: 28374272 DOI: 10.1007/s12029-017-9945-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
INTRODUCTION Venous thromboembolism (VTE) is a common complication in cancer patients, and is associated with worse prognosis in such population. Hepatocellular carcinoma (HCC) poses high risk for VTE; however, data is scarce regarding the characteristics and consequences of VTE in HCC patients. METHOD We retrospectively reviewed the electronic medical records (EMR) of 270 patients diagnosed with HCC from 2000 to 2015 in Cook County Health and Hospitals System. We report the cumulative incidence of VTE in the present cohort, and identified through multivariate logistic regression the independent risk factors of the development of VTE. Overall prognosis of patients with and without VTE were presented and compared. RESULTS Sixteen cases (5.93%) of VTE were documented in the present study. In multivariate analysis, obesity, Child B cirrhosis, intra-hepatic lesions more than 3, and multi-organ extrahepatic metastasis were significantly associated with VTE development (p < 0.05). The presence of VTE was an independent risk factor for mortality in multivariate analysis (HR = 3.62, p = 0.021), together with male gender, Child C cirrhosis, and extrahepatic metastasis. CONCLUSIONS Obesity, Child B cirrhosis, more intra-hepatic lesions, and multi-organ extrahepatic metastasis are associated with cancer-associated VTE. VTE will adversely affect the prognosis of patients with HCC; therefore, primary thromboprophylaxis may be warranted in such population.
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Affiliation(s)
- Yuchen Wang
- Department of Internal Medicine, John H. Stroger, Jr. Hospital of Cook County, 1900 West Polk Street, Chicago, IL, 60612, USA.
| | - B M Attar
- Division of Gastroenterology and Hepatology, John H. Stroger, Jr. Hospital of Cook County, Chicago, IL, USA.,Department of Gastroenterology, Rush University Medical Center, Chicago, IL, USA
| | - K Hinami
- Collaborative Research Unit, John H. Stroger, Jr. Hospital of Cook County, Chicago, IL, USA
| | - H E Fuentes
- Department of Internal Medicine, John H. Stroger, Jr. Hospital of Cook County, 1900 West Polk Street, Chicago, IL, 60612, USA
| | - P Jaiswal
- Department of Internal Medicine, John H. Stroger, Jr. Hospital of Cook County, 1900 West Polk Street, Chicago, IL, 60612, USA
| | - H Zhang
- Collaborative Research Unit, John H. Stroger, Jr. Hospital of Cook County, Chicago, IL, USA
| | - C S Simons-Linares
- Department of Internal Medicine, John H. Stroger, Jr. Hospital of Cook County, 1900 West Polk Street, Chicago, IL, 60612, USA
| | - A J Tafur
- Cardiology-Vascular Medicine, NorthShore University HealthSystem, Evanston, IL, USA
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45
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Indian Hedgehog links obesity to development of hepatocellular carcinoma. Oncogene 2018; 38:2206-2222. [PMID: 30470823 DOI: 10.1038/s41388-018-0585-5] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2018] [Revised: 10/10/2018] [Accepted: 10/12/2018] [Indexed: 02/07/2023]
Abstract
Obesity increases the risk of hepatocellular carcinoma (HCC), but precise identification and characterization of druggable oncogenic pathways that contribute to the progression of NAFLD to HCC, and hence to the increased incidence and aggressiveness of HCC in obese individuals is lacking. In this regard, we demonstrate that the Indian Hedgehog (Ihh) signaling pathway is upregulated in the fatty livers of mice consuming a high fat diet, and furthermore sustained in HCC tumors specifically within the context of a NAFLD microenvironment. Using a diet-induced mouse model of HCC wherein only obese mice develop HCC, targeted ablation of hepatocyte-secreted Ihh results in a decreased tumor burden and lower grade tumors. Ihh activation regulates the transdifferentiation of ciliated stellate cells and proliferation of Epcam+ ductal cells to promote fibrosis. Mechanistically, increased expression of hitherto uncharacterized effectors of Hh pathway, namely Myc and Tgf-β2 is critical to the observed physiology. This pro-tumorigenic response is driven by increased expression of Wnt5a to effect a poorly-differentiated and invasive tumor phenotype. Wnt5a secreted from activated stellate cells act on Ror2-expressing hepatocytes. We further demonstrate that Wnt5a expression is also elevated in poorly-differentiated HCC cells, suggesting that these ligands are also able to function in an autocrine positive feedback manner to sustain poorly-differentiated tumors. Taken together, our study provides a mechanistic understanding for how Ihh signaling promotes HCC tumorigenesis specifically in obese mice. We propose that therapeutic targeting of the Hh pathway offers benefit for patients with dietary / NAFLD-driven steatotic HCC.
