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Rodgers SK, Fetzer DT, Seow JH, McGillen K, Burrowes DP, Fung C, Udare AS, Wilson SR, Kamaya A. Optimizing US for HCC surveillance. Abdom Radiol (NY) 2025; 50:2453-2463. [PMID: 39585379 PMCID: PMC12069441 DOI: 10.1007/s00261-024-04631-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Revised: 10/02/2024] [Accepted: 10/04/2024] [Indexed: 11/26/2024]
Abstract
Ultrasound is the primary imaging modality used for surveillance of patients at risk for HCC. In 2017, the American College of Radiology Liver Imaging Reporting and Data Systems (ACR LI-RADS) introduced US LI-RADS to standardize the performance, interpretation, and reporting of US for HCC surveillance, with the algorithm recently updated as LI-RADS US Surveillance v2024. The American Association for the Study of Liver Diseases (AASLD) recommends reporting both the examination-level LI-RADS US Category as well as the US Visualization Score. The US Category conveys the overall findings of the exam and primarily determines follow up recommendations. The US Visualization Score conveys the expected sensitivity of the test and stratifies patients into appropriate surveillance pathways. One of the goals of routine surveillance is the detection of HCC at an early, potentially curable stage. Therefore, optimizing US technique is of critical importance. Increasing North American and worldwide utilization of LI-RADS US Surveillance, which includes technical recommendations, through education and outreach will undoubtedly benefit patients undergoing US HCC surveillance.
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Affiliation(s)
| | - David T Fetzer
- The University of Texas Southwestern Medical Center, Dallas, USA
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Rhee H, Kim MJ, Kim DY, An C, Kang W, Han K, Roh YH, Han KH, Ahn SH, Choi JY, Park JY, Chung YE, Kim SU, Kim BK, Lee S, Lee HW, Lee JS. Noncontrast Magnetic Resonance Imaging vs Ultrasonography for Hepatocellular Carcinoma Surveillance: A Randomized, Single-Center Trial. Gastroenterology 2025; 168:1170-1177.e12. [PMID: 39855314 DOI: 10.1053/j.gastro.2024.12.035] [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: 04/02/2024] [Revised: 12/19/2024] [Accepted: 12/26/2024] [Indexed: 01/27/2025]
Abstract
BACKGROUND & AIMS This study aimed to compare ultrasonography (US) and noncontrast magnetic resonance imaging (MRI) in the surveillance of hepatic malignancy. METHODS We conducted a randomized, nonblinded trial at a single center in South Korea. Eligible individuals were aged 20 to 70 years with liver cirrhosis, Child-Pugh class A, and no history of liver cancer or other recent malignancy. Participants were randomized 1:1 to receive up to 10 semiannual surveillance using US or noncontrast MRI with serum alpha-fetoprotein testing. The primary endpoints were the detection rates of Barcelona Clinic Liver Cancer (BCLC) stage 0 or A tumors, stage distribution at initial diagnosis, and false-positive referral rates. RESULTS From June 2015 to November 2017, 416 patients were screened, and 414 were enrolled and assigned to the US (n = 207) or MRI (n = 207) group. In total, 23 participants in the US group and 25 in the MRI group were diagnosed with liver cancer by November 2022. The detection rates of BCLC stage 0 or A tumors were not different between the US and MRI groups (7% [95% confidence interval (CI), 4%-11%] vs 12% [8%-17%]). BCLC stage 0 tumors were more frequently detected in the MRI group than in the US group (8% vs 2%). The MRI group had earlier BCLC stage (P = .014) and lower false-positive referral rate (0.7% [95% CI, 0.4%-1.2%] vs 3.1% [2.3%-4.1%], P < .001) compared with the US group. CONCLUSIONS Noncontrast MRI is a better alternative to US for the surveillance of cirrhotic patients offering earlier stage at initial diagnosis and lower false-positive referral rate. (ClincalTrials.gov, Number: NCT02514434.).
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Affiliation(s)
- Hyungjin Rhee
- Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Myeong-Jin Kim
- Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
| | - Do Young Kim
- Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
| | - Chansik An
- Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Wonseok Kang
- Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Kyunghwa Han
- Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Yun Ho Roh
- Biostatistics Collaboration Unit, Medical Research Center, Yonsei University College of Medicine, Seoul, South Korea
| | - Kwang-Hyub Han
- Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Jin-Young Choi
- Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Jun Yong Park
- Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Yong Eun Chung
- Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Seung Up Kim
- Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Sunyoung Lee
- Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Hye Won Lee
- Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Jae Seung Lee
- Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
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Seif El Dahan K, Yokoo T, Daher D, Davenport MS, Fetzer DT, Mendiratta-Lala M, Rich NE, Yang E, Parikh ND, Singal AG. Multicenter evaluation of abbreviated MRI and ultrasound for detecting early-stage hepatocellular carcinoma. JHEP Rep 2025; 7:101357. [PMID: 40321196 PMCID: PMC12048809 DOI: 10.1016/j.jhepr.2025.101357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Revised: 02/06/2025] [Accepted: 02/10/2025] [Indexed: 05/08/2025] Open
Abstract
Background & aims Abbreviated MRI (AMRI) has been proposed as an alternative to ultrasound for hepatocellular carcinoma (HCC) surveillance; however, comparative data for AMRI and ultrasound are needed. Thus, we evaluated the sensitivity and specificity of dynamic contrast-enhanced (DCE)-AMRI and ultrasound for early-stage HCC detection in patients with cirrhosis. Methods We conducted a multicenter retrospective case-control study among patients with cirrhosis (cases with early-stage HCC as per Milan Criteria; controls without HCC) who underwent an ultrasound and a DCE-MRI within a 6-month period between 2012 and 2019. HCC diagnosis was confirmed by imaging alone in 85% and by histopathology in 15% of patients. Dynamic AMRI examinations were simulated from the full MRI by selecting relevant sequences. Independent, blinded interpretations of ultrasounds and AMRI results were performed using Liver Imaging Reporting and Data System algorithms. Ultrasounds were considered positive if US-3 observations were detected. AMRI was considered positive if LR-4, LR-5, or LR-M were detected. Per-patient sensitivity and specificity for early-stage HCC detection were estimated, and cross-modality differences were tested. Results We included 216 cases and 432 controls. Patient-level sensitivity and specificity of AMRI were significantly higher compared with ultrasound: 80.1% (95% CI 76.1-83.6) vs. 71.1% (95% CI 66.6-75.2), p <0.001, and 91.9% (95% CI 89.9-93.5) vs. 72.3% (95% CI 69.3-75.2), p <0.001, respectively. AMRI sensitivity was significantly higher compared with ultrasound among patients with Child-Pugh B cirrhosis (80.8% vs. 57.4%, p <0.001) but not among those with Child-Pugh A (84.7% vs. 78.6%, p = 0.07) or Child-Pugh C cirrhosis (52.6% vs. 68.4%, p = 0.18). Conclusions Dynamic AMRI may be more sensitive and specific for early-stage HCC detection in patients with cirrhosis compared with ultrasound, although its relative benefit might be smaller in patients with Child-Pugh A cirrhosis. Larger direct comparative data sets are needed, particularly among patients with Child-Pugh C cirrhosis who may benefit from alternative surveillance strategies. Impact and implications Abbreviated MRI (AMRI) is increasingly recognized as an alternative to ultrasound for hepatocellular carcinoma (HCC) surveillance. However, existing data are limited by single-center samples, spectrum bias, and lack of comparative data for AMRI vs. ultrasound. We found that AMRI had significantly higher per-patient sensitivity and specificity compared with ultrasound for the detection of early-stage HCC, although its relative benefit might be smaller in patients with Child-Pugh A cirrhosis, and both modalities underperformed in patients with Child-Pugh C cirrhosis. If sufficiently validated, AMRI could be adopted into practice guidelines for HCC surveillance and serve as a preferred alternative in select subgroups of patients.
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Affiliation(s)
- Karim Seif El Dahan
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA
| | - Takeshi Yokoo
- Department of Radiology, UT Southwestern Medical Center, Dallas, TX, USA
| | - Darine Daher
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA
| | - Matthew S. Davenport
- Department of Radiology, University of Michigan, Ann Arbor, MI, USA
- Department of Urology, University of Michigan, Ann Arbor, MI, USA
| | - David T. Fetzer
- Department of Radiology, UT Southwestern Medical Center, Dallas, TX, USA
| | | | - Nicole E. Rich
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA
| | - Edward Yang
- Division of Gastroenterology, Kaiser Permanente Medical Group, Riverside, CA, USA
| | - Neehar D. Parikh
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Amit G. Singal
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA
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Heald J, Fetzer DT, Rodgers S, Jain V, Fung A, Liu X, Wilson S, Kamaya A, Marks RM. Patient centered HCC surveillance - complementary roles of ultrasound and CT/MRI. Abdom Radiol (NY) 2025; 50:2088-2096. [PMID: 39527256 PMCID: PMC11991968 DOI: 10.1007/s00261-024-04678-x] [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: 08/28/2024] [Revised: 10/31/2024] [Accepted: 11/02/2024] [Indexed: 11/16/2024]
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide and is the fastest growing cause of cancer death in the United States (U.S.) In the U.S., current national clinical practice guidelines from the 2023 American Association for the Study of Liver Diseases (AASLD) Practice Guidance and the recently updated Liver Imaging Reporting & Data Systems (LI-RADS) Ultrasound (US) Surveillance v2024 core recommend semi-annual serum α-fetoprotein and US screening of patients deemed to be high risk for developing HCC. In this article, we will explore the transition to a patient-centered approach to HCC surveillance, including the role of the new LI-RADS US Surveillance v2024 core and the use of visualization score for determining ultrasound quality, the known risk factors for poor US image quality, and the potential options for alternative surveillance strategies when US may not be a viable option for certain patients, including multiphasic computed tomography (CT), magnetic resonance imaging (MRI), and several abbreviated MRI protocols.
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Affiliation(s)
- Jason Heald
- Loma Linda University Medical Center, Loma Linda, USA
| | - David T Fetzer
- The University of Texas Southwestern Medical Center, Dallas, USA
| | | | - Vaibhav Jain
- University of Massachusetts Chan Medical School, Worcester, USA
| | - Alice Fung
- Oregon Health & Science University, Portland, USA
| | - Xiaoyang Liu
- University Medical Imaging Toronto, University Health Network, University of Toronto, Toronto, Canada
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Seif El Dahan K, Yokoo T, Mendiratta-Lala M, Fetzer D, Davenport M, Daher D, Rich NE, Yang E, Parikh ND, Singal AG. Exam quality of ultrasound and dynamic contrast-enhanced abbreviated MRI and impact on early-stage HCC detection. Abdom Radiol (NY) 2025; 50:2097-2109. [PMID: 39542949 DOI: 10.1007/s00261-024-04674-1] [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: 08/24/2024] [Revised: 10/31/2024] [Accepted: 11/02/2024] [Indexed: 11/17/2024]
Abstract
PURPOSE MRI is a potential alternative to ultrasound for hepatocellular carcinoma (HCC) detection. We evaluated the impact of ultrasound and dynamic abbreviated MRI (AMRI) exam quality on early-stage HCC detection. METHODS We conducted a multicenter case-control study among patients with cirrhosis (cases with early-stage HCC per Milan Criteria; controls without HCC) who underwent both a liver ultrasound and dynamic contrast-enhanced (DCE) AMRI within 6 months in 2012-2019. Two radiologists performed independent, blinded interpretations of both exams for HCC detection and scored exam quality as no/mild, moderate, or severe limitations. Associations between exam quality, patient characteristics, and HCC detection were assessed by odds ratios (OR). RESULTS Of 216 cases and 432 controls, severe limitations were reported in 7% and 8% of ultrasounds and DCE-AMRIs, respectively. Severe limitations at ultrasound were associated with obesity (OR 2.08, 95%CI [1.32-3.32]) and metabolic dysfunction-associated steatotic liver disease (MASLD) (OR 1.98 [1.12-3.44]) but not for DCE-AMRI. Decompensated cirrhosis (Child-Pugh C) was associated with severe limitations for both ultrasound (OR 2.54 [1.37-4.58]) and DCE-AMRI (OR 3.96 [2.36-6.58]). Compared to exams with no/mild limitations, exams with severe limitations had lower sensitivity for ultrasound (79.6% vs. 21.7%, P < 0.001) and AMRI (86.1% vs. 50.0%, P = 0.001). In patients in whom ultrasound was severely limited, DCE-AMRI had significantly higher odds of early-stage HCC detection than ultrasound (OR 8.23 [1.25-54.02]). CONCLUSIONS HCC detection by DCE-AMRI may be preferred in patients with severe limitations at ultrasound due to obesity and MASLD. Both modalities remain limited for patients with decompensated cirrhosis, for whom alternative strategies may be needed.
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Affiliation(s)
| | - Takeshi Yokoo
- The University of Texas Southwestern Medical Center, Dallas, USA
| | | | - David Fetzer
- The University of Texas Southwestern Medical Center, Dallas, USA
| | | | - Darine Daher
- The University of Texas Southwestern Medical Center, Dallas, USA
| | - Nicole E Rich
- The University of Texas Southwestern Medical Center, Dallas, USA
| | - Edward Yang
- The University of Texas Southwestern Medical Center, Dallas, USA
| | | | - Amit G Singal
- The University of Texas Southwestern Medical Center, Dallas, USA.
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Grimm LJ, Kruse DE, Tailor TD, Johnson KS, Allen BC, Ryser MD. Current Challenges in Imaging-Based Cancer Screening, From the AJR Special Series on Screening. AJR Am J Roentgenol 2025. [PMID: 40266702 DOI: 10.2214/ajr.25.32808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/25/2025]
Abstract
The early detection of cancer confers many significant benefits for patients, primarily by enabling less invasive and more effective treatments and thus lowering disease mortality. Radiology is integral to early cancer detection, playing either a primary or complementary role in screening programs. Imaging-based screening is often performed in conjunction with other screening tests and may involve multiple modalities depending on patient demographics and cancer type. When developing a screening program for cancer early detection, both its potential benefits and harms need to be assessed. These harms, although specific to the modality and cancer, often include overdiagnosis, overtreatment, and false-positive examinations. As radiology technology improves and new tools become available, the ratios of risk to harm of imaging-based screening will shift, and screening recommendations will need to adapt accordingly. Radiologists must be major partners in the development and execution of screening guidelines to ensure the highest quality of care for their patients. This review discusses the major challenges of cancer screening programs and guidelines, exploring sources of evidence as well as harms of overdiagnosis and overtreatment. The article focuses on the most common cancer types that incorporate imaging-based screening including lung cancer, breast cancer, colon cancer, prostate cancer, and hepatocellcular carcinoma.
