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Mohnasky M, Gad S, Moon A, Barritt AS, Charalel RA, Eckblad C, Caddell A, Xing M, Kokabi N. Hepatocellular Carcinoma Screening: From Current Standard of Care to Future Directions. J Am Coll Radiol 2025; 22:260-268. [PMID: 40044304 DOI: 10.1016/j.jacr.2024.10.014] [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: 09/04/2024] [Revised: 10/09/2024] [Accepted: 10/23/2024] [Indexed: 05/13/2025]
Abstract
Hepatocellular carcinoma (HCC) represents a significant portion of global cancer incidence and mortality. Screening with ultrasound with or without alpha-fetoprotein is recommended for those at high-risk. Although screening can lead to earlier treatment and better outcomes, existing screening paradigms have several flaws. Ultrasound does not capture all early lesions and has lower efficacy in specific populations such as patients with obesity or those with metabolic dysfunction-associated steatotic liver disease (MASLD). Additionally, individuals with noncirrhotic MASLD and chronic hepatitis C also develop HCC, although not at high enough rates to justify screening based on current standards. These individuals, however, represent a substantial proportion of new HCC cases given rising MASLD rates and the endemic nature of hepatitis C in certain regions. Risk-stratifying these populations may reveal subsets that are higher risk and warrant screening. Several imaging advances, including contrast-enhanced ultrasound and abbreviated MRI protocols, may improve detection compared with the current approach. Evaluation of risk stratification and validation of these new imaging methods via clinical trials would likely lead to adjusting screening guidelines. This narrative review provides a diagnostic and interventional radiology-focused summary of the HCC screening guidelines and their recent evolution and highlights emerging imaging methods as potential screening tools of the future.
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Affiliation(s)
- Michael Mohnasky
- University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, North Carolina.
| | - Sandra Gad
- University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, North Carolina; Saint George's University, School of Medicine, West Indies, Grenada
| | - Andrew Moon
- Assistant Professor of Medicine, Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, North Carolina
| | - A Sidney Barritt
- Professor of Medicine, Director of Hepatology, Transplant Hepatology Program Director, Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, North Carolina
| | - Resmi A Charalel
- Assistant Professor of Population Health Science, Assistant Professor of Radiology, Division of Interventional Radiology, Department of Radiology, Weill Cornell Medicine, New York, New York
| | - Caroline Eckblad
- University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, North Carolina
| | - Andrew Caddell
- University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, North Carolina
| | - Minzhi Xing
- Assistant Professor of Public Health Leadership and Practice, Gillings School of Global Public Health; Adjunct Assistant Professor of Radiology, University of North Carolina School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Nima Kokabi
- Associate Professor of Radiology, Vice Chair of Clinical Research, Director of Interventional Oncology, and Director of Cancer Imaging, Department of Radiology, University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, North Carolina
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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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Singal AG, Daher D, Narasimman M, Yekkaluri S, Liu Y, Cerda V, Banala C, Khan A, Lee M, Seif El Dahan K, Murphy CC, Kramer JR, Hernaez R. Benefits and harms of hepatocellular carcinoma screening outreach in patients with cirrhosis: a multicenter randomized clinical trial. J Natl Cancer Inst 2025; 117:262-269. [PMID: 39288308 PMCID: PMC11807434 DOI: 10.1093/jnci/djae228] [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: 07/09/2024] [Revised: 08/06/2024] [Accepted: 08/29/2024] [Indexed: 09/19/2024] Open
Abstract
BACKGROUND The value of hepatocellular carcinoma screening is defined by the balance of benefits from early tumor detection vs harms because of false-positive results. We evaluated the value of a mailed outreach strategy for hepatocellular carcinoma screening in patients with cirrhosis. METHODS We conducted a multicenter pragmatic randomized clinical trial comparing mailed outreach for hepatocellular carcinoma screening (n = 1436) and usual care with visit-based screening (n = 1436) among patients with cirrhosis at 3 health systems from March 2018 to September 2021. Outcomes of interest were early stage hepatocellular carcinoma detection (ie, screening benefit) and diagnostic evaluation for false-positive or indeterminate results (ie, screening harm). Screening harm was categorized as mild, moderate, and severe based on number and type of diagnostic exams. All patients were included in intention-to-screen analyses. RESULTS Of 125 patients diagnosed with hepatocellular carcinoma (67 outreach and 58 usual care), 71.2% were found at an early stage per the Milan criteria. Early tumor detection did not statistically significantly differ between the outreach and usual care arms (64.2% vs 79.3%; P = .06). The proportion of patients with physical harms also did not differ between the outreach and usual care arms (10.8% vs 10.7%; P = .95) with 5.9% in both arms having mild harms; 4.0% and 3.8%, respectively, with moderate harms; and 0.9% and 1.0%, respectively, with severe harms. CONCLUSION Most patients enrolled in hepatocellular carcinoma screening were detected at an early stage, and a minority experienced physical harms. A mailed outreach strategy did not increase early hepatocellular carcinoma detection or physical harms compared with usual care. CLINICAL TRIALS NUMBER NCT02582918 and NCT03756051.