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Zanetto A, Campello E, Spiezia L, Burra P, Simioni P, Russo FP. Cancer-Associated Thrombosis in Cirrhotic Patients with Hepatocellular Carcinoma. Cancers (Basel) 2018; 10:450. [PMID: 30453547 PMCID: PMC6266984 DOI: 10.3390/cancers10110450] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Revised: 11/02/2018] [Accepted: 11/13/2018] [Indexed: 12/24/2022] Open
Abstract
It is common knowledge that cancer patients are more prone to develop venous thromboembolic complications (VTE). It is therefore not surprising that patients with hepatocellular carcinoma (HCC) present with a significant risk of VTE, with the portal vein being the most frequent site (PVT). However, patients with HCC are peculiar as both cancer and liver cirrhosis are conditions that can perturb the hemostatic balance towards a prothrombotic state. Because HCC-related hypercoagulability is not clarified at all, the aim of the present review is to summarize the currently available knowledge on epidemiology and pathogenesis of non-malignant thrombotic complications in patients with liver cirrhosis and HCC. They are at increased risk to develop both PVT and non-splanchnic VTE, indicating that both local and systemic factors can foster the development of site-specific thrombosis. Recent studies have suggested multiple and often interrelated mechanisms through which HCC can tip the hemostatic balance of liver cirrhosis towards hypercoagulability. Described mechanisms include increased fibrinogen concentration/polymerization, thrombocytosis, and release of tissue factor-expressing extracellular vesicles. Currently, there are no specific guidelines on the use of thromboprophylaxis in this unique population. There is the urgent need of prospective studies assessing which patients have the highest prothrombotic profile and would therefore benefit from early thromboprophylaxis.
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Affiliation(s)
- Alberto Zanetto
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, 35128 Padua, Italy.
| | - Elena Campello
- Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, Padua University Hospital, 35128 Padua, Italy.
| | - Luca Spiezia
- Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, Padua University Hospital, 35128 Padua, Italy.
| | - Patrizia Burra
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, 35128 Padua, Italy.
| | - Paolo Simioni
- Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, Padua University Hospital, 35128 Padua, Italy.
| | - Francesco Paolo Russo
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, 35128 Padua, Italy.
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Kim KH, Lee SY, Hwang H, Lee JY, Ji ES, An HJ, Kim JY, Yoo JS. Direct Monitoring of Fucosylated Glycopeptides of Alpha-Fetoprotein in Human Serum for Early Hepatocellular Carcinoma by Liquid Chromatography-Tandem Mass Spectrometry with Immunoprecipitation. Proteomics Clin Appl 2018; 12:e1800062. [PMID: 29888876 DOI: 10.1002/prca.201800062] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2018] [Revised: 05/29/2018] [Indexed: 12/17/2022]
Abstract
PURPOSE Alpha-fetoprotein (AFP) is a widely used serological marker that is associated with hepatocellular carcinoma (HCC). Although the level of AFP is increased in HCC, its sensitivity for diagnosis is poor because AFP levels are also increased in liver diseases. Changes in glycoform, especially fucosylation, have been reported to be associated with the development of HCC. EXPERIMENTAL DESIGN The authors introduce the monitoring of fucosylated glycopeptides by liquid chromatography (LC)-mass spectrometry (MS) combined with immunoprecipitation, where glycan-cleaved fragments with an amino acid sequence are used as transitions. Furthermore, neuraminidase for desialylation is useful to improve the MS detection limit (limit of detection [LOD] <2 ng mL-1 ) in 0.1 μL of serum. RESULTS The performance of the relative percentage of fucosylated AFP (AFP-fuc%) for differentiating between early HCC and cirrhosis is better than that of serum AFP levels as indicated by a greater area under the receiver operator characteristic curve (area under the curve = 0.962 vs. 0.628) and sensitivity (92.3% vs. 53.9%), respectively. Furthermore, the inter- and intraday repeatability of AFP-fuc% in serum is less than 2.1%. CONCLUSIONS AND CLINICAL RELEVANCE These findings suggest that glycopeptide-based LC-MS/MS is a promising method and that AFP-fuc% is a clinically useful parameter for differentiating between early HCC and liver cirrhosis.