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Xie DL, Fan JH, Fan CJ, Gao YH, Cheng JP. A randomized, controlled trial of oral sulfate solution versus polyethylene glycol for bowel preparation for colonoscopy. BMC Gastroenterol 2025; 25:292. [PMID: 40269724 PMCID: PMC12020202 DOI: 10.1186/s12876-025-03885-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Accepted: 04/11/2025] [Indexed: 04/25/2025] Open
Abstract
BACKGROUND The quality of colonoscopy is significantly influenced by the effectiveness of bowel preparation. In this study, we aimed to evaluate the efficacy, safety, and tolerability of bowel cleansing between a new oral sulfate solution (OSS) and standard polyethylene glycol electrolyte powder (PEG). METHODS This single center, randomized, superiority study recruited 679 outpatients who were assigned to either the new OSS group (Group A) or standard PEG group (Group B). The quality of bowel cleansing was evaluated using the Boston Bowel Preparation Scale (BBPS) and compared between the two groups. Furthermore, data pertaining to the duration of bowel preparation, patient tolerability, and the occurrence of adverse events were also analyzed. RESULTS According to BBPS scores, group A demonstrated significantly higher bowel preparation cleanliness than group B. Additionally, group A achieved superior bowel cleansing, as evidenced by a greater proportion of patients with BBPS scores ≥ 8 compared to group B (75.3% vs. 55.2%, P < 0.05). No severe adverse events were reported during examinations in either group. CONCLUSIONS The magnesium sulfate, sodium sulfate, and potassium sulfate concentrated oral solution is a novel, safe, and effective bowel preparation for colonoscopy. TRIAL REGISTRATION This study was registered in the Chinese Clinical Trial Registry on 20/02/2024 (clinical trial registration number: ChiCTR2400081004).
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Affiliation(s)
- Dong-Ling Xie
- Department of Gastroenterology and Oncology, Civil Aviation General Hospital, No. 76 Chaoyang Road, Chaoyang District, Beijing, 100123, China
| | - Jin-Hui Fan
- Civil Aviation Medicine Center, Civil Aviation Administration of China, Beijing, China
| | - Chan-Juan Fan
- Department of Gastroenterology and Oncology, Civil Aviation General Hospital, No. 76 Chaoyang Road, Chaoyang District, Beijing, 100123, China
| | - Ying-Hui Gao
- Department of Gastroenterology and Oncology, Civil Aviation General Hospital, No. 76 Chaoyang Road, Chaoyang District, Beijing, 100123, China
| | - Jian-Ping Cheng
- Department of Gastroenterology and Oncology, Civil Aviation General Hospital, No. 76 Chaoyang Road, Chaoyang District, Beijing, 100123, China.
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Liu Z, Shan D, Han X. GALAD's Impact on HCC Detection: Insights and Future Considerations. Gastroenterology 2025:S0016-5085(25)00629-8. [PMID: 40220969 DOI: 10.1053/j.gastro.2024.09.052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Accepted: 09/18/2024] [Indexed: 04/14/2025]
Affiliation(s)
- Zaoqu Liu
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Dan Shan
- Department of Biobehavioral Sciences, Columbia University, New York, New York
| | - Xinwei Han
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
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Lockhart ME. Editorial Comment: Updated LI-RADS Ultrasound Surveillance Version 2024 Detects More Hepatocellular Carcinomas Than Version 2017 in Patients With Cirrhosis. AJR Am J Roentgenol 2025; 224:e2532695. [PMID: 39878412 DOI: 10.2214/ajr.25.32695] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2025]
Affiliation(s)
- Mark E Lockhart
- Department of Radiology, University of Alabama at Birmingham, JTN 344, 619 19th St S, Birmingham, AL 35249
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Heo S, Kim SY, Lee SJ, Lee SS, Byun JH, Won HJ, Shin YM, Choi SH, Sirlin CB. LI-RADS Ultrasound Surveillance Version 2024: Comparison With Version 2017 for Hepatocellular Carcinoma Detection and Risk Factors for Visualization Score C. AJR Am J Roentgenol 2025; 224:e2432433. [PMID: 39840963 DOI: 10.2214/ajr.24.32433] [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: 01/23/2025]
Abstract
BACKGROUND. The LI-RADS Ultrasound Surveillance algorithm was updated in 2024, incorporating α-fetoprotein (AFP) and a visualization score of VIS-C into management recommendations after nonpositive results. OBJECTIVE. The purpose of this study was to compare the diagnostic performance of LI-RADS Ultrasound Surveillance version 2017 (v2017) and version 2024 (v2024) for the detection of hepatocellular carcinoma (HCC) in at-risk patients and to identify predictors of VIS-C on follow-up surveillance examinations. METHODS. This retrospective analysis included 407 patients (230 men and 177 women; median age, 56 years) with cirrhosis who underwent rounds of semiannual surveillance ultrasound as part of a prospective trial from November 2011 to August 2014. Two radiologists independently assigned ultrasound categories to round 1 examinations and visualization scores to round 1 and round 2 examinations; a third radiologist adjudicated disagreements. The AFP level was considered positive if elevated or increasing from preenrollment values, per v2024 criteria. The reference standard for HCC was positive biopsy or an LR-5 observation on MRI. Diagnostic performance was compared between v2017 and v2024. Logistic regression analyses were performed to identify predictors of a round 2 VIS-C result, with attention given to risk factors for VIS-C described in v2024. RESULTS. HCC was diagnosed in 28 patients (6.9%). LI-RADS Ultrasound Surveillance v2024, in comparison with v2017, showed greater sensitivity for reader 1 (64.3% vs 42.9%, p = .03) and reader 2 (64.3% vs 39.3%, p = .02) and lower specificity for reader 1 (82.1% vs 92.6%, p < .001) and reader 2 (82.3% vs 92.9%, p < .001). All seven patients with HCC detected by v2024 but not v2017 by means of consensus assessments had increasing AFP; two also had elevated AFP. Among 299 patients who underwent round 2 ultrasound after negative round 1 v2024 surveillance results, the only independent predictor of a round 2 VIS-C result was a round 1 VIS-C result (adjusted OR = 21.04 [95% CI, 10.84-40.83], p < .001). For 88 of these patients with round 1 VIS-C, no v2024 risk factor showed a significant univariable association with repeat VIS-C. CONCLUSION. Compared with v2017, LI-RADS Ultrasound Surveillance v2024 had higher sensitivity but lower specificity for HCC detection, which was primarily related to increasing, rather than elevated, AFP. The only independent predictor of VIS-C on subsequent ultrasound was the initial VIS-C result. CLINICAL IMPACT. The findings support the use of LI-RADS Ultrasound Surveillance v2024 to improve HCC detection in at-risk patients.
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Affiliation(s)
- Subin Heo
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil Songpa-gu, 05505 Seoul, Republic of Korea
| | - So Yeon Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil Songpa-gu, 05505 Seoul, Republic of Korea
| | - So Jung Lee
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil Songpa-gu, 05505 Seoul, Republic of Korea
| | - Seung Soo Lee
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil Songpa-gu, 05505 Seoul, Republic of Korea
| | - Jae Ho Byun
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil Songpa-gu, 05505 Seoul, Republic of Korea
| | - Hyung Jin Won
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil Songpa-gu, 05505 Seoul, Republic of Korea
| | - Yong Moon Shin
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil Songpa-gu, 05505 Seoul, Republic of Korea
| | - Sang Hyun Choi
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil Songpa-gu, 05505 Seoul, Republic of Korea
| | - Claude B Sirlin
- Department of Radiology, Liver Imaging Group, UC San Diego, San Diego, CA
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Yang HK, Lee S, Lee MY, Kim MJ. Effectiveness of noncontrast-abbreviated magnetic resonance imaging in a real-world hepatocellular carcinoma surveillance. Eur Radiol 2025:10.1007/s00330-025-11517-0. [PMID: 40111496 DOI: 10.1007/s00330-025-11517-0] [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: 10/16/2024] [Revised: 01/16/2025] [Accepted: 02/17/2025] [Indexed: 03/22/2025]
Abstract
OBJECTIVES Noncontrast-abbreviated magnetic resonance imaging (NC-AMRI) is emerging as a promising alternative to ultrasound (US) for surveillance of hepatocellular carcinoma (HCC) in at-risk patients. We aimed to assess the effectiveness of NC-AMRI in a real-world surveillance population, and to evaluate the appropriateness of NC-AMRI in selected patients with inadequate prior US. MATERIALS AND METHODS This retrospective study included Child-Pugh class A or B adults with chronic hepatitis B or cirrhosis from any cause who underwent NC-AMRI between December 2018 and August 2022. Early- and very early-stage detection, receipt of curative treatment, and false referral were evaluated. Subgroup analysis was performed for patients with inadequate prior US examinations. Descriptive statistics were used. RESULTS Among the 1853 patients (mean age, 58.8 years; 1045 males), 68 HCCs developed in 61 (61/1853, 3.3%, 95% confidence interval: 2.5-4.2) patients. The proportions of early- and very early-stage detection were 95.1% (58/61, 72.2-100.0) and 70.5% (43/61, 51.0-95.0); receipt of curative treatment, 67.2% (41/61, 48.2-91.2); and proportion of false referral, 12.9% (9/70, 5.9-24.4). Among the 375 patients with inadequate prior US, the proportions of early- and very early-stage detection were 94.7% (18/19, 56.2-100.0) and 57.9% (11/19, 28.9-100.0); receipt of curative treatment, 52.6% (10/19, 25.2-96.8); and proportion of false referrals, 17.4% (4/23, 4.7-44.5). CONCLUSION NC-AMRI may be an effective HCC surveillance modality given the results related to early- and very early-stage detection, receipt of curative treatment, and false referral. NC-AMRI can be an alternative HCC surveillance strategy, especially for patients with inadequate prior US examinations. KEY POINTS Question There is insufficient evidence to support the use of noncontrast-abbreviated MRI as an effective surveillance tool in large real-life populations under surveillance. Findings Using noncontrast-abbreviated MRI, most patients who developed HCCs during surveillance were diagnosed at an early stage, with an acceptable false referral rate of 12.9%. Clinical relevance Noncontrast-abbreviated MRI is an effective HCC surveillance modality, especially for patients with inadequate prior ultrasound examinations.
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Affiliation(s)
- Hyun Kyung Yang
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Sunyoung Lee
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea.
| | - Min Young Lee
- Office of Research Affairs/University Industry Foundation, Yonsei University, Seoul, Republic of Korea
| | - Myeong-Jin Kim
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
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12
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Fassio E, Colombato L, Gualano G, Perez S, Puga-Tejada M, Landeira G. Hepatocellular Carcinoma After HCV Eradication with Direct-Acting Antivirals: A Reappraisal Based on New Parameters to Assess the Persistence of Risk. Cancers (Basel) 2025; 17:1018. [PMID: 40149352 PMCID: PMC11940336 DOI: 10.3390/cancers17061018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2025] [Revised: 03/12/2025] [Accepted: 03/16/2025] [Indexed: 03/29/2025] Open
Abstract
Approximately 95% of patients with chronic hepatitis C achieve viral eradication through direct-acting antiviral (DAA) treatment. Ensuing clinical benefits include halting liver fibrosis, thereby reducing the need for liver transplantation, and decreasing both liver-related and overall mortality. It is well established that, although ameliorated, the risk of developing hepatocellular carcinoma (HCC) persists, particularly among patients with pre-treatment advanced fibrosis/cirrhosis. Current guidelines recommend indefinite HCC surveillance in these patients. However, a recent Markov model evaluation shows that HCC surveillance is cost-effective only for patients with cirrhosis but not so for those with F3 fibrosis, a finding which points out the need to better define the risk of HCC in hepatitis C patients after cure and further characterize pre- and post-treatment factors that might affect the incidence of HCC in this setting. We reviewed the literature analyzing this aspect. Here we summarize the main findings: male gender and older age are independent predictors of increased risk of post-cure HCC development. Moreover, non-invasive tests for hepatic fibrosis, namely FIB4, APRI, and liver stiffness, measured before and after treatment and their post-therapy change, contribute to better stratifying the risk of HCC occurrence. Furthermore, low serum albumin, as well as an AFP above 7 ng/mL prior to and after DAA therapy, also constitute independent predictors of HCC development. Considering these findings, we propose to classify patients with HCV viral eradication and advanced fibrosis/cirrhosis into groups of low, medium, or high risk of HCC and to adopt adequate surveillance strategies for each group, including protocols for abbreviated magnetic resonance imaging (MRI) for those at the highest risk.
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Affiliation(s)
- Eduardo Fassio
- Liver Section, Gastroenterology Service, Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires 1684, Argentina; (S.P.); (G.L.)
| | - Luis Colombato
- Hospital Británico de Buenos Aires, Buenos Aires 1280, Argentina;
| | - Gisela Gualano
- Hospital Regional Dr. Ramón Carrillo, Santiago del Estero 4200, Argentina;
| | - Soledad Perez
- Liver Section, Gastroenterology Service, Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires 1684, Argentina; (S.P.); (G.L.)
| | - Miguel Puga-Tejada
- Instituto Ecuatoriano de Enfermedades Digestivas, Guayaquil 090505, Ecuador;
| | - Graciela Landeira
- Liver Section, Gastroenterology Service, Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires 1684, Argentina; (S.P.); (G.L.)
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13
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Lee DH. Recent advances and issues in imaging modalities for hepatocellular carcinoma surveillance. JOURNAL OF LIVER CANCER 2025; 25:31-40. [PMID: 40007309 PMCID: PMC12010830 DOI: 10.17998/jlc.2025.02.16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/28/2024] [Revised: 02/05/2025] [Accepted: 02/16/2025] [Indexed: 02/27/2025]
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. Early detection via surveillance plays a crucial role in enabling curative treatment and improving survival rates. Since the initial randomized controlled trial, biannual ultrasound (US) has been established as the standard surveillance method because of its accessibility, safety, and low cost. However, US has some limitations, including operator dependency, suboptimal sensitivity for early-stage HCC, and challenges such as a limited sonic window that may result in inadequate examination. Alternative imaging modalities, including contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI), have demonstrated higher sensitivity for detecting very early-stage HCC. Recent advancements, such as low-dose CT with deep learning-based reconstruction, have enhanced the safety and feasibility of CT-based surveillance by reducing radiation exposure and amount of contrast media. MRI, particularly with gadoxetic acid or abbreviated protocols, offers superior tissue contrast and sensitivity, although its accessibility and cost remain challenges. Tailored surveillance strategies based on individual risk profiles and integration of advanced imaging technologies have the potential to enhance the detection performance and cost-effectiveness. This review highlights the recent developments in imaging technologies for HCC surveillance, focusing on their respective strengths and limitations.
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Affiliation(s)
- Dong Ho Lee
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
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14
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Arvind A, Redmon K, Singal AG. Persisting challenges in the early detection of hepatocellular carcinoma. Expert Rev Anticancer Ther 2025:1-12. [PMID: 39943795 DOI: 10.1080/14737140.2025.2467184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Accepted: 02/11/2025] [Indexed: 02/25/2025]
Abstract
INTRODUCTION Prognosis in patients with HCC is largely determined by stage at diagnosis, highlighting the importance of effective early detection strategies. HCC surveillance is associated with increased early detection and reduced HCC-related mortality and is currently recommended in patients with cirrhosis or chronic HBV infection. AREAS COVERED We performed a targeted literature review to identify limitations of current HCC surveillance practices and strategies for improvement. EXPERT OPINION Semi-annual ultrasound continues as the cornerstone modality for HCC surveillance but has limited sensitivity for detecting early-stage HCC, particularly in patients with obesity and non-viral etiologies. Although sensitivity for early-stage HCC can be improved by using ultrasound with alpha fetoprotein, this strategy misses over one-third of HCC at an early stage. Emerging imaging and biomarker-based surveillance strategies currently remain in varying stages of validation and are not yet ready for routine use in practice. The cost-effectiveness of surveillance in patients with non-cirrhotic liver disease related to hepatitis C or metabolic dysfunction-associated steatotic liver disease continues to be debated, although subgroups with advanced fibrosis may warrant surveillance. Finally, the effectiveness of surveillance is diminished by underuse in clinical practice, particularly in racial minority and low-income groups, highlighting a need for interventions to increase utilization.