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Affiliation(s)
- Amit G Singal
- Department of Internal Medicine, University of Texas Southwestern Medical Center and Parkland Health Hospital System, Dallas, TX, USA
| | - Darine Daher
- Department of Internal Medicine, University of Texas Southwestern Medical Center and Parkland Health Hospital System, Dallas, TX, USA
| | - Manasa Narasimman
- Department of Internal Medicine, University of Texas Southwestern Medical Center and Parkland Health Hospital System, Dallas, TX, USA
| | - Sruthi Yekkaluri
- Department of Internal Medicine, University of Texas Southwestern Medical Center and Parkland Health Hospital System, Dallas, TX, USA
| | - Yan Liu
- Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA
| | - Vanessa Cerda
- O’Donnell School of Public Health, University of Texas Southwestern Medical Center and Parkland Health Hospital System, Dallas, TX, USA
| | - Chaitra Banala
- Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX, USA
| | - Aisha Khan
- Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA
| | - MinJae Lee
- O’Donnell School of Public Health, University of Texas Southwestern Medical Center and Parkland Health Hospital System, Dallas, TX, USA
| | - Karim Seif El Dahan
- Department of Internal Medicine, University of Texas Southwestern Medical Center and Parkland Health Hospital System, Dallas, TX, USA
| | - Caitlin C Murphy
- Department of Internal Medicine, University of Texas Southwestern Medical Center and Parkland Health Hospital System, Dallas, TX, USA
| | - Jennifer R Kramer
- Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA
- Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX, USA
| | - Ruben Hernaez
- Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA
- Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX, USA
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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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El-Azab GI, El-Helw GAA, Elsabaawy MMA, Kohla MAS, Omar YAM. Evaluation of screening program for hepatocellular carcinoma at a single center. EGYPTIAN LIVER JOURNAL 2025; 15:2. [DOI: 10.1186/s43066-025-00404-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Accepted: 01/16/2025] [Indexed: 03/04/2025] Open
Abstract
Abstract
Background
Hepatocellular carcinoma (HCC) is the seventh most common cancer in the world and is a form of liver cancer that starts in the cells of the liver. The best way to increase the chances of survival for people at high risk for HCC is to detect it early through regular monitoring. For monitoring purposes, it is recommended to conduct ultrasound exams every 4 to 6 months, sometimes in combination with alpha-fetoprotein tests.
Aim of the work
Assess the HCC surveillance and its ability to detect HCC patients early on and improve their management.
Patients and methods
The study involved 300 patients of hepatocellular carcinoma (HCC) investigated at Menoufia University’s Institute of National Liver in Egypt. Patients were evaluated using the Liver Cancer of Barcelona Clinic (BCLC) staging system. Furthermore, the patients were classified into three surveillance categories: no surveillance, routine surveillance, and sporadic surveillance.
Results
A substantial difference statistically among the groups that received and did not receive surveillance with consideration for the stage of hepatocellular carcinoma (HCC) in particular was found. Patients who were observed usually got their diagnoses earlier. Those who were not under surveillance frequently had advanced cases of hepatocellular carcinoma upon diagnosis (HCC).
Conclusion
High-risk patients were regularly investigated for having HCC is necessary for early disease detection, appropriate therapy, and improved survival. Consistent monitoring with AFP and ultrasound allows for early detection of HCC.
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Kanneganti M, Al-Hasan M, Bourque S, Deodhar S, Yang JD, Huang DQ, Kulkarni AV, Gopal P, Parikh ND, Kanwal F, Patel MS, Singal AG. Older Age But Not Comorbidity is Associated with Worse Survival in Patients with Hepatocellular Carcinoma. Clin Gastroenterol Hepatol 2024:S1542-3565(24)01038-3. [PMID: 39571877 DOI: 10.1016/j.cgh.2024.10.015] [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: 07/05/2024] [Revised: 09/28/2024] [Accepted: 10/05/2024] [Indexed: 12/13/2024]
Abstract
BACKGROUND & AIMS Age and comorbidity are key factors in assessing patient prognosis and informing stopping rules for cancer screening eligibility, but their impact has not been rigorously evaluated in patients with hepatocellular carcinoma (HCC). METHODS We conducted a retrospective cohort study of patients diagnosed with HCC at 2 health systems between January 2010 and February 2023. We used multivariable logistic regression and Cox proportional hazards models to evaluate the associations between older age (≥65 years) and comorbidity burden (Charlson Comorbidity Index) with early-stage presentation, curative treatment receipt, and overall survival. We performed subgroup analyses in patients with early-stage HCC. RESULTS We identified 2002 patients with HCC (median age, 61 years; 76% male; 21% early-stage), with a median survival of 15.7 months. In adjusted analyses, curative treatment receipt was associated with higher comorbidity but not older age. Conversely, overall survival was significantly associated with older age (hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.06-1.47) but not high comorbidity (HR, 0.92; 95% CI, 0.77-1.09). Older age continued to be associated with worse survival among patients with early-stage HCC (HR, 1.99; 95% CI, 1.45-2.73) and those who underwent curative treatment (HR, 1.52; 95% CI, 1.10-2.10). Median survival for younger versus older individuals was 20 versus 14 months overall, 65 versus 49 months for patients with early-stage HCC, and 113 versus 60 months for those with curative treatment. CONCLUSIONS Older age but not comorbidity burden is associated with worse survival, including among patients with early-stage HCC. Further studies are needed to define the role of comorbidity in HCC prognostication.