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Affiliation(s)
- Kwang Hoe Kim
- Biomedical Omics Research Group, Korea Basic Science Institute, Cheongju, Ochang-eup, 28119, Republic of Korea
- Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, 34134, Republic of Korea
| | - Soo-Youn Lee
- Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Republic of Korea
| | - Heeyoun Hwang
- Biomedical Omics Research Group, Korea Basic Science Institute, Cheongju, Ochang-eup, 28119, Republic of Korea
| | - Ju Yeon Lee
- Biomedical Omics Research Group, Korea Basic Science Institute, Cheongju, Ochang-eup, 28119, Republic of Korea
| | - Eun Sun Ji
- Biomedical Omics Research Group, Korea Basic Science Institute, Cheongju, Ochang-eup, 28119, Republic of Korea
| | - Hyun Joo An
- Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, 34134, Republic of Korea
| | - Jin Young Kim
- Biomedical Omics Research Group, Korea Basic Science Institute, Cheongju, Ochang-eup, 28119, Republic of Korea
| | - Jong Shin Yoo
- Biomedical Omics Research Group, Korea Basic Science Institute, Cheongju, Ochang-eup, 28119, Republic of Korea
- Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, 34134, Republic of Korea
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Ioannou GN, Green P, Lowy E, Mun EJ, Berry K. Differences in hepatocellular carcinoma risk, predictors and trends over time according to etiology of cirrhosis. PLoS One 2018; 13:e0204412. [PMID: 30260995 PMCID: PMC6160079 DOI: 10.1371/journal.pone.0204412] [Citation(s) in RCA: 66] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2018] [Accepted: 09/06/2018] [Indexed: 12/15/2022] Open
Abstract
Background and aims Hepatocellular carcinoma (HCC) risk is high in cirrhosis. We sought to describe differences in HCC risk, predictors and trends over time according to etiology of cirrhosis. Methods We identified 116,404 patients with cirrhosis diagnosed between 2001–2014 in the VA healthcare system and determined incident HCC cases occurring from the date of cirrhosis diagnosis until 01/31/2017. Patients were divided by cirrhosis etiology into hepatitis C virus (HCV, n = 52,671), alcoholic liver disease (ALD, n = 35,730), nonalcoholic fatty liver disease (NAFLD, n = 17,354), or OTHER (n = 10,649). Results During a mean follow-up of 4.3 years, 10,042 new HCC cases were diagnosed. Patients with HCV had >3 times higher incidence of HCC (3.3 per 100 patient-years) than patients with ALD (0.86/100 patient-years), NAFLD (0.90/100 patient-years) or OTHER (1.0/100 patient-years), an association that persisted after adjusting for baseline characteristics. HCC incidence was 1.6 times higher in patients with cirrhosis diagnosed in 2008–2014 (2.47/100 patient-years) than in 2001–2007 (1.55/100 patient-years). Independent predictors of HCC among all cirrhosis etiologies included: age, male sex, Hispanic ethnicity, high serum alpha fetoprotein, alkaline phosphatase and AST/√ALT ratio and low serum albumin and platelet count. Diabetes was associated with HCC in ALD-cirrhosis and NAFLD-cirrhosis, and BMI in ALD-cirrhosis. Conclusions HCC risk is 3 times greater in cirrhotic patients with HCV than ALD or NAFLD. HCC risk continues to increase over time in analyses extending to 2017 in cirrhosis of all etiologies. Multiple readily available risk factors for HCC were identified that were influenced by cirrhosis etiology and could be used to develop HCC risk estimation models.