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Affiliation(s)
- Ashwini Arvind
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA
| | - Kennedy Redmon
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA
| | - Amit G Singal
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA
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15
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Fadlallah H, El Masri D, Bahmad HF, Abou-Kheir W, El Masri J. Update on the Complications and Management of Liver Cirrhosis. Med Sci (Basel) 2025; 13:13. [PMID: 39982238 PMCID: PMC11843904 DOI: 10.3390/medsci13010013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2025] [Revised: 02/01/2025] [Accepted: 02/02/2025] [Indexed: 02/22/2025] Open
Abstract
Liver cirrhosis represents the advanced pathological stage of chronic liver disease, characterized by the progressive destruction and regeneration of the hepatic parenchyma over years, culminating in fibrosis and disruption of the vascular architecture. As a leading global cause of morbidity and mortality, it continues to affect millions worldwide, imposing a substantial burden on healthcare systems. Alcoholic/nonalcoholic fatty liver disease and chronic viral hepatitis infection, hepatitis C (HCV) in particular, remain leading causes of cirrhosis. Despite significant advances in understanding the pathogenesis of cirrhosis, its management is still complex due to the multifaceted complications, including ascites, hepatic encephalopathy, variceal bleeding, and hepatocellular carcinoma, all of which severely compromise the patient outcomes and quality of life. This review aims at filling a critical gap by providing a comprehensive summary of the latest evidence on the complications and management of liver cirrhosis. Evidence-based therapies targeting both the etiologies and complications of cirrhosis are essential for improving outcomes. While liver transplantation is considered a definitive cure, advancements in pharmacological therapies offer promising avenues for halting and potentially reversing disease progression. This review summarizes the latest management strategies for cirrhosis and its associated complications, emphasizing the importance of early intervention and novel therapeutic options for improving outcomes and quality of life in affected individuals.
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Affiliation(s)
- Hiba Fadlallah
- Department of Anatomy, Cell Biology, and Physiological Sciences, American University of Beirut, Beirut 1107-2020, Lebanon; (H.F.); (J.E.M.)
| | - Diala El Masri
- Faculty of Medicine, University of Balamand, Al-Kurah, Tripoli P.O. Box 100, Lebanon;
| | - Hisham F. Bahmad
- Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA;
| | - Wassim Abou-Kheir
- Department of Anatomy, Cell Biology, and Physiological Sciences, American University of Beirut, Beirut 1107-2020, Lebanon; (H.F.); (J.E.M.)
| | - Jad El Masri
- Department of Anatomy, Cell Biology, and Physiological Sciences, American University of Beirut, Beirut 1107-2020, Lebanon; (H.F.); (J.E.M.)
- Faculty of Medical Sciences, Lebanese University, Beirut 1107-2020, Lebanon
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16
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Sangro B, Argemi J, Ronot M, Paradis V, Meyer T, Mazzaferro V, Jepsen P, Golfieri R, Galle P, Dawson L, Reig M. EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma. J Hepatol 2025; 82:315-374. [PMID: 39690085 DOI: 10.1016/j.jhep.2024.08.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 08/29/2024] [Indexed: 12/19/2024]
Abstract
Liver cancer is the third leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) accounting for approximately 90% of primary liver cancers. Advances in diagnostic and therapeutic tools, along with improved understanding of their application, are transforming patient treatment. Integrating these innovations into clinical practice presents challenges and necessitates guidance. These clinical practice guidelines offer updated advice for managing patients with HCC and provide a comprehensive review of pertinent data. Key updates from the 2018 EASL guidelines include personalised surveillance based on individual risk assessment and the use of new tools, standardisation of liver imaging procedures and diagnostic criteria, use of minimally invasive surgery in complex cases together with updates on the integrated role of liver transplantation, transitions between surgical, locoregional, and systemic therapies, the role of radiation therapies, and the use of combination immunotherapies at various stages of disease. Above all, there is an absolute need for a multiparametric assessment of individual risks and benefits, considering the patient's perspective, by a multidisciplinary team encompassing various specialties.
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17
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Marsh TL, Parikh ND, Roberts LR, Schwartz ME, Nguyen MH, Befeler A, Page-Lester S, Tayob N, Srivastava S, Rinaudo JA, Singal AG, Reddy KR, Marrero JA. A Phase 3 Biomarker Validation of GALAD for the Detection of Hepatocellular Carcinoma in Cirrhosis. Gastroenterology 2025; 168:316-326.e6. [PMID: 39293548 PMCID: PMC12120501 DOI: 10.1053/j.gastro.2024.09.008] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Revised: 08/12/2024] [Accepted: 09/02/2024] [Indexed: 09/20/2024]
Abstract
BACKGROUND & AIMS Better surveillance tests for hepatocellular carcinoma (HCC) are needed. The GALAD score (gender, age, α-fetoprotein [AFP] L3, AFP, and des-γ carboxyprothrombin) has been shown to have excellent sensitivity and specificity for HCC in phase 2 studies. We performed a phase 3 biomarker validation study to compare GALAD with AFP in detecting HCC. METHODS This is a prospective study of patients with cirrhosis enrolled at 7 centers. Surveillance for HCC was performed every 6 months at each site, and HCC diagnosis was confirmed per American Association for the Study of Liver Diseases guidelines. Blood for biomarker research was obtained at each follow-up visit and stored in a biorepository. Measurements of AFP, AFP-L3, and des-γ carboxyprothrombin) were performed in a FujiFilm laboratory by staff blinded to clinical data. The performance of GALAD in detecting HCC was retrospectively evaluated within 12 months before the clinical diagnosis. All analyses were conducted by an unblinded statistician in the Early Detection Research Network data management and coordinating center. RESULTS A total of 1,558 patients with cirrhosis were enrolled and followed for a median of 2.2 years. A total of 109 patients developed HCC (76 very early or early stage), with an annual incident rate of 2.4%. The areas under the curve for AFP and GALAD within 12 months before HCC were 0.66 and 0.78 (P < .001), respectively. Using a cutoff for GALAD of -1.36, the specificity was 82%, and the sensitivity at 12 months before HCC diagnosis was 62%. For comparison, performance of AFP at 82% specificity showed 41% sensitivity at 12 months before HCC diagnosis (P = .001). CONCLUSIONS GALAD score, compared to AFP, improves the detection of HCC within 12 months before the actual diagnosis.
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Affiliation(s)
- Tracey L Marsh
- Biostatistics Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Neehar D Parikh
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan
| | - Lewis R Roberts
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota
| | - Myron E Schwartz
- Recanati/Miller Transplant Institute, Mount Sinai Medical Center, New York, New York
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology and Department of Epidemiology and Population Health, Stanford University, Palo Alto, California
| | - Alex Befeler
- Division of Gastroenterology, Saint Louis University, St. Louis, Missouri
| | - Stephanie Page-Lester
- Biostatistics Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Nabihah Tayob
- Department of Data Science, Dana Farber Cancer Institute, Boston, Massachusetts
| | - Sudhir Srivastava
- Cancer Biomarkers Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland
| | - Jo Ann Rinaudo
- Cancer Biomarkers Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland
| | - Amit G Singal
- Division of Digestive and Liver Disease, University of Texas Southwestern, Dallas, Texas
| | - K Rajender Reddy
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Jorge A Marrero
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania.
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18
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Wang C, Zhu SC, Liang JH. Value of Abbreviated Magnetic Resonance Sequence in Hepatocellular Carcinoma Screening: A Systematic Review and Meta-analysis. Acad Radiol 2025:S1076-6332(24)00993-0. [PMID: 39757062 DOI: 10.1016/j.acra.2024.12.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 12/08/2024] [Accepted: 12/11/2024] [Indexed: 01/07/2025]
Abstract
RATIONALE AND OBJECTIVES To systematically review the diagnostic efficacy of abbreviated magnetic resonance imaging sequence (AMRI) screening for hepatocellular carcinoma (HCC). MATERIALS AND METHODS Medline (via PubMed), EMbase, The Cochrane Library, Web of Science, CNKI, WanFang Data, and VIP databases were electronically searched to collect studies on the diagnostic efficacy of AMRI screening for HCC from inception to August 10th, 2024. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies using the Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2), then, the meta-analysis with a bivariate mixed-effects regression model was performed by using Stata 14.0 software. RESULTS A total of 19 studies involving 3914 participants were included which published from 2013 to 2024. The results of meta-analysis showed that pooled sensitivity and specificity of AMRI for HCC were 0.85 (95% confidence interval (CI) 0.83 to 0.87) and 0.93 (95%CI 0.91 to 0.94). Subgroup analysis showed that the pooled sensitivity and specificity of NC (Non-Contrast) AMRI and HBP (Hepatobiliary Phase Images) AMRI were 0.84 (95%CI 0.80 to 0.87), 0.92 (95%CI 0.89 to 0.94) and 0.88 (95%CI 0.84 to 0.91), 0.93 (95%CI 0.91 to 0.95), respectively. And the T2 (T2 Weighted Imaging)+DWI (Diffusion Weighted Imaging)+HBP protocol in HBP AMRI had the highest diagnostic efficacy, its pooled sensitivity, specificity and the area under the summary receiver operating characteristic (SROC) curve (AUC) were 0.88 (95%CI 0.83 to 0.92), 0.93 (95%CI 0.91 to 0.95), and 0.96 (95%CI 0.94 to 0.98), respectively. CONCLUSION Current evidence suggests that the AMRI protocols demonstrated potential for HCC detection, which employing a limited number of sequences with the aim of achieving a diagnostic performance comparable to conventional complete contrast-enhanced MRI (CE-MRI). Among them, T2+DWI+HBP protocol shows the relatively highest diagnostic efficiency, which is perhaps the most promising application in clinical practice. Nevertheless, the results still should be carefully interpreted in the relevant context of medical history, physical examination, and biochemical indicators.
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Affiliation(s)
- Cong Wang
- Department of Medical Imaging, Henan Provincial People's Hospital, Zhengzhou, PR China (C.W., S.C.Z.).
| | - Shao-Cheng Zhu
- Department of Medical Imaging, Henan Provincial People's Hospital, Zhengzhou, PR China (C.W., S.C.Z.)
| | - Jing-Hong Liang
- Department of Maternal and Child Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, PR China (J.H.L.); Department of Social medicine, School of Public Health, Medical College of Soochow University, Suzhou, Jiangsu 215123, PR China (J.H.L.); Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou, Jiangsu 215123, PR China (J.H.L.)
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19
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Nguyen T, Vennatt J, Downs L, Surabhi V, Stanietzky N. Advanced Imaging of Hepatocellular Carcinoma: A Review of Current and Novel Techniques. J Gastrointest Cancer 2024; 55:1469-1484. [PMID: 39158837 DOI: 10.1007/s12029-024-01094-8] [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] [Accepted: 07/16/2024] [Indexed: 08/20/2024]
Abstract
Hepatocellular carcinoma (HCC) is the most common primary carcinoma arising from the liver. Although HCC can arise de novo, the vast majority of cases develop in the setting of chronic liver disease. Hepatocarcinogenesis follows a well-studied process during which chronic inflammation and cellular damage precipitate cellular and genetic aberrations, with subsequent propagation of precancerous and cancerous lesions. Surveillance of individuals at high risk of HCC, early diagnosis, and individualized treatment are keys to reducing the mortality associated with this disease. Radiological imaging plays a critical role in the diagnosis and management of these patients. HCC is a unique cancer in that it can be diagnosed with confidence by imaging that meets all radiologic criteria, obviating the risks associated with tissue sampling. This article discusses conventional and emerging imaging techniques for the evaluation of HCC.
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Affiliation(s)
- Trinh Nguyen
- Department of Abdominal Imaging, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Jaijo Vennatt
- Department of Diagnostic Radiology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, 77030, USA
| | - Lincoln Downs
- Department of Abdominal Imaging, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Venkateswar Surabhi
- Department of Abdominal Imaging, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Nir Stanietzky
- Department of Abdominal Imaging, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
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20
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Fiduzi FIF, Willemssen FEJA, de Braak CV, de Lussanet de la Sablonière QG, IJzermans JNM, Bos D, de Man RA, Dwarkasing RS. Evaluation of Hepatocellular Carcinoma Surveillance with Contrast-enhanced MRI in a High-Risk Western European Cohort. Curr Probl Diagn Radiol 2024; 53:709-716. [PMID: 39003123 DOI: 10.1067/j.cpradiol.2024.07.001] [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: 03/01/2024] [Revised: 06/04/2024] [Accepted: 07/08/2024] [Indexed: 07/15/2024]
Abstract
AIM To investigate the utilization of MRI using a MRI liver protocol with extracellular contrast-enhanced series for hepatocellular carcinoma (HCC) surveillance in high-risk patients. METHODS Consecutive high-risk patients of a western European cohort who underwent repeated liver MRI for HCC screening were included. Lesions were registered according to the Liver Reporting & Data System (LIRADS) 2018. HCC was staged as very early stage HCC (BCLC stage 0) and more advanced stages of HCC (BCLC stage A-D). Differences in time interval between MRI's for BCLC stage 0 and stage A-D were calculated with the Mann-Whitney U test. The HCC cumulative incidence at one-, three- and five years was calculated with the Kaplan Meier estimator. RESULTS From 2010 to 2019 a total of 240 patients were included (71% male; median age: 57 years; IQR: 50-64 years) with 1350 MRI's. Most patients (83 %) had cirrhosis with hepatitis C as the most common underlying cause. Patients underwent on average four MRI's (IQR: 3-7). Forty-two patients (17.5%) developed HCC (52 HCC lesions: 43 LIRADS-5, eight LIRADS-4, and one LIRADS-TIV). Eighteen patients (43%) had BCLC stage 0 HCC with a significant shorter screening time interval (10 months; IQR: 6-21) compared to patients with BCLC stage A-D (21 months; IQR: 10-32) (p = 0.03). Thirty seven percent of patients with a LIRADS-3 lesion (n=43) showed HCC development within twelve months (median: 7.4 months). One, three- and five-year HCC cumulative incidence in cirrhotic patients was 1%, 10% and 17%, respectively. CONCLUSION High-risk patients who underwent surveillance with contrast-enhanced MRI developed HCC in 17.5 % during a follow up period of over 4 years median. Very early stage HCC was seen in compensated cirrhosis after a median time interval of 10 months. Later stages of HCC were related to prolonged screening time interval (median 21 months).
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Affiliation(s)
- Federico I F Fiduzi
- Department of Radiology & Nuclear Medicine, Erasmus Medical Center, Dr. Molewaterplein 40, 3015GD, Rotterdam, The Netherlands
| | - François E J A Willemssen
- Department of Radiology & Nuclear Medicine, Erasmus Medical Center, Dr. Molewaterplein 40, 3015GD, Rotterdam, The Netherlands
| | - Céline van de Braak
- Department of Radiology & Nuclear Medicine, Erasmus Medical Center, Dr. Molewaterplein 40, 3015GD, Rotterdam, The Netherlands
| | | | - Jan N M IJzermans
- Department of Surgery, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Daniel Bos
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Robert A de Man
- Department of Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Roy S Dwarkasing
- Department of Radiology & Nuclear Medicine, Erasmus Medical Center, Dr. Molewaterplein 40, 3015GD, Rotterdam, The Netherlands.