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Affiliation(s)
- Mounika Kanneganti
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas
| | - Mohammed Al-Hasan
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas
| | - Samantha Bourque
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas
| | - Sneha Deodhar
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas
| | - Ju Dong Yang
- Karsh Division of Gastroenterology and Hepatology, Cedars Sinai Medical Center, Los Angeles, California
| | - Daniel Q Huang
- Department of Internal Medicine, National University Health System, Singapore, Singapore
| | - Anand V Kulkarni
- Department of Hepatology and Liver Transplantation, AIG Hospitals, Hyderabad, India
| | - Purva Gopal
- Department of Pathology, UT Southwestern Medical Center, Dallas, Texas
| | - Neehar D Parikh
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
| | - Fasiha Kanwal
- Department of Internal Medicine, Baylor College of Medicine, Houston, Texas
| | - Madhukar S Patel
- Department of Surgery, UT Southwestern Medical Center, Dallas, Texas
| | - Amit G Singal
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas.
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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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Suddle A, Reeves H, Hubner R, Marshall A, Rowe I, Tiniakos D, Hubscher S, Callaway M, Sharma D, See TC, Hawkins M, Ford-Dunn S, Selemani S, Meyer T. British Society of Gastroenterology guidelines for the management of hepatocellular carcinoma in adults. Gut 2024; 73:1235-1268. [PMID: 38627031 PMCID: PMC11287576 DOI: 10.1136/gutjnl-2023-331695] [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: 12/06/2023] [Accepted: 03/19/2024] [Indexed: 05/01/2024]
Abstract
Deaths from the majority of cancers are falling globally, but the incidence and mortality from hepatocellular carcinoma (HCC) is increasing in the United Kingdom and in other Western countries. HCC is a highly fatal cancer, often diagnosed late, with an incidence to mortality ratio that approaches 1. Despite there being a number of treatment options, including those associated with good medium to long-term survival, 5-year survival from HCC in the UK remains below 20%. Sex, ethnicity and deprivation are important demographics for the incidence of, and/or survival from, HCC. These clinical practice guidelines will provide evidence-based advice for the assessment and management of patients with HCC. The clinical and scientific data underpinning the recommendations we make are summarised in detail. Much of the content will have broad relevance, but the treatment algorithms are based on therapies that are available in the UK and have regulatory approval for use in the National Health Service.