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Affiliation(s)
- George N. Ioannou
- Division of Gastroenterology, Veterans Affairs Puget Sound Healthcare System and University of Washington, Seattle, Washington, United States of America
- Department of Medicine, Veterans Affairs Puget Sound Healthcare System and University of Washington, Seattle, Washington, United States of America
- Health Services Research and Development, Veterans Affairs Puget Sound Healthcare System, Seattle, Washington, United States of America
- * E-mail:
| | - Pamela Green
- Health Services Research and Development, Veterans Affairs Puget Sound Healthcare System, Seattle, Washington, United States of America
| | - Elliott Lowy
- Health Services Research and Development, Veterans Affairs Puget Sound Healthcare System, Seattle, Washington, United States of America
| | - Elijah J. Mun
- Department of Internal Medicine, University of Washington, Seattle, Washington, United States of America
| | - Kristin Berry
- Health Services Research and Development, Veterans Affairs Puget Sound Healthcare System, Seattle, Washington, United States of America
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Xiao L, Liu Q, Zhao W, Pang H, Zeng Q, Chen Y, Zhao J, Mei Q, He X. Chemoembolisation with polyvinyl alcohol for advanced hepatocellular carcinoma with portal vein tumour thrombosis and arterioportal shunts: efficacy and prognostic factors. Clin Radiol 2018; 73:1056.e17-1056.e22. [PMID: 30224186 DOI: 10.1016/j.crad.2018.08.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Accepted: 08/03/2018] [Indexed: 01/14/2023]
Abstract
AIM To evaluate the efficacy and to identify prognostic factors of polyvinyl alcohol (PVA) chemoembolisation for treating advanced hepatocellular carcinoma (HCC) with portal vein (PV) tumour thrombosis (PVTT) and arterioportal shunts. MATERIALS AND METHODS The clinical data of 145 advanced HCC patients with PVTT and arterioportal shunts were collected. The patients were divided into two groups: group A, with main PV invasion, (n=56) and group B, with PV branch invasion, (n=89). Based on arterioportal shunt types, different particle sizes of PVA were used for chemoembolisation. The overall survival (OS), time to progression (TTP), and postoperative complications were analysed retrospectively. RESULTS The median OS of all patients was 10.1 months. The median OS of group A and group B was 8.2 and 12.5 months, respectively (χ2=6.03, p=0.01). The overall 6-, 12-, and 18-month survival rates of groups A and B were 63.8%, 24.9%, and 6.3%, and 78.1%, 55.2%, and 23.7%, respectively. After embolisation, there were two cases of acute liver failure and three cases of upper gastrointestinal bleeding. Cox multivariate survival analysis revealed that main PVTT (HR [hazard ratio]=1.75, p=0.01), Child-Pugh B class (HR=1.99, p=0.003) and tumour burden ≥50% (HR=3.25, p<0.001) were independent risk factors. A dose of oxaliplatin >100 mg (HR=0.48, p<0.001) was an independent protection factor. CONCLUSION Treatment of advanced HCC with PVTT and arterioportal shunts by PVA chemoembolisation is safe and effective. The patients achieved a better prognosis with the dose of oxaliplatin >100 mg, while main PVTT, Child-Pugh B class, and tumour burden ≥50% were poor prognostic indicators.
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Affiliation(s)
- L Xiao
- Department of Interventional Radiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Q Liu
- Department of Tumor and Vascular Interventional Radiology, Affiliated Zhongshan Hospital of Xiamen University, Xiamen, Fujian Province 361004, China
| | - W Zhao
- Department of Interventional Radiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - H Pang
- Department of Interventional Radiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Q Zeng
- Department of Interventional Radiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Y Chen
- Department of Interventional Radiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - J Zhao
- Department of Interventional Radiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Q Mei
- Department of Interventional Radiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - X He
- Department of Interventional Radiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
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Abbastabar M, Sarfi M, Golestani A, Khalili E. lncRNA involvement in hepatocellular carcinoma metastasis and prognosis. EXCLI JOURNAL 2018; 17:900-913. [PMID: 30564069 PMCID: PMC6295623 DOI: 10.17179/excli2018-1541] [Citation(s) in RCA: 70] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Accepted: 08/20/2018] [Indexed: 12/15/2022]
Abstract
Eukaryotic lncRNAs are RNA molecules defined to be greater than 200 bp in length that are not translated to a protein and operate through several mechanisms, including participating in chromatin remodeling and methylation, influencing the integrity and stability of proteins and complexes, or acting as a sponge for miRNA inhibition. A number of recent studies have concentrated on the relationship between long non-coding RNAs (lncRNAs) and cancer. Hepatocellular carcinoma (HCC) is the most prevalent histological type of liver tumors, accounting for about 80 % of the cases worldwide. Lack of proper molecular markers for diagnosis of HCC and treatment evaluation is a significant problem. Dysregulated expression of HCC-related lncRNAs such as MEG-3, MALAT1, HULC, HOTAIR, and H19 have been identified and closely related with tumorigenesis, metastasis, prognosis and diagnosis. In this review, we summarized recent highlighted functions and molecular mechanisms of the most extensively studied lncRNAs in the pathophysiology of hepatocellular carcinoma and their potential for serving as probable therapeutic targets.
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Affiliation(s)
- Maryam Abbastabar
- Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, I.R. Iran
| | - Mohammad Sarfi
- Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, I.R. Iran
| | - Abolfazl Golestani
- Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, I.R. Iran
| | - Ehsan Khalili
- Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, I.R. Iran
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