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21
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Singal AG, Ng M, Kulkarni A. Advancing Surveillance Strategies for Hepatocellular Carcinoma: A New Era of Efficacy and Precision. J Clin Exp Hepatol 2024; 14:101448. [PMID: 38946864 PMCID: PMC11214318 DOI: 10.1016/j.jceh.2024.101448] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Accepted: 05/13/2024] [Indexed: 07/02/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the few cancers with a 5-year survival that has remained below 20%; however, prognosis differs by tumor stage at diagnosis. Curative treatment options among patients with early-stage HCC afford a median survival of 5-10 years. Accordingly, international society guidelines recommend semi-annual HCC surveillance in at-risk patients, including those with cirrhosis or high-risk chronic hepatitis B infection. Surveillance is associated with increased early-stage HCC detection and curative treatments, leading to reduced HCC-related mortality. Abdominal ultrasound has been the cornerstone for HCC surveillance for the past two decades, but recent data have highlighted its suboptimal sensitivity for early-stage HCC detection, particularly in patients with obesity and those with non-viral etiologies of liver disease. The combination of ultrasound plus alpha fetoprotein (AFP) has higher sensitivity for early-stage HCC detection than ultrasound alone, although the combination still misses over one-third of HCC at an early stage. Emerging imaging and blood-based biomarker strategies have promising data in biomarker phase 2 (case-control) and phase 3 (cohort) studies. Beyond ultrasound, Magnetic resonance imaging (MRI) is the best-studied imaging strategy, with superior sensitivity and specificity compared to ultrasound in a cohort study. Abbreviated MRI protocols have been proposed to address concerns about MRI radiological capacity, costs, and patient acceptance. Of biomarker strategies, GALAD (a panel including gender, age, AFP, AFP-L3, and DCP) is the best validated, with promising sensitivity for early-stage HCC detection in a national multi-center cohort study. Liquid biopsy biomarkers, including methylated DNA markers, have also shown promising accuracy in case-control studies. Abbreviated MRI and GALAD are now entering prospective trials that examine clinical outcomes such as early-stage HCC detection and screening-related harms, which are essential data to understand for adoption in clinical practice. As additional surveillance strategies become available, it will allow an era of precision surveillance in which optimal surveillance modalities are tailored to individual patient risk and expected test performance.
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Affiliation(s)
- Amit G. Singal
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA
| | - Michelle Ng
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA
| | - Anand Kulkarni
- Department of Hepatology, AIG Hospitals, Hyderabad, India
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22
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Zhai Y, Hai D, Zeng L, Lin C, Tan X, Mo Z, Tao Q, Li W, Xu X, Zhao Q, Shuai J, Pan J. Artificial intelligence-based evaluation of prognosis in cirrhosis. J Transl Med 2024; 22:933. [PMID: 39402630 PMCID: PMC11475999 DOI: 10.1186/s12967-024-05726-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Accepted: 10/02/2024] [Indexed: 10/19/2024] Open
Abstract
Cirrhosis represents a significant global health challenge, characterized by high morbidity and mortality rates that severely impact human health. Timely and precise prognostic assessments of liver cirrhosis are crucial for improving patient outcomes and reducing mortality rates as they enable physicians to identify high-risk patients and implement early interventions. This paper features a thorough literature review on the prognostic assessment of liver cirrhosis, aiming to summarize and delineate the present status and constraints associated with the application of traditional prognostic tools in clinical settings. Among these tools, the Child-Pugh and Model for End-Stage Liver Disease (MELD) scoring systems are predominantly utilized. However, their accuracy varies significantly. These systems are generally suitable for broad assessments but lack condition-specific applicability and fail to capture the risks associated with dynamic changes in patient conditions. Future research in this field is poised for deep exploration into the integration of artificial intelligence (AI) with routine clinical and multi-omics data in patients with cirrhosis. The goal is to transition from static, unimodal assessment models to dynamic, multimodal frameworks. Such advancements will not only improve the precision of prognostic tools but also facilitate personalized medicine approaches, potentially revolutionizing clinical outcomes.
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Affiliation(s)
- Yinping Zhai
- Department of Gastroenterology Nursing Unit, Ward 192, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
| | - Darong Hai
- The School of Nursing, Wenzhou Medical University, Wenzhou, 325000, China
| | - Li Zeng
- The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, 325000, China
| | - Chenyan Lin
- The School of Nursing, Wenzhou Medical University, Wenzhou, 325000, China
| | - Xinru Tan
- The First School of Medicine, School of Information and Engineering, Wenzhou Medical University, Wenzhou, 325000, China
| | - Zefei Mo
- School of Biomedical Engineering, School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, 325000, China
| | - Qijia Tao
- The School of Nursing, Wenzhou Medical University, Wenzhou, 325000, China
| | - Wenhui Li
- The School of Nursing, Wenzhou Medical University, Wenzhou, 325000, China
| | - Xiaowei Xu
- Department of Gastroenterology Nursing Unit, Ward 192, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
| | - Qi Zhao
- School of Computer Science and Software Engineering, University of Science and Technology Liaoning, Anshan, 114051, China.
- Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, 325000, China.
| | - Jianwei Shuai
- Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, 325000, China.
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision, and Brain Health), Wenzhou, 325000, China.
| | - Jingye Pan
- Department of Big Data in Health Science, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
- Key Laboratory of Intelligent Treatment and Life Support for Critical Diseases of Zhejiang Province, Wenzhou, 325000, China.
- Zhejiang Engineering Research Center for Hospital Emergency and Process Digitization, Wenzhou, 325000, China.
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Teng W, Wang HW, Lin SM, On Behalf of Diagnosis Group and Systemic Therapy Group of TLCA. Management Consensus Guidelines for Hepatocellular Carcinoma: 2023 Update on Surveillance, Diagnosis, Systemic Treatment, and Posttreatment Monitoring by the Taiwan Liver Cancer Association and the Gastroenterological Society of Taiwan. Liver Cancer 2024; 13:468-486. [PMID: 39435274 PMCID: PMC11493393 DOI: 10.1159/000537686] [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: 08/03/2023] [Accepted: 02/02/2024] [Indexed: 10/08/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is the leading cause of cancer-related mortality in Taiwan. The Taiwan Liver Cancer Association and the Gastroenterological Society of Taiwan established HCC management consensus guidelines in 2016 and updated them in 2023. Current recommendations focus on addressing critical issues in HCC management, including surveillance, diagnosis, systemic treatment, and posttreatment monitoring. For surveillance and diagnosis, we updated the guidelines to include the role of protein induced by vitamin K absence or antagonist II (PIVKA-II) and gadoxetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) in detecting HCCs. For systemic treatment, the updated guidelines summarize the multiple choices available for targeted therapy, immune checkpoint inhibitors, and a combination of both, especially for those carcinomas refractory to or unsuitable for transarterial chemoembolization. We have added a new section, posttreatment monitoring, that describes the important roles of PIVKA-II and EOB-MRI after HCC therapy, including surgery, locoregional therapy, and systemic treatment. Through this update of the management consensus guidelines, patients with HCC may benefit from optimal diagnosis, therapeutic modalities, and posttreatment monitoring.
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Affiliation(s)
- Wei Teng
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Hung-Wei Wang
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
| | - Shi-Ming Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - On Behalf of Diagnosis Group and Systemic Therapy Group of TLCA
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
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Argenziano ME, Kim MN, Montori M, Di Bucchianico A, Balducci D, Ahn SH, Svegliati Baroni G. Epidemiology, pathophysiology and clinical aspects of Hepatocellular Carcinoma in MAFLD patients. Hepatol Int 2024; 18:922-940. [PMID: 39012579 DOI: 10.1007/s12072-024-10692-4] [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: 02/03/2024] [Accepted: 04/24/2024] [Indexed: 07/17/2024]
Abstract
Hepatocellular carcinoma (HCC) is undergoing a transformative shift, with metabolic-associated fatty liver disease (MAFLD) emerging as a dominant etiology. Diagnostic criteria for MAFLD involve hepatic steatosis and metabolic dysregulation. Globally, MAFLD prevalence stands at 38.77%, significantly linked to the escalating rates of obesity. Epidemiological data indicate a dynamic shift in the major etiologies of hepatocellular carcinoma (HCC), transitioning from viral to metabolic liver diseases. Besides the degree of liver fibrosis, several modifiable lifestyle risk factors, such as type 2 diabetes, obesity, alcohol use, smoking, and HBV, HCV infection contribute to the pathogenesis of HCC. Moreover gut microbiota and genetic variants may contribute to HCC development.The pathophysiological link between MAFLD and HCC involves metabolic dysregulation, impairing glucose and lipid metabolism, inflammation and oxidative stress. Silent presentation poses challenges in early MAFLD-HCC diagnosis. Imaging, biopsy, and AI-assisted techniques aid diagnosis, while HCC surveillance in non-cirrhotic MAFLD patients remains debated.ITA.LI.CA. group proposes a survival-based algorithm for treatment based on Barcelona clinic liver cancer (BCLC) algorithm. Liver resection, transplantation, ablation, and locoregional therapies are applied based on the disease stage. Systemic treatments is promising, with initial immunotherapy results indicating a less favorable response in MAFLD-related HCC.Adopting lifestyle interventions and chemopreventive measures with medications, including aspirin, metformin, and statins, constitute promising approaches for the primary prevention of HCC.Prognosis is influenced by multiple factors, with MAFLD-HCC associated with prolonged survival. Emerging diagnostic biomarkers and epigenomic markers, show promising results for early HCC detection in the MAFLD population.
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Affiliation(s)
- Maria Eva Argenziano
- Clinic of Gastroenterology, Hepatology, and Emergency Digestive Endoscopy, Università Politecnica Delle Marche, 60126,, Ancona, Italy
- Faculty of Medicine and Health Sciences, University of Ghent, Ghent, Belgium
| | - Mi Na Kim
- Department of Internal Medicine, Yonsei University College of Medicine, 50 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Michele Montori
- Clinic of Gastroenterology, Hepatology, and Emergency Digestive Endoscopy, Università Politecnica Delle Marche, 60126,, Ancona, Italy
| | - Alessandro Di Bucchianico
- Clinic of Gastroenterology, Hepatology, and Emergency Digestive Endoscopy, Università Politecnica Delle Marche, 60126,, Ancona, Italy
| | - Daniele Balducci
- Clinic of Gastroenterology, Hepatology, and Emergency Digestive Endoscopy, Università Politecnica Delle Marche, 60126,, Ancona, Italy
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, 50 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea.
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea.
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea.
| | - Gianluca Svegliati Baroni
- Liver Disease and Transplant Unit, Obesity Center, Azienda Ospedaliero-Universitaria Delle Marche, Polytechnic University of Marche, Ancona, Italy
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Singal A. Emerging Strategies for Hepatocellular Carcinoma Surveillance. Gastroenterol Hepatol (N Y) 2024; 20:560-562. [PMID: 39483999 PMCID: PMC11523088] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2024]
Affiliation(s)
- Amit Singal
- Willis C. Maddrey Distinguished Chair in Liver Disease Professor of Internal Medicine Medical Director of the Liver Tumor Program Chief of Hepatology UT Southwestern Medical Center Dallas, Texas
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26
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Maung ST, Tanpowpong N, Satja M, Treeprasertsuk S, Chaiteerakij R. MRI for hepatocellular carcinoma and the role of abbreviated MRI for surveillance of hepatocellular carcinoma. J Gastroenterol Hepatol 2024; 39:1969-1981. [PMID: 38899804 DOI: 10.1111/jgh.16643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Revised: 05/16/2024] [Accepted: 05/24/2024] [Indexed: 06/21/2024]
Abstract
INTRODUCTION Hepatocellular carcinoma (HCC) constitutes the majority of liver cancers and significantly impacts global cancer mortality. While ultrasound (US) with or without alpha-fetoprotein is the mainstay for HCC surveillance, its limitations highlight the necessity for more effective surveillance tools. Therefore, this review explores evolving imaging modalities and abbreviated magnetic resonance imaging (MRI) (AMRI) protocols as promising alternatives, addressing challenges in HCC surveillance. AREAS COVERED This comprehensive review delves into the evaluation and challenges of HCC surveillance tools, focusing on non-contrast abbreviated MRI (NC-AMRI) and contrast-enhanced abbreviated MRI protocols. It covers the implementation of AMRI for HCC surveillance, patient preferences, adherence, and strategies for optimizing cost-effectiveness. Additionally, the article provides insights into prospects for HCC surveillance by summarizing meta-analyses, prospective studies, and ongoing clinical trials evaluating AMRI protocols. EXPERT OPINION The opinions underscore the transformative impact of AMRI on HCC surveillance, especially in overcoming US limitations. Promising results from NC-AMRI protocols indicate its potential for high-risk patient surveillance, though prospective studies in true surveillance settings are essential for validation. Future research should prioritize risk-stratified AMRI protocols and address cost-effectiveness for broader clinical implementation, alongside comparative analyses with US for optimal surveillance strategies.
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Affiliation(s)
- Soe Thiha Maung
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Ma Har Myaing Hospital, Yangon, Myanmar
| | - Natthaporn Tanpowpong
- Division of Diagnostic Radiology, Department of Radiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Minchanat Satja
- Division of Diagnostic Radiology, Department of Radiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Sombat Treeprasertsuk
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Roongruedee Chaiteerakij
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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Kao SYZ, Sangha K, Fujiwara N, Hoshida Y, Parikh ND, Singal AG. Cost-effectiveness of a precision hepatocellular carcinoma surveillance strategy in patients with cirrhosis. EClinicalMedicine 2024; 75:102755. [PMID: 39234558 PMCID: PMC11372615 DOI: 10.1016/j.eclinm.2024.102755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Revised: 07/09/2024] [Accepted: 07/11/2024] [Indexed: 09/06/2024] Open
Abstract
Background Hepatocellular carcinoma (HCC) surveillance is currently performed using a one-size-fits-all strategy with ultrasound plus AFP (US + AFP). There is increasing interest in risk-stratified and precision surveillance strategies incorporating individual risk and variance in surveillance test performance; however, the cost-effectiveness of these approaches has not been evaluated. Methods We conducted a cost-effectiveness analysis to evaluate four surveillance strategies (no surveillance, universal US + AFP surveillance, risk-stratified surveillance, and precision surveillance) in a simulated cohort of 50-year-old patients with compensated cirrhosis. The most cost-effective strategy was that with the highest incremental cost-effectiveness ratio (ICER) and below the willingness-to-pay (WTP) threshold of $150,000/QALY gained. Model inputs were based on literature review, and costs were derived from the Medicare fee schedule. Findings The precision surveillance strategy demonstrated variation in recommended surveillance test based on HCC risk category and patient factors. US + AFP, risk-stratified, and precision surveillance detected more HCC cases per 100,000 population than no surveillance, with a higher proportion of early-stage cases for precision surveillance (67.6%) than risk-stratified (63.8%), universal ultrasound (63.2%), and no surveillance (38.0%). Compared to no surveillance, precision surveillance was most cost-effective, with an ICER of $104,614/QALY gained, whereas US + AFP and risk-stratified surveillance were both dominated. Compared to US + AFP, risk-stratified surveillance was cost saving and dominated US + AFP, whereas precision surveillance was cost-effective, with an ICER of $98,103/QALY gained. Results were sensitive to survival with early-stage HCC, cost of early-stage HCC treatment, and surveillance utilization. Precision surveillance remained the most cost-effective when WTP thresholds exceeded $110,000/QALY gained. Interpretation A precision surveillance strategy is the most cost-effective method for HCC surveillance. This approach could maximize surveillance benefits in high-risk patients, while minimizing surveillance harms in low-risk individuals. Funding National Cancer Institute (U01 CA230694, R01 CA222900, R01 CA212008, and U24ca086368) and Cancer Prevention Research Institute of Texas (CPRIT) (RP200554).