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Affiliation(s)
- Abid Suddle
- King's College Hospital NHS Foundation Trust, London, UK
| | - Helen Reeves
- Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK
| | - Richard Hubner
- Department of Oncology, The Christie NHS Foundation Trust, Manchester, UK
| | | | - Ian Rowe
- University of Leeds, Leeds, UK
- St James's University Hospital, Leeds, UK
| | - Dina Tiniakos
- Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
| | - Stefan Hubscher
- Department of Pathology, University of Birmingham, Birmingham, UK
| | - Mark Callaway
- Division of Diagnostics and Therapies, University Hospitals Bristol NHS Trust, Bristol, UK
| | | | - Teik Choon See
- Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Maria Hawkins
- Department of Medical Physics and Biomedical Engineering, University College London, London, UK
| | | | - Sarah Selemani
- King's College Hospital NHS Foundation Trust, London, UK
| | - Tim Meyer
- Department of Oncology, University College, London, UK
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Daher D, Dahan KSE, Yekkaluri S, Gopal P, Rich NE, Parikh ND, Murphy CC, Singal AG. Proportion of Time Covered by Hepatocellular Carcinoma Surveillance in Patients With Cirrhosis. Am J Gastroenterol 2024; 119:875-882. [PMID: 37975606 PMCID: PMC11068493 DOI: 10.14309/ajg.0000000000002596] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Accepted: 10/09/2023] [Indexed: 11/19/2023]
Abstract
INTRODUCTION Hepatocellular carcinoma (HCC) surveillance is associated with improved early tumor detection, but effectiveness is limited by underuse. We characterized adherence to HCC surveillance using proportion of time covered (PTC) and estimated its association with clinical outcomes among patients with cirrhosis. METHODS We conducted a retrospective cohort study of patients diagnosed with HCC between January 2008 and December 2022 at 2 large US health systems. We characterized PTC by imaging in the 12 and 24 months before HCC diagnosis. We used multivariable logistic and Cox regression analyses to assess the association between PTC and early HCC detection, receipt of curative treatment, and overall survival. RESULTS Among 2,027 patients with HCC, 331 (51.4% Barcelona Clinic Liver Cancer 0/A) had been followed up for at least 12 months before diagnosis. The median PTC was 24.9% (interquartile range 1.1%-50.7%), with only 16.0% having semiannual imaging and 42.0% having annual surveillance. Semiannual and annual surveillance decreased to 6.3% and 29.6% when assessed over 24 months, although the median PTC remained unchanged at 24.9%. Receipt of gastroenterology/hepatology care had the strongest association with PTC, with median PTC of 36.7% and 3.8% for those with and without gastroenterology/hepatology care, respectively. PTC was independently associated with improved early HCC detection, curative treatment receipt, and overall survival. The median survival was 15.7, 26.8, and 32.7 months among those with PTC of <25% (n = 168 patients), PTC 25%-50% (n = 69 patients), and PTC >50% (n = 94 patients), respectively. DISCUSSION The proportion of time covered by HCC surveillance in patients with cirrhosis remains low, highlighting a need for multilevel interventions.
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Affiliation(s)
- Darine Daher
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA
| | - Karim Seif El Dahan
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA
| | - Sruthi Yekkaluri
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA
| | - Purva Gopal
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA
| | - Nicole E. Rich
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA
| | - Neehar D. Parikh
- Department of Internal Medicine, University of Michigan, Ann Arbor MI
| | | | - Amit G. Singal
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA
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Daher D, Seif El Dahan K, Rich NE, Tayob N, Merrill V, Huang DQ, Yang JD, Kulkarni AV, Kanwal F, Marrero J, Parikh N, Singal AG. Hepatocellular Carcinoma Screening in a Contemporary Cohort of At-Risk Patients. JAMA Netw Open 2024; 7:e248755. [PMID: 38683607 PMCID: PMC11059036 DOI: 10.1001/jamanetworkopen.2024.8755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Accepted: 02/26/2024] [Indexed: 05/01/2024] Open
Abstract
Importance Cohort studies demonstrating an association of hepatocellular carcinoma (HCC) screening with reduced mortality are prone to lead-time and length-time biases. Objective To characterize the clinical benefits of HCC screening, adjusting for lead-time and length-time biases, in a diverse, contemporary cohort of at-risk patients. Design, Setting, and Participants This retrospective cohort study of patients with HCC was conducted between January 2008 and December 2022 at 2 large US health systems. Data analysis was performed from September to November 2023. Main Outcomes and Measures The primary outcome was screen-detected HCC, defined by abnormal screening-intent abdominal imaging or α-fetoprotein level within 6 months before diagnosis. Cox regression analysis was used to characterize differences in overall survival between patients with screen-detected and non-screen-detected HCC; lead-time and length-time adjustments were calculated using the Duffy parametric formula. Results Among 1313 patients with HCC (mean [SD] age, 61.7 [9.6] years; 993 male [75.6%]; 739 [56.3%] with Barcelona Clinic Liver Cancer stage 0/A disease), HCC was screen-detected in 556 (42.3%) and non-screen detected in 757 (57.7%). Patients with screen-detected HCC had higher proportions of early-stage HCC (393 patients [70.7%] vs 346 patients [45.7%]; risk ratio [RR], 1.54; 95% CI, 1.41-1.70) and curative treatment receipt (283 patients [51.1%] vs 252 patients [33.5%]; RR, 1.52; 95% CI, 1.34-1.74) compared with patients with non-screen-detected HCC. The screen-detected group had significantly lower mortality, which persisted after correcting for lead-time bias (hazard ratio, 0.75; 95% CI, 0.65-0.87) in fully adjusted models. Both groups had similar tumor doubling times (median [IQR], 3.8 [2.2-10.7] vs 5.6 [1.7-11.4] months) and proportions of indolent tumors (28 patients [35.4%] vs 24 patients [38.1%]; RR, 0.93; 95% CI, 0.60-1.43). Adjustment for length-time bias decreased survival estimates, although 3-year and 5-year survival for patients with screen-detected HCC remained longer than that for patients with non-screen-detected HCC. Conclusions and Relevance The findings of this cohort study suggest that HCC screening is associated with reduced mortality even after accounting for lead-time and length-time biases. However, these biases should be considered in future studies.