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Affiliation(s)
| | | | - Naoto Fujiwara
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Yujin Hoshida
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Neehar D. Parikh
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Amit G. Singal
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
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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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Tacke F, Horn P, Wai-Sun Wong V, Ratziu V, Bugianesi E, Francque S, Zelber-Sagi S, Valenti L, Roden M, Schick F, Yki-Järvinen H, Gastaldelli A, Vettor R, Frühbeck G, Dicker D. EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J Hepatol 2024; 81:492-542. [PMID: 38851997 DOI: 10.1016/j.jhep.2024.04.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 04/30/2024] [Indexed: 06/10/2024]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty liver disease (NAFLD), is defined as steatotic liver disease (SLD) in the presence of one or more cardiometabolic risk factor(s) and the absence of harmful alcohol intake. The spectrum of MASLD includes steatosis, metabolic dysfunction-associated steatohepatitis (MASH, previously NASH), fibrosis, cirrhosis and MASH-related hepatocellular carcinoma (HCC). This joint EASL-EASD-EASO guideline provides an update on definitions, prevention, screening, diagnosis and treatment for MASLD. Case-finding strategies for MASLD with liver fibrosis, using non-invasive tests, should be applied in individuals with cardiometabolic risk factors, abnormal liver enzymes, and/or radiological signs of hepatic steatosis, particularly in the presence of type 2 diabetes (T2D) or obesity with additional metabolic risk factor(s). A stepwise approach using blood-based scores (such as FIB-4) and, sequentially, imaging techniques (such as transient elastography) is suitable to rule-out/in advanced fibrosis, which is predictive of liver-related outcomes. In adults with MASLD, lifestyle modification - including weight loss, dietary changes, physical exercise and discouraging alcohol consumption - as well as optimal management of comorbidities - including use of incretin-based therapies (e.g. semaglutide, tirzepatide) for T2D or obesity, if indicated - is advised. Bariatric surgery is also an option in individuals with MASLD and obesity. If locally approved and dependent on the label, adults with non-cirrhotic MASH and significant liver fibrosis (stage ≥2) should be considered for a MASH-targeted treatment with resmetirom, which demonstrated histological effectiveness on steatohepatitis and fibrosis with an acceptable safety and tolerability profile. No MASH-targeted pharmacotherapy can currently be recommended for the cirrhotic stage. Management of MASH-related cirrhosis includes adaptations of metabolic drugs, nutritional counselling, surveillance for portal hypertension and HCC, as well as liver transplantation in decompensated cirrhosis.
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Wang B, Hu S, Teng Y, Chen J, Wang H, Xu Y, Wang K, Xu J, Cheng Y, Gao X. Current advance of nanotechnology in diagnosis and treatment for malignant tumors. Signal Transduct Target Ther 2024; 9:200. [PMID: 39128942 PMCID: PMC11323968 DOI: 10.1038/s41392-024-01889-y] [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: 01/07/2024] [Revised: 05/04/2024] [Accepted: 06/02/2024] [Indexed: 08/13/2024] Open
Abstract
Cancer remains a significant risk to human health. Nanomedicine is a new multidisciplinary field that is garnering a lot of interest and investigation. Nanomedicine shows great potential for cancer diagnosis and treatment. Specifically engineered nanoparticles can be employed as contrast agents in cancer diagnostics to enable high sensitivity and high-resolution tumor detection by imaging examinations. Novel approaches for tumor labeling and detection are also made possible by the use of nanoprobes and nanobiosensors. The achievement of targeted medication delivery in cancer therapy can be accomplished through the rational design and manufacture of nanodrug carriers. Nanoparticles have the capability to effectively transport medications or gene fragments to tumor tissues via passive or active targeting processes, thus enhancing treatment outcomes while minimizing harm to healthy tissues. Simultaneously, nanoparticles can be employed in the context of radiation sensitization and photothermal therapy to enhance the therapeutic efficacy of malignant tumors. This review presents a literature overview and summary of how nanotechnology is used in the diagnosis and treatment of malignant tumors. According to oncological diseases originating from different systems of the body and combining the pathophysiological features of cancers at different sites, we review the most recent developments in nanotechnology applications. Finally, we briefly discuss the prospects and challenges of nanotechnology in cancer.
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Affiliation(s)
- Bilan Wang
- Department of Pharmacy, Evidence-based Pharmacy Center, Children's Medicine Key Laboratory of Sichuan Province, West China Second University Hospital, Sichuan University, Chengdu, 610041, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, 610041, P.R. China
| | - Shiqi Hu
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, 610041, P.R. China
- Department of Gynecology and Obstetrics, Development and Related Diseases of Women and Children Key Laboratory of Sichuan Province, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, 610041, P.R. China
| | - Yan Teng
- Institute of Laboratory Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, P.R. China
| | - Junli Chen
- West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, 610041, China
| | - Haoyuan Wang
- Department of Neurosurgery and Institute of Neurosurgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China
| | - Yezhen Xu
- Department of Neurosurgery and Institute of Neurosurgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China
| | - Kaiyu Wang
- Department of Neurosurgery and Institute of Neurosurgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China
| | - Jianguo Xu
- Department of Neurosurgery and Institute of Neurosurgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China
| | - Yongzhong Cheng
- Department of Neurosurgery and Institute of Neurosurgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.
| | - Xiang Gao
- Department of Neurosurgery and Institute of Neurosurgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.
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Maung ST, Deepan N, Decharatanachart P, Chaiteerakij R. Abbreviated MRI for Hepatocellular Carcinoma Surveillance - A Systematic Review and Meta-analysis. Acad Radiol 2024; 31:3142-3156. [PMID: 38413315 DOI: 10.1016/j.acra.2024.01.028] [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: 12/14/2023] [Revised: 01/18/2024] [Accepted: 01/22/2024] [Indexed: 02/29/2024]
Abstract
BACKGROUND Given the limited sensitivity of ultrasound in hepatocellular carcinoma (HCC) surveillance, this systematic review and meta-analysis were aimed to assess the diagnostic performance of non-contrast abbreviated MRI (NC-aMRI) compared to contrast-enhanced abbreviated MRI (CE-aMRI) for HCC surveillance, offering evidence-based guidance for clinical decision-making. METHODS A comprehensive search was conducted across five databases, identifying studies on aMRI for HCC surveillance. The pooled sensitivity and specificity were estimated using a random effects model. Subgroup analyses and meta-regression were performed by study location, proportion of patients with cirrhosis and HCC, and underlying liver diseases. RESULTS The meta-analysis included 27 studies (2009-2023), distributed between Western (n = 14) and Eastern (n = 13) countries. The pooled sensitivity and specificity (95%CI, I2) were 86% (83-88%, 63%) and 92% (90%-94%, 74%). The NC-aMRI protocols reported in 21 studies exhibited 83% (79-87%, 63%) sensitivity and 91% (88-93%, 67%) specificity, while the 15 studies on CE-aMRI protocols displayed 88% (84-91%, 64%) sensitivity and 94% (90-96%, 78%) specificity, with no statistically significant differences in sensitivity (p = 0.078) or specificity (p = 0.157). Subgroup analysis in NC-aMRI studies showed significant differences in sensitivity for high-prevalent chronic hepatitis B (87% vs. 78%, p = 0.003) and studies done in eastern countries (86% vs. 76%, p = 0.018). Additionally, specificity showed significant differences for high-prevalent chronic hepatitis C (94% vs. 90%, p = 0.009), with meta-regression identifying major sources of study heterogeneity as the inclusion of a majority of patients with chronic hepatitis B (p = 0.008) and the geographic regions where studies were conducted (p = 0.030). CONCLUSION Surveillance aMRI protocols exhibit satisfactory performance for detecting HCC. NC-aMRI may be used effectively for HCC surveillance, especially in chronic hepatitis B prevalent settings.
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Affiliation(s)
- Soe Thiha Maung
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, 1873 Rama IV Road, Patumwan, Bangkok, Thailand; Ma Har Myaing Hospital, Yangon, Myanmar
| | - Natee Deepan
- Division of Academic Affairs, 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, Thai Red Cross Society, 1873 Rama IV Road, Patumwan, Bangkok, Thailand; Center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
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Hui S, Nguyen A, Le S, Dev A, Bell S. Clinical outcomes of hepatocellular carcinoma surveillance in Melbourne, Australia. Intern Med J 2024; 54:1360-1368. [PMID: 38666599 DOI: 10.1111/imj.16405] [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: 10/18/2023] [Accepted: 03/28/2024] [Indexed: 08/20/2024]
Abstract
BACKGROUND Ultrasound surveillance for hepatocellular carcinoma (HCC) may improve early tumour detection but may additionally result in surveillance-related harm through increased evaluation of non-HCC lesions. The incidence of these outcomes has not been reported outside North America. AIMS We aimed to report the outcomes of HCC surveillance with respect to both surveillance-related benefits and harms. METHODS We reviewed all HCC surveillance ultrasounds at a large Victorian tertiary hospital network in 2017 and followed their outcomes until 2021. Surveillance-related benefits were defined as early-stage HCC detection. Surveillance-related harm was defined as contrast imaging, biopsies or surgery performed to evaluate non-HCC liver lesions or false-positive alpha-fetoprotein levels. RESULTS Five hundred and fifty-three patients were included (mean age 54.5 ± 12.3 years, males 67.5%, cirrhosis 50.3%). The most common liver disease aetiology was hepatitis B (53.9%). Over a median of 4.7 years follow-up, early-stage HCC was detected in 3.3% (5.4% in cirrhotic vs 1.1% in non-cirrhotic patients, P < 0.01). 75% of all HCCs were early-stage. Surveillance-related harm occurred in 12.5% (15.5% in cirrhotic vs 9.5% in non-cirrhotic patients, P < 0.04), although most harm was mild (12.1%). In subgroup analysis, the detection of early-stage HCC ranged between 0% (screened outside of guideline criteria and alcoholic cirrhotic patients) and 7.2% (hepatitis C cirrhosis). Harm occurred between 9% (non-cirrhotic hepatitis B) and 20.8% (thrombocytopenia). CONCLUSION In our study, HCC surveillance was associated with early tumour detection, although many patients experienced mild surveillance-related harm. Novel surveillance strategies and pathways are required to improve detection in high-risk patients and minimise harm in low-risk patients.
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Affiliation(s)
- Samuel Hui
- Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, Victoria, Australia
| | - Andrew Nguyen
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, Victoria, Australia
| | - Suong Le
- Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, Victoria, Australia
| | - Anouk Dev
- Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, Victoria, Australia
| | - Sally Bell
- Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, Victoria, Australia
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Vithayathil M, Qurashi M, Vicente PR, Alsafi A, Naik M, Graham A, Khan S, Lewis H, Dhar A, Smith B, Selvapatt N, Manousou P, Possamai L, Izadi H, Lim A, Tait P, Sharma R. Prospective Study of Non-Contrast, Abbreviated MRI for Hepatocellular Carcinoma Surveillance in Patients with Suboptimal Hepatic Visualisation on Ultrasound. Cancers (Basel) 2024; 16:2709. [PMID: 39123437 PMCID: PMC11312001 DOI: 10.3390/cancers16152709] [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: 07/10/2024] [Accepted: 07/26/2024] [Indexed: 08/12/2024] Open
Abstract
BACKGROUND Biannual ultrasound (US) is recommended for hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis. However, US has limited sensitivity for early-stage HCC, particularly in overweight cohorts, where hepatic visualisation is often inadequate. Currently there are no robust imaging surveillance strategies in patients with inadequate US visualisation. We investigated the ability of non-contrast, abbreviated magnetic resonance imaging (aMRI) to adequately visualise the liver for HCC surveillance in patients with previously inadequate US. METHODS Patients undergoing US surveillance, where liver visualisation was inadequate (LI-RADS VIS-B and VIS-C), were prospectively recruited. Patients underwent non-contrast T2-weighted and diffusion-weighted aMRI. The images were reviewed and reported by an expert liver radiologist. Three independent, blinded radiologists assessed the aMRI visualisation quality using a binary score assessing five parameters (parenchymal definition, vascular definition, coverage of the liver, uniformity of liver appearance and signal-to-noise ratio). RESULTS Thirty patients completed the aMRI protocol. The majority (90%) had underlying cirrhosis and were overweight (93.3%), with 50% obese and 20% severely obese. A total of 93.3% of the aMRI scans were of satisfactory quality. Six patients (20%) had hepatic abnormalities detected with aMRI that were not seen on their US: one HCC, one haemangioma and three clinically insignificant lesions. For the aMRI visualisation quality assessment, the coverage of the liver, vascular definition and parenchymal definition were consistently rated to be of sufficient quality by all three radiologists. CONCLUSIONS Non-contrast aMRI provided good visualisation of the liver and detection of abnormalities in patients with inadequate US. aMRI should be further explored in a larger, prospective study as an alternative surveillance strategy in patients with inadequate US.
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Affiliation(s)
- Mathew Vithayathil
- Department of Surgery and Cancer, Imperial College London, London W12 0NN, UK; (M.V.)
| | - Maria Qurashi
- Department of Surgery and Cancer, Imperial College London, London W12 0NN, UK; (M.V.)
| | | | - Ali Alsafi
- Department of Interventional Radiology, Imperial College Healthcare NHS Trust, London W12 0HS, UK
| | - Mitesh Naik
- Department of Nuclear Medicine, Imperial College Healthcare NHS Trust, London W12 0HS, UK;
| | - Alison Graham
- Department of Interventional Radiology, Imperial College Healthcare NHS Trust, London W12 0HS, UK
| | - Shahid Khan
- Department of Hepatology, Imperial College Healthcare NHS Trust, London W12 0HS, UK (A.D.); (N.S.)
| | - Heather Lewis
- Department of Hepatology, Imperial College Healthcare NHS Trust, London W12 0HS, UK (A.D.); (N.S.)
| | - Ameet Dhar
- Department of Hepatology, Imperial College Healthcare NHS Trust, London W12 0HS, UK (A.D.); (N.S.)
| | - Belinda Smith
- Department of Hepatology, Imperial College Healthcare NHS Trust, London W12 0HS, UK (A.D.); (N.S.)
| | - Nowlan Selvapatt
- Department of Hepatology, Imperial College Healthcare NHS Trust, London W12 0HS, UK (A.D.); (N.S.)
| | - Pinelopi Manousou
- Department of Hepatology, Imperial College Healthcare NHS Trust, London W12 0HS, UK (A.D.); (N.S.)
| | - Lucia Possamai
- Department of Hepatology, Imperial College Healthcare NHS Trust, London W12 0HS, UK (A.D.); (N.S.)
| | - Hooshang Izadi
- School of Engineering, Computing and Mathematics, Oxford Brookes University, Oxford OX3 0BP, UK
| | - Adrian Lim
- Department of Radiology, Imperial College Healthcare NHS Trust, London W12 0HS, UK
| | - Paul Tait
- Department of Interventional Radiology, Imperial College Healthcare NHS Trust, London W12 0HS, UK
| | - Rohini Sharma
- Department of Surgery and Cancer, Imperial College London, London W12 0NN, UK; (M.V.)