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Affiliation(s)
- Darine Daher
- Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas
| | - Karim Seif El Dahan
- Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas
| | - Nicole E. Rich
- Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas
| | - Nabihah Tayob
- Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts
| | - Vincent Merrill
- Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas
| | - Daniel Q. Huang
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Ju Dong Yang
- Department of Internal Medicine, Cedars Sinai Medical Center, Los Angeles, California
| | - Anand V. Kulkarni
- Department of Hepatology and Liver Transplantation, AIG Hospitals, Hyderabad India
| | - Fasiha Kanwal
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas
- Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
| | - Jorge Marrero
- Department of Internal Medicine, University of Pennsylvania, Philadelphia
| | - Neehar Parikh
- Department of Internal Medicine, University of Michigan, Ann Arbor
| | - Amit G. Singal
- Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas
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Rogal SS, Taddei TH, Monto A, Yakovchenko V, Patton H, Merante M, Spoutz P, Chia L, Yudkevich J, Aytaman A, Rabiee A, John BV, Blechacz B, Cai CX, Gilles H, Shah AS, McCurdy H, Puri P, Jou J, Mazhar K, Dominitz JA, Anwar J, Morgan TR, Ioannou GN. Hepatocellular Carcinoma Diagnosis and Management in 2021: A National Veterans Affairs Quality Improvement Project. Clin Gastroenterol Hepatol 2024; 22:324-338. [PMID: 37460005 PMCID: PMC10788380 DOI: 10.1016/j.cgh.2023.07.002] [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: 04/12/2023] [Revised: 06/16/2023] [Accepted: 07/02/2023] [Indexed: 08/13/2023]
Abstract
BACKGROUND & AIMS The coronavirus disease-2019 pandemic profoundly disrupted preventative health care services including cancer screening. As the largest provider of cirrhosis care in the United States, the Department of Veterans Affairs (VA) National Gastroenterology and Hepatology Program aimed to assess factors associated with hepatocellular carcinoma (HCC) stage at diagnosis, treatment, and survival. METHODS Veterans with a new diagnosis of HCC in 2021 were identified from electronic health records (N = 2306). Structured medical record extraction was performed by expert reviewers in a 10% random subsample of Veterans with new HCC diagnoses. Factors associated with stage at diagnosis, receipt of treatment, and survival were assessed using multivariable models. RESULTS Among 199 patients with confirmed HCC, the average age was 71 years and most (72%) had underlying cirrhosis. More than half (54%) were at an early stage (T1 or T2) at diagnosis. Less-advanced liver disease, number of imaging tests adequate for HCC screening, HCC diagnosis in the VA, and receipt of VA primary care were associated significantly with early stage diagnosis. HCC-directed treatments were administered to 145 (73%) patients after a median of 37 days (interquartile range, 19-54 d) from diagnosis, including 70 (35%) patients who received potentially curative treatments. Factors associated with potentially curative (vs no) treatments included HCC screening, early stage at diagnosis, and better performance status. Having fewer comorbidities and better performance status were associated significantly with noncurative (vs no) treatment. Early stage diagnosis, diagnosis in the VA system, and receipt of curative treatment were associated significantly with survival. CONCLUSIONS These results highlight the importance of HCC screening and engagement in care for HCC diagnosis, treatment, and survival while demonstrating the feasibility of developing a national quality improvement agenda for HCC screening, diagnosis, and treatment.
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Affiliation(s)
- Shari S Rogal
- VA Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania; Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.