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EASL-EASD-EASO Clinical Practice Guidelines on the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Obes Facts 2024; 17:374-444. [PMID: 38852583 PMCID: PMC11299976 DOI: 10.1159/000539371] [Citation(s) in RCA: 18] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 05/15/2024] [Indexed: 06/11/2024] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty liver disease (NAFLD), is defined as steatotic liver disease (SLD) in the presence of one or more cardiometabolic risk factor(s) and the absence of harmful alcohol intake. The spectrum of MASLD includes steatosis, metabolic dysfunction-associated steatohepatitis (MASH, previously NASH), fibrosis, cirrhosis and MASH-related hepatocellular carcinoma (HCC). This joint EASL-EASD-EASO guideline provides an update on definitions, prevention, screening, diagnosis and treatment for MASLD. Case-finding strategies for MASLD with liver fibrosis, using non-invasive tests, should be applied in individuals with cardiometabolic risk factors, abnormal liver enzymes, and/or radiological signs of hepatic steatosis, particularly in the presence of type 2 diabetes (T2D) or obesity with additional metabolic risk factor(s). A stepwise approach using blood-based scores (such as FIB-4) and, sequentially, imaging techniques (such as transient elastography) is suitable to rule-out/in advanced fibrosis, which is predictive of liver-related outcomes. In adults with MASLD, lifestyle modification - including weight loss, dietary changes, physical exercise and discouraging alcohol consumption - as well as optimal management of comorbidities - including use of incretin-based therapies (e.g. semaglutide, tirzepatide) for T2D or obesity, if indicated - is advised. Bariatric surgery is also an option in individuals with MASLD and obesity. If locally approved and dependent on the label, adults with non-cirrhotic MASH and significant liver fibrosis (stage ≥2) should be considered for a MASH-targeted treatment with resmetirom, which demonstrated histological effectiveness on steatohepatitis and fibrosis with an acceptable safety and tolerability profile. No MASH-targeted pharmacotherapy can currently be recommended for the cirrhotic stage. Management of MASH-related cirrhosis includes adaptations of metabolic drugs, nutritional counselling, surveillance for portal hypertension and HCC, as well as liver transplantation in decompensated cirrhosis.
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Li X, Liang X, Li Z, Liang J, Qi Z, Zhong L, Geng Z, Liang W, Quan X, Liang C, Liu Z. A novel stratification scheme combined with internal arteries in CT imaging for guiding postoperative adjuvant transarterial chemoembolization in hepatocellular carcinoma: a retrospective cohort study. Int J Surg 2024; 110:2556-2567. [PMID: 38377071 DOI: 10.1097/js9.0000000000001191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Accepted: 01/31/2024] [Indexed: 02/22/2024]
Abstract
BACKGROUND Although postoperative adjuvant transarterial chemoembolization (PA-TACE) improves survival outcomes in a subset of patients with resected hepatocellular carcinoma (HCC), the lack of reliable biomarkers for patient selection remains a significant challenge. The present study aimed to evaluate whether computed tomography imaging can provide more value for predicting benefits from PA-TACE and to establish a new scheme for guiding PA-TACE benefits. METHODS In this retrospective study, patients with HCC who had undergone preoperative contrast-enhanced computed tomography and curative hepatectomy were evaluated. Inverse probability of treatment weight was performed to balance the difference of baseline characteristics. Cox models were used to test the interaction among PA-TACE, imaging features, and pathological indicators. An HCC imaging and pathological classification (HIPC) scheme incorporating these imaging and pathological indicators was established. RESULTS This study included 1488 patients [median age, 52 years (IQR, 45-61 years); 1309 male]. Microvascular invasion (MVI) positive, and diameter >5 cm tumors achieved a higher recurrence-free survival (RFS), and overall survival (OS) benefit, respectively, from PA-TACE than MVI negative, and diameter ≤5 cm tumors. Patients with internal arteries (IA) positive benefited more than those with IA-negative in terms of RFS ( P =0.016) and OS ( P =0.018). PA-TACE achieved significant RFS and OS improvements in HIPC3 (IA present and diameter >5 cm, or two or three tumors) patients but not in HIPC1 (diameter ≤5 cm, MVI negative) and HIPC2 (other single tumor) patients. Our scheme may decrease the number of patients receiving PA-TACE by ~36.5% compared to the previous suggestion. CONCLUSIONS IA can provide more value for predicting the benefit of PA-TACE treatment. The proposed HIPC scheme can be used to stratify patients with and without survival benefits from PA-TACE.
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Affiliation(s)
- Xinming Li
- Department of Radiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University
- Department of Radiology
| | - Xiangjing Liang
- Ultrasound Medical Center, Zhujiang Hospital Southern Medical University
| | - Zhipeng Li
- Department of Radiology, Sun Yat-sen University Cancer Center
| | - Jianye Liang
- Department of Radiology, Sun Yat-sen University Cancer Center
| | | | - Liming Zhong
- School of Biomedical Engineering, Southern Medical University
| | - Zhijun Geng
- Department of Radiology, Sun Yat-sen University Cancer Center
| | | | | | - Changhong Liang
- Department of Radiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University
- Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application, Guangzhou, People's Republic of China
| | - Zaiyi Liu
- Department of Radiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University
- Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application, Guangzhou, People's Republic of China
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Mendiratta-Lala M, Fetzer D, Kamaya A, Parikh ND, Singal AG. The Future Role of Abdominal US in Hepatocellular Carcinoma Surveillance. Radiology 2024; 311:e232624. [PMID: 38742973 PMCID: PMC11140528 DOI: 10.1148/radiol.232624] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Revised: 12/16/2023] [Accepted: 12/26/2023] [Indexed: 05/16/2024]
Abstract
Abdominal US is currently the best-validated surveillance strategy for hepatocellular carcinoma (HCC) in at-risk patients. It is the only modality shown to have completed all five phases of validation and can achieve high sensitivity and specificity for HCC detection, especially when conducted by expert sonographers in high-volume centers. However, US also has limitations, including operator dependency and varying sensitivity in clinical practice. Further, the sensitivity of US for early-stage HCC detection is lower in patients with obesity or nonviral liver disease, increasingly common populations undergoing surveillance. Imaging-based and blood-based surveillance strategies, including abbreviated MRI and biomarker panels, may overcome some limitations of US-based surveillance. Both strategies have promising test performance in phase II and phase III biomarker studies and are undergoing prospective validation. Considering the variation in HCC risk and test performance between patients, there will likely be a shift away from a one-size-fits-all approach and toward precision screening, in which the "best" test is selected based on individual patient characteristics. In this upcoming era of precision HCC screening among patients with cirrhosis, US will likely continue to have an important, albeit reduced, surveillance role.
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Affiliation(s)
| | | | - Aya Kamaya
- From the Departments of Radiology (M.M.L.) and Internal Medicine
(N.D.P.), University of Michigan, Ann Arbor, Mich; Department of Radiology
(D.F.) and Department of Internal Medicine, Division of Digestive and Liver
Diseases (A.G.S.), University of Texas Southwestern Medical Center, 5959 Harry
Hines Blvd, Ste 420, POB 1, Dallas, TX 75390-8887; and Department of Radiology,
Stanford University School of Medicine, Stanford, Calif (A.K.)
| | - Neehar D. Parikh
- From the Departments of Radiology (M.M.L.) and Internal Medicine
(N.D.P.), University of Michigan, Ann Arbor, Mich; Department of Radiology
(D.F.) and Department of Internal Medicine, Division of Digestive and Liver
Diseases (A.G.S.), University of Texas Southwestern Medical Center, 5959 Harry
Hines Blvd, Ste 420, POB 1, Dallas, TX 75390-8887; and Department of Radiology,
Stanford University School of Medicine, Stanford, Calif (A.K.)
| | - Amit G. Singal
- From the Departments of Radiology (M.M.L.) and Internal Medicine
(N.D.P.), University of Michigan, Ann Arbor, Mich; Department of Radiology
(D.F.) and Department of Internal Medicine, Division of Digestive and Liver
Diseases (A.G.S.), University of Texas Southwestern Medical Center, 5959 Harry
Hines Blvd, Ste 420, POB 1, Dallas, TX 75390-8887; and Department of Radiology,
Stanford University School of Medicine, Stanford, Calif (A.K.)
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Fares S, Wehrle CJ, Hong H, Sun K, Jiao C, Zhang M, Gross A, Allkushi E, Uysal M, Kamath S, Ma WW, Modaresi Esfeh J, Linganna MW, Khalil M, Pita A, Kim J, Walsh RM, Miller C, Hashimoto K, Schlegel A, Kwon DCH, Aucejo F. Emerging and Clinically Accepted Biomarkers for Hepatocellular Carcinoma. Cancers (Basel) 2024; 16:1453. [PMID: 38672535 PMCID: PMC11047909 DOI: 10.3390/cancers16081453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 04/03/2024] [Accepted: 04/08/2024] [Indexed: 04/28/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death and the sixth most diagnosed malignancy worldwide. Serum alpha-fetoprotein (AFP) is the traditional, ubiquitous biomarker for HCC. However, there has been an increasing call for the use of multiple biomarkers to optimize care for these patients. AFP, AFP-L3, and prothrombin induced by vitamin K absence II (DCP) have described clinical utility for HCC, but unfortunately, they also have well established and significant limitations. Circulating tumor DNA (ctDNA), genomic glycosylation, and even totally non-invasive salivary metabolomics and/or micro-RNAS demonstrate great promise for early detection and long-term surveillance, but still require large-scale prospective validation to definitively validate their clinical validity. This review aims to provide an update on clinically available and emerging biomarkers for HCC, focusing on their respective clinical strengths and weaknesses.
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Affiliation(s)
- Sami Fares
- Department of Hepato-Pancreato-Biliary & Liver Transplant Surgery, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA; (S.F.); (H.H.); (K.S.); (C.J.); (M.Z.); (A.G.); (E.A.); (M.U.); (M.K.); (A.P.); (J.K.); (R.M.W.); (K.H.); (A.S.); (D.C.H.K.)
| | - Chase J. Wehrle
- Department of Hepato-Pancreato-Biliary & Liver Transplant Surgery, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA; (S.F.); (H.H.); (K.S.); (C.J.); (M.Z.); (A.G.); (E.A.); (M.U.); (M.K.); (A.P.); (J.K.); (R.M.W.); (K.H.); (A.S.); (D.C.H.K.)
| | - Hanna Hong
- Department of Hepato-Pancreato-Biliary & Liver Transplant Surgery, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA; (S.F.); (H.H.); (K.S.); (C.J.); (M.Z.); (A.G.); (E.A.); (M.U.); (M.K.); (A.P.); (J.K.); (R.M.W.); (K.H.); (A.S.); (D.C.H.K.)
| | - Keyue Sun
- Department of Hepato-Pancreato-Biliary & Liver Transplant Surgery, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA; (S.F.); (H.H.); (K.S.); (C.J.); (M.Z.); (A.G.); (E.A.); (M.U.); (M.K.); (A.P.); (J.K.); (R.M.W.); (K.H.); (A.S.); (D.C.H.K.)
| | - Chunbao Jiao
- Department of Hepato-Pancreato-Biliary & Liver Transplant Surgery, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA; (S.F.); (H.H.); (K.S.); (C.J.); (M.Z.); (A.G.); (E.A.); (M.U.); (M.K.); (A.P.); (J.K.); (R.M.W.); (K.H.); (A.S.); (D.C.H.K.)
| | - Mingyi Zhang
- Department of Hepato-Pancreato-Biliary & Liver Transplant Surgery, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA; (S.F.); (H.H.); (K.S.); (C.J.); (M.Z.); (A.G.); (E.A.); (M.U.); (M.K.); (A.P.); (J.K.); (R.M.W.); (K.H.); (A.S.); (D.C.H.K.)
| | - Abby Gross
- Department of Hepato-Pancreato-Biliary & Liver Transplant Surgery, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA; (S.F.); (H.H.); (K.S.); (C.J.); (M.Z.); (A.G.); (E.A.); (M.U.); (M.K.); (A.P.); (J.K.); (R.M.W.); (K.H.); (A.S.); (D.C.H.K.)
| | - Erlind Allkushi
- Department of Hepato-Pancreato-Biliary & Liver Transplant Surgery, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA; (S.F.); (H.H.); (K.S.); (C.J.); (M.Z.); (A.G.); (E.A.); (M.U.); (M.K.); (A.P.); (J.K.); (R.M.W.); (K.H.); (A.S.); (D.C.H.K.)
| | - Melis Uysal
- Department of Hepato-Pancreato-Biliary & Liver Transplant Surgery, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA; (S.F.); (H.H.); (K.S.); (C.J.); (M.Z.); (A.G.); (E.A.); (M.U.); (M.K.); (A.P.); (J.K.); (R.M.W.); (K.H.); (A.S.); (D.C.H.K.)
| | - Suneel Kamath
- Department of Hematology and Oncology, Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA; (S.K.); (W.W.M.)
| | - Wen Wee Ma
- Department of Hematology and Oncology, Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA; (S.K.); (W.W.M.)
| | - Jamak Modaresi Esfeh
- Department of Gastroenterology, Hepatology, and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA; (J.M.E.); (M.W.L.)
| | - Maureen Whitsett Linganna
- Department of Gastroenterology, Hepatology, and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA; (J.M.E.); (M.W.L.)
| | - Mazhar Khalil
- Department of Hepato-Pancreato-Biliary & Liver Transplant Surgery, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA; (S.F.); (H.H.); (K.S.); (C.J.); (M.Z.); (A.G.); (E.A.); (M.U.); (M.K.); (A.P.); (J.K.); (R.M.W.); (K.H.); (A.S.); (D.C.H.K.)
| | - Alejandro Pita
- Department of Hepato-Pancreato-Biliary & Liver Transplant Surgery, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA; (S.F.); (H.H.); (K.S.); (C.J.); (M.Z.); (A.G.); (E.A.); (M.U.); (M.K.); (A.P.); (J.K.); (R.M.W.); (K.H.); (A.S.); (D.C.H.K.)
| | - Jaekeun Kim
- Department of Hepato-Pancreato-Biliary & Liver Transplant Surgery, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA; (S.F.); (H.H.); (K.S.); (C.J.); (M.Z.); (A.G.); (E.A.); (M.U.); (M.K.); (A.P.); (J.K.); (R.M.W.); (K.H.); (A.S.); (D.C.H.K.)
| | - R. Matthew Walsh
- Department of Hepato-Pancreato-Biliary & Liver Transplant Surgery, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA; (S.F.); (H.H.); (K.S.); (C.J.); (M.Z.); (A.G.); (E.A.); (M.U.); (M.K.); (A.P.); (J.K.); (R.M.W.); (K.H.); (A.S.); (D.C.H.K.)
| | - Charles Miller
- Department of Hepato-Pancreato-Biliary & Liver Transplant Surgery, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA; (S.F.); (H.H.); (K.S.); (C.J.); (M.Z.); (A.G.); (E.A.); (M.U.); (M.K.); (A.P.); (J.K.); (R.M.W.); (K.H.); (A.S.); (D.C.H.K.)
| | - Koji Hashimoto
- Department of Hepato-Pancreato-Biliary & Liver Transplant Surgery, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA; (S.F.); (H.H.); (K.S.); (C.J.); (M.Z.); (A.G.); (E.A.); (M.U.); (M.K.); (A.P.); (J.K.); (R.M.W.); (K.H.); (A.S.); (D.C.H.K.)
| | - Andrea Schlegel
- Department of Hepato-Pancreato-Biliary & Liver Transplant Surgery, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA; (S.F.); (H.H.); (K.S.); (C.J.); (M.Z.); (A.G.); (E.A.); (M.U.); (M.K.); (A.P.); (J.K.); (R.M.W.); (K.H.); (A.S.); (D.C.H.K.)
| | - David Choon Hyuck Kwon
- Department of Hepato-Pancreato-Biliary & Liver Transplant Surgery, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA; (S.F.); (H.H.); (K.S.); (C.J.); (M.Z.); (A.G.); (E.A.); (M.U.); (M.K.); (A.P.); (J.K.); (R.M.W.); (K.H.); (A.S.); (D.C.H.K.)
| | - Federico Aucejo
- Department of Hepato-Pancreato-Biliary & Liver Transplant Surgery, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA; (S.F.); (H.H.); (K.S.); (C.J.); (M.Z.); (A.G.); (E.A.); (M.U.); (M.K.); (A.P.); (J.K.); (R.M.W.); (K.H.); (A.S.); (D.C.H.K.)