| | - Tamar H Taddei
- VA Connecticut Healthcare System, West Haven, Connecticut; Section of Digestive Diseases, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
| | - Alexander Monto
- San Francisco VA Health Care System, San Francisco, California
| | - Vera Yakovchenko
- VA Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania
| | - Heather Patton
- Gastroenterology Section, Jennifer Moreno VA San Diego Healthcare System, San Diego, California
| | - Monica Merante
- VA Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania
| | - Patrick Spoutz
- Pharmacy Benefits Management, Veterans Integrated Service Network 20, Vancouver, Washington
| | - Linda Chia
- Pharmacy Benefits Management, Veterans Integrated Service Network 20, Vancouver, Washington
| | - Jennifer Yudkevich
- VA New York Harbor Healthcare System, Brooklyn Campus, Brooklyn, New York
| | - Ayse Aytaman
- VA New York Harbor Healthcare System, Brooklyn Campus, Brooklyn, New York; SUNY Health Science Center Brooklyn, Brooklyn, New York
| | - Atoosa Rabiee
- Washington DC VA Medical Center, Washington, District of Columbia
| | - Binu V John
- Division of Gastroenterology and Hepatology, Miami VA Healthcare System, Miami, Florida; Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida
| | - Boris Blechacz
- Department of Gastroenterology and Hepatology, VA South Texas Health Care System, San Antonio, Texas
| | - Cindy X Cai
- Department of Gastroenterology and Hepatology, VA Loma Linda Healthcare System, Loma Linda, California; Loma Linda University, Loma Linda, California; Department of Internal Medicine, University of California, Riverside, Riverside, California
| | - HoChong Gilles
- Division of Gastroenterology and Hepatology, Central Virginia VA Healthcare System, Richmond, Virginia
| | - Anand S Shah
- Division of Gastroenterology, Joseph Maxwell Cleland Atlanta VA Medical Center, Decatur, Georgia; Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia
| | | | - Puneet Puri
- Division of Gastroenterology and Hepatology, Central Virginia VA Healthcare System, Richmond, Virginia; Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia
| | - Janice Jou
- VA Portland Healthcare System, Portland, Oregon; Division of Gastroenterology and Hepatology, Department of Medicine, Oregon Health & Science University, Portland, Oregon
| | - Khurram Mazhar
- VA North Texas Health Care System, Dallas, Texas; Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Jason A Dominitz
- VA Puget Sound Health Care System, Seattle, Washington; Division of Gastroenterology, University of Washington School of Medicine, Seattle, Washington
| | - Jennifer Anwar
- Gastroenterology Section, VA Long Beach Healthcare System, Long Beach, California
| | - Timothy R Morgan
- Gastroenterology Section, VA Long Beach Healthcare System, Long Beach, California; Division of Gastroenterology, Department of Medicine, University of California, Irvine, California
| | - George N Ioannou
- VA Puget Sound Health Care System, Seattle, Washington; Division of Gastroenterology, University of Washington School of Medicine, Seattle, Washington
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12
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Koo E, Singal AG. Hepatocellular Carcinoma Surveillance: Evidence-Based Tailored Approach. Surg Oncol Clin N Am 2024; 33:13-28. [PMID: 37945138 DOI: 10.1016/j.soc.2023.06.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2023]
Abstract
Hepatocellular carcinoma (HCC) surveillance is recommended by professional society guidelines given a consistent association with reduced HCC-related mortality. HCC surveillance should be performed using semiannual abdominal ultrasound and alpha-fetoprotein, although this combination has suboptimal sensitivity and can miss more than one-third of HCC at an early stage. There are promising emerging blood-based and imaging-based strategies, including abbreviated MRI and biomarker panels; however, these require further validation before routine use in clinical practice. HCC surveillance is underused in clinical practice due to patient-related and provider-related barriers, highlighting a need for interventions to improve surveillance utilization in clinical practice.
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Affiliation(s)
- Eden Koo
- 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; Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, 5959 Harry Hines Boulevard, POB 1, Suite 420, Dallas, TX 75390-8887, USA.
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13
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Do WL, Wang L, Forgues M, Liu J, Rabibhadana S, Pupacdi B, Zhao Y, Gholian H, Bhudhisawasdi V, Pairojkul C, Sukeepaisarnjaroen W, Pugkhem A, Luvira V, Lertprasertsuke N, Chotirosniramit A, Auewarakul CU, Ungtrakul T, Sricharunrat T, Sangrajrang S, Phornphutkul K, Budhu A, Harris CC, Mahidol C, Ruchirawat M, Wang XW. Pan-viral serology uncovers distinct virome patterns as risk predictors of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Cell Rep Med 2023; 4:101328. [PMID: 38118412 PMCID: PMC10772458 DOI: 10.1016/j.xcrm.2023.101328] [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: 03/13/2023] [Revised: 07/31/2023] [Accepted: 11/17/2023] [Indexed: 12/22/2023]
Abstract
This study evaluates the pan-serological profiles of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) compared to several diseased and non-diseased control populations to identify risk factors and biomarkers of liver cancer. We used phage immunoprecipitation sequencing, an anti-viral antibody screening method using a synthetic-phage-displayed human virome epitope library, to screen patient serum samples for exposure to over 1,280 strains of pathogenic and non-pathogenic viruses. Using machine learning methods to develop an HCC or iCCA viral score, we discovered that both viral scores were positively associated with several liver function markers in two separate at-risk populations independent of viral hepatitis status. The HCC score predicted all-cause mortality over 8 years in patients with chronic liver disease at risk of HCC, while the viral hepatitis status was not predictive of survival. These results suggest that non-hepatitis viral infections may contribute to HCC and iCCA development and could be biomarkers in at-risk populations.
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Affiliation(s)
- Whitney L Do
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
| | - Limin Wang
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
| | - Marshonna Forgues
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
| | - Jinping Liu
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
| | | | | | - Yongmei Zhao
- Office of Science and Technology Resources, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
| | - Heelah Gholian
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
| | | | | | | | | | - Vor Luvira
- Khon Kaen University, Khon Kaen, Thailand
| | | | | | | | | | | | | | | | - Anuradha Budhu
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA; Liver Cancer Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
| | - Curtis C Harris
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
| | | | - Mathuros Ruchirawat
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA; Center of Excellence on Environmental Health and Toxicology, Office of Higher Education Commission, Ministry of Education, Bangkok, Thailand.
| | - Xin Wei Wang
- Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA; Liver Cancer Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
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14
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Kanwal F, Khaderi S, Singal AG, Marrero JA, Asrani SK, Amos CI, Thrift AP, Kramer JR, Yu X, Cao Y, Luster M, Al-Sarraj A, Ning J, El-Serag HB. Risk Stratification Model for Hepatocellular Cancer in Patients With Cirrhosis. Clin Gastroenterol Hepatol 2023; 21:3296-3304.e3. [PMID: 37390101 PMCID: PMC10661677 DOI: 10.1016/j.cgh.2023.04.019] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 04/07/2023] [Accepted: 04/13/2023] [Indexed: 07/02/2023]
Abstract
BACKGROUND & AIMS The available risk stratification indices for hepatocellular cancer (HCC) have limited applicability. We developed and externally validated an HCC risk stratification index in U.S. cohorts of patients with cirrhosis. METHODS We used data from 2 prospective U.S. cohorts to develop the risk index. Patients with cirrhosis were enrolled from 8 centers and followed until development of HCC, death, or December 31, 2021. We identified an optimal set of predictors with the highest discriminatory ability (C-index) for HCC. The predictors were refit using competing risk regression and its predictive performance was evaluated using the area under the receiver-operating characteristic curve (AUROC). External validation was performed in a cohort of 21,550 patients with cirrhosis seen in the U.S Veterans Affairs system between 2018 and 2019 with follow-up through 2021. RESULTS We developed the model in 2431 patients (mean age 60 years, 31% women, 24% cured hepatitis C, 16% alcoholic liver disease, and 29% nonalcoholic fatty liver disease). The selected model had a C-index of 0.77 (95% confidence interval [CI], 0.73-0.81), and the predictors were age, sex, smoking, alcohol use, body mass index, etiology, α-fetoprotein, albumin, alanine aminotransferase, and platelet levels. The AUROCs were 0.75 (95% CI, 0.65-0.85) at 1 year and 0.77 (95% CI, 0.71-0.83) at 2 years, and the model was well calibrated. In the external validation cohort, the AUROC at 2 years was 0.70 with excellent calibration. CONCLUSION The risk index, including objective and routinely available risk factors, can differentiate patients with cirrhosis who will develop HCC and help guide discussions regarding HCC surveillance and prevention. Future studies are needed for additional external validation and refinement of risk stratification.
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Affiliation(s)
- Fasiha Kanwal
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas; Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, Texas; VA HSR&D Center for Innovatio ns in Quality, Effectiveness, and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas.
| | - Saira Khaderi
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas
| | - Amit G Singal
- Division of Digestive and Liver Diseases, Department of Medicine, UT Southwestern Medical Center, Dallas, Texas
| | - Jorge A Marrero
- Division of Digestive and Liver Diseases, Department of Medicine, UT Southwestern Medical Center, Dallas, Texas
| | - Sumeet K Asrani
- Division of Gastroenterology, Department of Medicine, Baylor University Medical Center, Dallas, Texas
| | - Christopher I Amos
- Section of Epidemiology, Department of Medicine, Baylor College of Medicine, Houston, Texas
| | - Aaron P Thrift
- Section of Epidemiology, Department of Medicine, Baylor College of Medicine, Houston, Texas
| | - Jennifer R Kramer
- Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, Texas; VA HSR&D Center for Innovatio ns in Quality, Effectiveness, and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
| | - Xian Yu
- Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, Texas; VA HSR&D Center for Innovatio ns in Quality, Effectiveness, and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
| | - Yumei Cao
- Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, Texas; VA HSR&D Center for Innovatio ns in Quality, Effectiveness, and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
| | - Michelle Luster
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas
| | - Abeer Al-Sarraj
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas; Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, Texas; VA HSR&D Center for Innovatio ns in Quality, Effectiveness, and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
| | - Jing Ning
- Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Hashem B El-Serag
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas; Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, Texas; VA HSR&D Center for Innovatio ns in Quality, Effectiveness, and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas.