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P de Jong Y, Jacobson IM. Monitoring for liver cancer post-gene therapy-How much and how often? J Viral Hepat 2024; 31 Suppl 1:35-40. [PMID: 38606953 PMCID: PMC11549964 DOI: 10.1111/jvh.13898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2023] [Accepted: 11/04/2023] [Indexed: 04/13/2024]
Abstract
Hepatocellular carcinoma (HCC) has long been recognized as a complication in people with chronic liver disease, particularly those with cirrhosis. Two gene therapies for haemophilia A and B recently approved in Europe and the US utilize adeno-associated virus (AAV) vectors designed to target hepatocytes. A number of other AAV gene therapies are undergoing clinical investigation for both liver and extrahepatic diseases, many of which likely transduce hepatocytes as well. Although AAV vectors predominantly persist in episomal forms, concerns about insertional mutagenesis have arisen due to findings in pre-clinical models and in a small subset of human HCC cases featuring wild-type AAV integrations in proximity to potential oncogenes. Despite the absence of any causative link between AAV vector therapy and HCC in approved extrahepatic gene therapies or haemophilia gene therapy trials, the package inserts for the recently approved haemophilia gene therapies advise HCC screening in subsets of individuals with additional risk factors. In this review, we discuss HCC risk factors, compare various screening modalities, discuss optimal screening intervals, and consider when to initiate and possibly discontinue screening. At this early point in the evolution of gene therapy, we lack sufficient data to make evidence-based recommendations on HCC screening. While AAV vectors may eventually be shown to be unassociated with risk of HCC, we presently favour a cautious approach that entails regular surveillance until such time as it is hopefully proven to be unnecessary.
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Affiliation(s)
- Ype P de Jong
- Weill Cornell Medical College, Rockefeller University, New York, New York, USA
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Lai YW, Chung CH. Epidemiology of Hepatocellular Carcinoma in Taiwan. Clin Pract 2024; 14:570-578. [PMID: 38666802 PMCID: PMC11048999 DOI: 10.3390/clinpract14020044] [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: 01/22/2024] [Revised: 03/14/2024] [Accepted: 03/19/2024] [Indexed: 04/28/2024] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a major contributor to the world's cancer burden. Understanding the HCC incidence rate in Taiwan is thus an interesting avenue of research. METHODS From an NHI database, those patients who had been newly diagnosed with HCC and who had been listed on a registry in a catastrophic illness dataset during the years 2013-2021 were enrolled in this study. Antineoplastic agent usage and comorbidities were also studied. RESULTS The incidence rate of HCC decreased from 57.77 to 44.95 in 100,000 from 2013 to 2021. The average age of patients with HCC increased from 65.54 years old with a CCI score of 4.98 in 2013 to 67.92 years old with a CCI score of 5.49 in 2021. Among these HCC patients, the patients under antineoplastic agent treatment decreased from 53.47% to 31.41% from 2013 to 2021. The presence of comorbidities in HCC patients was about 55.77-83.01% with mild liver disease and 29.93-37.30% with diabetes (without complications) in the period 2013-2021. CONCLUSIONS The incidence rate of HCC slightly decreased in Taiwan. Due to antineoplastic agent usage decreasing over time, these results may indicate that more early-stage HCC patients detected in recent years were mainly treated with surgeries.
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Affiliation(s)
- Yu-Wei Lai
- General Education Center, University of Taipei, Taipei 104, Taiwan;
- Division of Urology, Taipei City Hospital Renai Branch, Taipei 106, Taiwan
| | - Ching-Hu Chung
- Department of Medicine, Mackay Medical College, New Taipei City 252, Taiwan
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van de Braak C, Willemssen FEJA, de Man RA, van der Lugt A, Uyl-de Groot CA, Bos D, Dwarkasing RS. Non-contrast short MRI surveillance for HCC screening: the study protocol of the SMS-HCC prospective multicenter study. Eur Radiol Exp 2024; 8:29. [PMID: 38467990 PMCID: PMC10928023 DOI: 10.1186/s41747-024-00432-6] [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: 09/22/2023] [Accepted: 01/11/2024] [Indexed: 03/13/2024] Open
Abstract
Hepatocellular carcinoma (HCC) comprises 75 to 85% of all primary liver cancers. Current guidelines recommend a biannual HCC surveillance using ultrasound (US) for high-risk patients. However, due to its low sensitivity for detection of early-stage HCC lesions, there is an urgency for more sensitive surveillance tools. Here, we describe the potential of a short MRI surveillance (SMS) protocol for HCC, including axial T1-weighted in-out phase, fat-saturated T2-weighted, and diffusion-weighted sequences. In this prospective, multicenter, patient cohort study, patients will be recruited from existing HCC surveillance cohorts of six medical centers in The Netherlands. Surveillance patients who undergo biannual US, will be invited for SMS on the same day for 3 years. In case of a suspicious finding on either US or SMS, patients will be invited for a full MRI liver protocol including gadolinium-based contrast agent intravenous injection within 2 weeks. To our knowledge, this will be the first study to perform a head-to-head comparison with a paired US-MRI design. We hypothesize that the sensitivity of SMS for detection of early-stage HCC will be higher than that of US leading to improved survival of surveillance patients through timely HCC diagnosis. Furthermore, we hypothesize that the SMS-HCC protocol will prove cost-effective.Relevance statement The US sensitivity for detecting early-stage HCC has been reported to be less than 50%. We expect that the proposed SMS will detect at least twice as many early-stage HCC lesions and therefore prove to be cost-effective. Key points • The low sensitivity of US necessitates better imaging tools for HCC screening.• This is the first study with a paired US-MRI design.• This design will allow a head-to-head comparison in both diagnostics and patient-acceptance.• We expect that SMS can contribute to a higher survival rate.
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Affiliation(s)
- Céline van de Braak
- Department of Radiology & Nuclear Medicine, Erasmus Medical Center, Dr. Molewaterplein 40, Rotterdam, 3015GD, The Netherlands.
| | - François E J A Willemssen
- Department of Radiology & Nuclear Medicine, Erasmus Medical Center, Dr. Molewaterplein 40, Rotterdam, 3015GD, The Netherlands
| | - Rob A de Man
- Department of Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Aad van der Lugt
- Department of Radiology & Nuclear Medicine, Erasmus Medical Center, Dr. Molewaterplein 40, Rotterdam, 3015GD, The Netherlands
| | - Carin A Uyl-de Groot
- Erasmus School of Health Policy & Management and Institute for Medical Technology Assessment, Erasmus University Rotterdam, Rotterdam, The Netherlands
| | - Daniel Bos
- Department of Radiology & Nuclear Medicine, Erasmus Medical Center, Dr. Molewaterplein 40, Rotterdam, 3015GD, The Netherlands
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Roy S Dwarkasing
- Department of Radiology & Nuclear Medicine, Erasmus Medical Center, Dr. Molewaterplein 40, Rotterdam, 3015GD, The Netherlands.
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Nahon P, Ronot M, Sutter O, Natella PA, Baloul S, Durand-Zaleski I, Audureau E. Study protocol for FASTRAK: a randomised controlled trial evaluating the cost impact and effectiveness of FAST-MRI for HCC suRveillance in pAtients with high risK of liver cancer. BMJ Open 2024; 14:e083701. [PMID: 38367972 PMCID: PMC10875554 DOI: 10.1136/bmjopen-2023-083701] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Accepted: 01/23/2024] [Indexed: 02/19/2024] Open
Abstract
INTRODUCTION The surveillance of hepatocellular carcinoma (HCC) using semi-annual liver ultrasound (US) is justified in patients with cirrhosis. In this context, US has a low sensitivity (<30%) for the detection of HCC at the very early stage (ie, Barcelona clinic liver cancer (BCLC) 0, uninodular tumour <2 cm). The sensitivity of abbreviated liver MRI (AMRI) is reported to exceed 80%, but its use is hampered by costs and availability. Our hypothesis is that AMRI used as a screening examination in patients at high risk of HCC (>3% per year) could increase the rates of patients with a tumour detected at an early stage accessible to curative-intent treatment, and demonstrate its cost-effectiveness in this population. METHODS AND ANALYSIS The FASTRAK trial is a multicentre, randomised controlled trial with two parallel arms, aiming for superiority and conducted on patients at high risk for HCC (yearly HCC incidence >3%). Randomisation will be conducted on an individual basis with a centralised approach and stratification by centre. After inclusion in the trial, each patient will be randomly assigned to the experimental group (semi-annual US and AMRI) or the control group (semi-annual US alone). The main objective is to assess the cost/quality-adjusted life year and cost/patient detected with a BCLC 0 HCC in both arms. A total of 944 patients will be recruited in 37 tertiary French centres during a 36-month period and will be followed-up during 36 months. ETHICS AND DISSEMINATION The FASTRAK trial received ethical approval on 4 April 2022. Results will be disseminated via publication in peer-reviewed journals as well as presentation at international conferences. TRIAL REGISTRATION NUMBER Clinical trial number (ClinicaTrials.gov) NCT05095714.
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Affiliation(s)
| | | | | | - Pierre-André Natella
- Clinical Epidemiology and Ageing, Hôpitaux Universitaires Henri Mondor, Creteil, France
| | - Samia Baloul
- Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Isabelle Durand-Zaleski
- University of Paris, Paris, France
- URCEco, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Etienne Audureau
- CEPIA EA7376, Universite Paris-Est Creteil Val de Marne, Creteil, France
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Chen L, Wu T, Fan R, Qian YS, Liu JF, Bai J, Zheng B, Liu XL, Zheng D, Du LT, Jiang GQ, Wang YC, Fan XT, Deng GH, Wang CY, Shen F, Hu HP, Zhang QZ, Ye YN, Zhang J, Gao YH, Xia J, Yan HD, Liang MF, Yu YL, Sun FM, Gao YJ, Sun J, Zhong CX, Wang Y, Wang H, Kong F, Chen JM, Wen H, Wu BM, Wang CX, Wu L, Hou JL, Wang HY. Cell-free DNA testing for early hepatocellular carcinoma surveillance. EBioMedicine 2024; 100:104962. [PMID: 38184937 PMCID: PMC10808903 DOI: 10.1016/j.ebiom.2023.104962] [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: 09/11/2023] [Revised: 12/17/2023] [Accepted: 12/24/2023] [Indexed: 01/09/2024] Open
Abstract
BACKGROUND Liver cirrhosis (LC) is the highest risk factor for hepatocellular carcinoma (HCC) development worldwide. The efficacy of the guideline-recommended surveillance methods for patients with LC remains unpromising. METHODS A total of 4367 LCs not previously known to have HCC and 510 HCCs from 16 hospitals across 11 provinces of China were recruited in this multi-center, large-scale, cross-sectional study. Participants were divided into Stage Ⅰ cohort (510 HCCs and 2074 LCs) and Stage Ⅱ cohort (2293 LCs) according to their enrollment time and underwent Tri-phasic CT/enhanced MRI, US, AFP, and cell-free DNA (cfDNA). A screening model called PreCar Score was established based on five features of cfDNA using Stage Ⅰ cohort. Surveillance performance of PreCar Score alone or in combination with US/AFP was evaluated in Stage Ⅱ cohort. FINDINGS PreCar Score showed a significantly higher sensitivity for the detection of early/very early HCC (Barcelona stage A/0) in contrast to US (sensitivity of 51.32% [95% CI: 39.66%-62.84%] at 95.53% [95% CI: 94.62%-96.38%] specificity for PreCar Score; sensitivity of 23.68% [95% CI: 14.99%-35.07%] at 99.37% [95% CI: 98.91%-99.64%] specificity for US) (P < 0.01, Fisher's exact test). PreCar Score plus US further achieved a higher sensitivity of 60.53% at 95.08% specificity for early/very early HCC screening. INTERPRETATION Our study developed and validated a cfDNA-based screening tool (PreCar Score) for HCC in cohorts at high risk. The combination of PreCar Score and US can serve as a promising and practical strategy for routine HCC care. FUNDING A full list of funding bodies that contributed to this study can be found in Acknowledgments section.
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Affiliation(s)
- Lei Chen
- National Center of Liver Cancer, Navel Medical University, Shanghai, 210822, PR China; International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute/Hospital, Shanghai, 200438, PR China.
| | - Tong Wu
- National Center of Liver Cancer, Navel Medical University, Shanghai, 210822, PR China; Department of Radiation Oncology, General Hospital of Northern Theater Command, Shenyang, l10016, PR China
| | - Rong Fan
- Department of Infectious Diseases, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, PR China; Hepatology Unit, Shenzhen Hospital, Southern Medical University, Shenzhen, PR China
| | - Yun-Song Qian
- Hepatology Department, Ningbo Hwamei Hospital, University of Chinese Academy of Sciences, Ningbo, 315010, PR China
| | - Jing-Feng Liu
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, PR China
| | - Jian Bai
- Berry Oncology Corporation, Beijing, 100102, PR China
| | - Bo Zheng
- National Center of Liver Cancer, Navel Medical University, Shanghai, 210822, PR China; International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute/Hospital, Shanghai, 200438, PR China
| | - Xiao-Long Liu
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, PR China
| | - Dan Zheng
- Department of Gastroenterology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, PR China
| | - Lu-Tao Du
- Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, 247 Beiyuan Street, Jinan 250033, Shandong, PR China; Shandong Provincial Clinical Medicine Research Center for Clinical Laboratory, Jinan, 250033, PR China
| | - Guo-Qing Jiang
- Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou, 225001, PR China
| | - Ying-Chao Wang
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, PR China
| | - Xiao-Tang Fan
- Department of Hepatology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830000, PR China
| | - Guo-Hong Deng
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, PR China
| | - Chun-Ying Wang
- Xuzhou Infectious Diseases Hospital, Xuzhou, 221004, PR China
| | - Feng Shen
- Department of Hepatic Surgery IV, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, 200438, PR China
| | - He-Ping Hu
- Department of Hepatobiliary Medicine, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 210822, PR China
| | | | - Yi-Nong Ye
- The Department of Infectious Disease, The First People's Hospital of Foshan, Foshan City, 528000, PR China
| | - Jing Zhang
- Berry Oncology Corporation, Beijing, 100102, PR China
| | - Yan-Hang Gao
- The First Hospital of Jilin University, Jilin, 130021, PR China
| | - Jie Xia
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, PR China
| | - Hua-Dong Yan
- Hepatology Department, Ningbo Hwamei Hospital, University of Chinese Academy of Sciences, Ningbo, 315010, PR China
| | - Min-Feng Liang
- The Department of Infectious Disease, The First People's Hospital of Foshan, Foshan City, 528000, PR China
| | - Yan-Long Yu
- Chifeng Clinical Medical School of Inner Mongolia Medical University, Chifeng, 024000, PR China
| | - Fu-Ming Sun
- Berry Oncology Corporation, Beijing, 100102, PR China
| | - Yu-Jing Gao
- Xuzhou Infectious Diseases Hospital, Xuzhou, 221004, PR China
| | - Jian Sun
- Department of Infectious Diseases, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, PR China
| | - Chun-Xiu Zhong
- Department of Infectious Diseases, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, PR China
| | - Yin Wang
- Berry Oncology Corporation, Beijing, 100102, PR China
| | - Hui Wang
- Department of Hepatobiliary Medicine, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 210822, PR China
| | - Fei Kong
- The First Hospital of Jilin University, Jilin, 130021, PR China
| | - Jin-Ming Chen
- Chifeng Clinical Medical School of Inner Mongolia Medical University, Chifeng, 024000, PR China
| | - Hao Wen
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830000, PR China
| | - Bo-Ming Wu
- Hepatology Department, Ningbo Hwamei Hospital, University of Chinese Academy of Sciences, Ningbo, 315010, PR China
| | - Chuan-Xin Wang
- Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, 247 Beiyuan Street, Jinan 250033, Shandong, PR China; Shandong Provincial Clinical Medicine Research Center for Clinical Laboratory, Jinan, 250033, PR China.
| | - Lin Wu
- Berry Oncology Corporation, Beijing, 100102, PR China.
| | - Jin-Lin Hou
- Department of Infectious Diseases, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, PR China; Hepatology Unit, Shenzhen Hospital, Southern Medical University, Shenzhen, PR China.
| | - Hong-Yang Wang
- National Center of Liver Cancer, Navel Medical University, Shanghai, 210822, PR China; International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute/Hospital, Shanghai, 200438, PR China; Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer (SMMU), Ministry of Education, Shanghai, 200438, PR China; Shanghai Key Laboratory of Hepatobiliary Tumor Biology (EHBH), Shanghai, 200438, PR China.
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Li S, Kong D, Zhang W, Li Y, Wang H, Yang R, Sun Q, Wang Z, Zhang Z. Low SAA4 gene expression is associated with advanced HCC stage and a poor prognosis. Clin Exp Med 2024; 24:31. [PMID: 38300370 PMCID: PMC10834558 DOI: 10.1007/s10238-023-01279-8] [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: 05/30/2023] [Accepted: 11/20/2023] [Indexed: 02/02/2024]
Abstract
At present, although there are tumor markers for hepatocellular carcinoma (HCC), markers with better predictive efficiency are needed. SAA4 gene expression in liver tumor and paracancerous tissues was analyzed using The Cancer Genome Atlas database. The differentially expressed genes (DEGs) were analyzed and visualized by heatmap and volcano plot. Survival analysis was performed based on SAA4 expression. SAA4 expression was compared in patients grouped based on clinicopathological features, and gene set enrichment analysis (GSEA) was conducted. Immunohistochemical staining was used to verify the SAA4 protein staining intensity from The Human Protein Atlas database and our center's samples. The diagnostic value of SAA4 for HCC was evaluated by receiver operating characteristic curves. SAA4 was expressed at low levels in HCC tissues, and low SAA4 expression was associated with a poor prognosis in HCC. In addition, SAA4 expression decreased with HCC progression. There were 188 upregulated DEGs and 1551 downregulated DEGs between the high and low SAA4 expression groups. Complement and coagulation cascades, fatty acid metabolism, and ECM receptor interaction were significantly enriched in the GSEA. SAA4 had good predictive efficacy for HCC and even early HCC and was superior to AFP. In general, low SAA4 expression was associated with advanced HCC stage and a poor prognosis. In addition, SAA4 may be helpful for the diagnosis of early HCC and may become a novel tumor marker with good predictive power for HCC.
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Affiliation(s)
- Shilong Li
- Department of Gastrointestinal Surgery, Shaoxing Second Hospital, Zhejiang, China
| | - Dejun Kong
- Biological Sample Resource Sharing Center, Tianjin First Central Hospital, Tianjin, China
- School of Medicine, Nankai University, Tianjin, China
| | - Weiqi Zhang
- School of Medicine, Nankai University, Tianjin, China
| | - Yan Li
- Biological Sample Resource Sharing Center, Tianjin First Central Hospital, Tianjin, China
| | - Hao Wang
- The First Central Clinical School, Tianjin Medical University, Tianjin, China
| | - Ruining Yang
- The First Central Clinical School, Tianjin Medical University, Tianjin, China
| | - Qian Sun
- The First Central Clinical School, Tianjin Medical University, Tianjin, China
| | - Zhenglu Wang
- Biological Sample Resource Sharing Center, Tianjin First Central Hospital, Tianjin, China.
| | - Zhongwei Zhang
- Department of Gastrointestinal Surgery, Shaoxing Second Hospital, Zhejiang, China.
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Suhail Najm Alareer H, Arian A, Fotouhi M, Taher HJ, Dinar Abdullah A. Evidence Supporting Diagnostic Value of Liver Imaging Reporting and Data System for CT- and MR Imaging-based Diagnosis of Hepatocellular Carcinoma: A Systematic Review and Meta-analysis. J Biomed Phys Eng 2024; 14:5-20. [PMID: 38357604 PMCID: PMC10862115 DOI: 10.31661/jbpe.v0i0.2211-1562] [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: 11/08/2022] [Accepted: 03/12/2023] [Indexed: 02/16/2024]
Abstract
Background Based on the Liver Imaging Data and Reporting System (LI-RADS) guidelines, Hepatocellular Carcinoma (HCC) can be diagnosed using imaging criteria in patients at risk of HCC. Objective This study aimed to assess the diagnostic value of LI-RADS in high-risk patients with HCC. Material and Methods This systematic review is conducted on international databases, including Google Scholar, Web of Science, PubMed, Embase, PROQUEST, and Cochrane Library, with appropriate keywords. Using the binomial distribution formula, the variance of each study was calculated, and all the data were analyzed using STATA version 16. The pooled sensitivity and specificity were determined using a random-effects meta-analysis approach. Also, we used the chi-squared test and I2 index to calculate heterogeneity among studies, and Funnel plots and Egger tests were used for evaluating publication bias. Results The pooled sensitivity was estimated at 0.80 (95% CI 0.76-0.84). According to different types of Liver Imaging Reporting and Data Systems (LI-RADS), the highest pooled sensitivity was in version 2018 (0.83 (95% CI 0.79-0.87) (I2: 80.6%, P of chi 2 test for heterogeneity <0.001 and T2: 0.001). The pooled specificity was estimated as 0.89 (95% CI 0.87-0.92). According to different types of LI-RADS, the highest pooled specificity was in version 2014 (93.0 (95% CI 89.0-96.0) (I2: 81.7%, P of chi 2 test for heterogeneity <0.001 and T2: 0.001). Conclusion LI-RADS can assist radiologists in achieving the required sensitivity and specificity in high-risk patients suspected to have HCC. Therefore, this strategy can serve as an appropriate tool for identifying HCC.
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Affiliation(s)
- Hayder Suhail Najm Alareer
- Department of Radiology, College of Health and Medical Technology, Al-Ayen University, Thi-Qar, 64001, Iraq
| | - Arvin Arian
- Cancer Institute ADIR, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | - Maryam Fotouhi
- Quantitative MR Imaging and Spectroscopy Group (QMISG), Research Centre for Molecular and Cellular Imaging (RCMCI), Advanced Medical Technologies and Equipment Institute (AMTEI), Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | | | - Ayoob Dinar Abdullah
- Department of Radiology Technology, Al-Manara College for Medical Sciences, Missan, Iraq
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Heo S, Choi WM. Non-Contrast Abbreviated Magnetic Resonance Imaging: A Cost-Effective Rookie in Hepatocellular Carcinoma Surveillance for Cirrhotic Patients. Gut Liver 2024; 18:7-9. [PMID: 38221817 PMCID: PMC10791505 DOI: 10.5009/gnl230537] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/16/2024] Open
Affiliation(s)
- Subin Heo
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Won-Mook Choi
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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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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Ringe KI, Wang J, Deng Y, Pi S, Geahchan A, Taouli B, Bashir MR. Abbreviated MRI Protocols in the Abdomen and Pelvis. J Magn Reson Imaging 2024; 59:58-69. [PMID: 37144673 DOI: 10.1002/jmri.28764] [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: 01/26/2023] [Revised: 04/13/2023] [Accepted: 04/13/2023] [Indexed: 05/06/2023] Open
Abstract
Abbreviated MRI (AMRI) protocols rely on the acquisition of a limited number of sequences tailored to a specific question. The main objective of AMRI protocols is to reduce exam duration and costs, while maintaining an acceptable diagnostic performance. AMRI is of increasing interest in the radiology community; however, challenges limiting clinical adoption remain. In this review, we will address main abdominal and pelvic applications of AMRI in the liver, pancreas, kidney, and prostate, including diagnostic performance, pitfalls, limitations, and cost effectiveness will also be discussed. Level of Evidence: 3 Technical Efficacy Stage: 3.
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Affiliation(s)
- Kristina I Ringe
- Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany
| | - Jin Wang
- Department of Radiology, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Ying Deng
- Department of Radiology, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Shan Pi
- Department of Radiology, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Amine Geahchan
- Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Bachir Taouli
- Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Mustafa R Bashir
- Department of Radiology, Center for Advanced Magnetic Resonance Development, Duke University Medical Center, Durham, North Carolina, USA
- Division of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA
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48
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Souaid CK, Marty O, Medlij C. A rare and challenging case of extrahepatic costal metastases from an unknown primary hepatocellular carcinoma. GASTROENTEROLOGY AND HEPATOLOGY FROM BED TO BENCH 2024; 17:93-99. [PMID: 38737936 PMCID: PMC11080690 DOI: 10.22037/ghfbb.v17i1.2812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Accepted: 11/11/2023] [Indexed: 05/14/2024]
Abstract
Hepatocellular carcinoma (HCC) typically presents with a primary hepatic mass. Nevertheless, on rare occasions, the initial presentation can be exclusively related to extrahepatic metastases and the most common sites of metastases are the lungs, lymph nodes, bones, and adrenal glands. While, bone metastases are generally accompanied by multiple metastatic spreads elsewhere in the body or previously diagnosed HCC, cases of solitary bone metastases with no liver lesion at imaging have been reported. Indeed, two rare entities of HCC have been reported in the literature which are the ectopic hepatocellular carcinoma and the infiltrative type of hepatocellular carcinoma with a very challenging radiologic diagnosis and poor prognosis. In this article, we present a case of extrahepatic costal metastases of hepatocellular carcinoma, which was diagnosed through a bone biopsy, with no focal lesion on liver imaging including ultrasound, multiphase MRI, and CT scan except for the presence of a portal vein thrombosis. It is important to consider the possibility of HCC metastases when evaluating rapidly growing extrahepatic lesions in patients with chronic liver disease and to consider the tumor characteristics and imaging findings as well as limitations to make accurate and timely diagnosis leading to improved patient management. Our patient had probably an infiltrating HCC because of two prominent factors: the presence of portal vein thrombosis and a markedly elevated alpha-fetoprotein (AFP). A liver biopsy was crucial in order to confirm the diagnosis but unfortunately it could not be performed because of the unexpected death of the patient due to hemorrhagic shock. It is also worth noting in this case, that the elevated level of AFP raised the suspicion on an underlying HCC and contributed to more elaborate diagnostic tests.
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Affiliation(s)
- Christophe-Karl Souaid
- Department of gastroenterology, Paris Saint Joseph Hospital Group, Paris, France
- Holy spirit university of Kaslik, Jounieh, Lebanon
| | - Olivier Marty
- Department of gastroenterology, Paris Saint Joseph Hospital Group, Paris, France
| | - Cynthia Medlij
- Department of gastroenterology, Paris Saint Joseph Hospital Group, Paris, France
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49
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Koh JH, Wang M, Suzuki H, Muthiah M, Ng CH, Huang DQ. NAFLD and NAFLD-related HCC in Asia: Burden and Surveillance. J Clin Exp Hepatol 2024; 14:101213. [PMID: 38076360 PMCID: PMC10701133 DOI: 10.1016/j.jceh.2023.06.013] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Accepted: 06/30/2023] [Indexed: 06/21/2024] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is rapidly emerging as a leading etiology of chronic liver disease (CLD) in Asia. The increasing incidence of NAFLD is projected to drive a surge in NAFLD-related hepatocellular carcinoma (HCC). A notable characteristic of NAFLD-HCC is its capacity for development in individuals without cirrhosis in more than a third of patients. Most practice guidelines recommend biannual ultrasound screening for patients with cirrhosis. In cases of severe limitations to ultrasound visualisation, cross-sectional abdominal imaging may be warranted. Improved strategies for HCC risk stratification are required for people with NAFLD but without cirrhosis. In this Review, we discuss the evolving trends of NAFLD and HCC in Asia, and implications for surveillance.
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Affiliation(s)
- Jia H. Koh
- Department of Medicine, National University Hospital, Singapore, Singapore
| | - Meng Wang
- Department of Medicine, National University Hospital, Singapore, Singapore
| | - Hiroyuki Suzuki
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Mark Muthiah
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Cheng H. Ng
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Daniel Q. Huang
- NAFLD Research Center, University of California at San Diego, USA
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50
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Zhang Z, Wu H, Zhang Y, Shen C, Zhou F. Dietary antioxidant quercetin overcomes the acquired resistance of Sorafenib in Sorafenib-resistant hepatocellular carcinoma cells through epidermal growth factor receptor signaling inactivation. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:559-574. [PMID: 37490119 DOI: 10.1007/s00210-023-02605-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Accepted: 06/25/2023] [Indexed: 07/26/2023]
Abstract
Sorafenib (SOR) is a molecular targeting agent commonly utilized as a primary treatment for advanced and inoperable hepatocellular carcinoma (HCC). Regrettably, the effectiveness of SOR is frequently hindered by the resistance of multiple HCC cases. The current investigation endeavors to examine the potential of the natural product quercetin (QUE) in reversing the acquired resistance of SOR-resistant cells, known as Huh7R, to SOR. Moreover, this study aims to elucidate the underlying molecular mechanism that contributes to this phenomenon. The results demonstrated that QUE significantly impeded proliferation and stimulated apoptosis in Huh7R cells, while also suppressing the growth of transplanted tumors. The impact of QUE enhanced the efficacy of SOR treatment for Huh7R. Additionally, bioinformatic and western blot analyses indicated that the underlying mechanisms may be associated with EGFR tyrosine kinase inhibitor resistance, the PI3K-AKT signaling pathway, and HCC. Furthermore, molecular docking and dynamics simulation assays revealed that QUE exhibited strong affinity and stability towards its hub targets, EGFR and AKT1. It is noteworthy that the activation of EGFR by its ligand, EGF, mitigated the effects of co-treatment with QUE and SOR. These findings suggest that QUE might potentially serve as a therapeutic agent in treating as well as facilitating SOR against Huh7R cells, which has substantial clinical and research implications for the treatment of acquired resistance to SOR in HCC.
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Affiliation(s)
- Zhengguang Zhang
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Jiangsu, Nanjing, China.
| | - Haitao Wu
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Jiangsu, Nanjing, China
| | - Yajie Zhang
- Central Laboratory, Nanjing Hospital of Chinese Medicine, Affiliated to Nanjing University of Chinese Medicine, Jiangsu, Nanjing, China
| | - Cunsi Shen
- Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu, Nanjing, China.
| | - Fuqiong Zhou
- Central Laboratory, Nanjing Hospital of Chinese Medicine, Affiliated to Nanjing University of Chinese Medicine, Jiangsu, Nanjing, China.
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