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15
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Thörn R, Hemmingsson O, Danielsson Borssén Å, Werner M, Karling P, Wixner J. Improved Survival in At-Risk Patients Undergoing Surveillance for Hepatocellular Carcinoma - A Nationwide Swedish Register-Based Study. J Hepatocell Carcinoma 2023; 10:1573-1586. [PMID: 37753268 PMCID: PMC10518262 DOI: 10.2147/jhc.s420130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Accepted: 08/24/2023] [Indexed: 09/28/2023] Open
Abstract
Purpose Surveillance for hepatocellular carcinoma (HCC) is recommended in at-risk patients, but its effectiveness in Western populations has been questioned. The purpose was to evaluate the effect of surveillance in patients with HCC in a Northern European setting. Patients and Methods Data on patients diagnosed with HCC between 2009 and 2019 were collected from the nationwide Swedish National Registry for Tumors of the Liver and Bile Ducts (SweLiv). Patients who had undergone HCC surveillance were compared to those who had not (but had an obvious indication for surveillance, ie, liver cirrhosis or hepatic porphyria and an age of ≥50 years) regarding etiology, tumor burden, presence of extrahepatic spread, treatment and lead-time adjusted overall survival. Results A total of 4979 patients with index HCC were identified and information regarding surveillance was available in 4116 patients. Among these, 1078 had got their HCC diagnosis during surveillance, whereas 1647 had been diagnosed without surveillance despite a presumed indication. The most common underlying etiologies for HCC were hepatitis C (28.2%) and alcoholic liver disease (26.9%), and 94.8% had cirrhosis. The surveillance cohort more frequently met the University of California San Francisco-criteria (79% vs 53%, p <0.001), more often received a potentially curative treatment (62% vs 28%, p <0.001) and had less extrahepatic spread (7.6% vs 22.4% p <0.001). After adjustment for lead-time bias (sojourn time of 270 days), the surveillance group had a significantly longer estimated median survival time than the non-surveillance group (34 months vs 11 months, p <0.001). A multivariable cox regression analysis showed an adjusted hazard ratio of 0.59 (95% CI 0.51-0.67) in favor of surveillance. Conclusion Surveillance for HCC in at-risk patients is associated with diagnosis at an earlier tumor stage, treatment with curative intent and with improved lead-time adjusted overall survival. These findings encourage HCC surveillance of at-risk patients also in a Western population.
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Affiliation(s)
- Richard Thörn
- Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | - Oskar Hemmingsson
- Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden
- Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden
| | | | - Mårten Werner
- Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | - Pontus Karling
- Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | - Jonas Wixner
- Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
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16
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Lee RM, Russell MC. Is Screening for Hepatocellular Carcinoma Effective? Adv Surg 2023; 57:73-86. [PMID: 37536863 DOI: 10.1016/j.yasu.2023.03.003] [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: 08/05/2023]
Abstract
Hepatocellular carcinoma occurs primarily in patients with cirrhosis and is an important cause of cancer death. Screening for hepatocellular carcinoma every 6 months with ultrasound with or without alpha fetoprotein measurement is recommended by multiple professional societies. There are no randomized controlled trials in patients with cirrhosis documenting the effectiveness of screening in improving survival, however, making screening controversial. There are multiple retrospective and cohort studies, as well as pooled analyses that do show an association of screening with earlier stage at diagnosis, increased receipt of curative intent treatment, and improved overall survival. Though these studies are limited by lead and length time biases, they make compelling arguments in favor of screening. Additional research into barriers to receiving screening, barriers to receiving treatment, and the optimal screening modalities given the shift of cirrhosis etiology in the United States are needed to further improve patient outcomes.
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Affiliation(s)
- Rachel M Lee
- Department of Surgery, Emory University, Atlanta, GA, USA
| | - Maria C Russell
- Department of Surgery, Division of Surgical Oncology, Emory University, Emory University Hospital Midtown, 9th Floor MOT, 550 Peachtree Street, Atlanta, GA 30308, USA.
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17
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King WW, Richhart R, Culpepper T, Mota M, Banerjee D, Ismael M, Chakraborty J, Ladna M, Khan W, Ruiz N, Wilson J, Altshuler E, Clark V, Cabrera R. Adherence to guideline-directed hepatocellular carcinoma screening: A single-center US experience. World J Hepatol 2023; 15:410-418. [PMID: 37034234 PMCID: PMC10075011 DOI: 10.4254/wjh.v15.i3.410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Revised: 01/16/2023] [Accepted: 02/21/2023] [Indexed: 03/22/2023] Open
Abstract
BACKGROUND The American Association for the Study of Liver Disease recommends screening patients with cirrhosis for hepatocellular carcinoma (HCC) using imaging with or without alpha-fetoprotein every six months. Unfortunately, screening rates remain inadequate.
AIM To assess root causes of screening failure in a subspecialty hepatology clinic.
METHODS The authors identified patients with cirrhosis seen in a subspecialty hepatology clinic and determined whether they underwent appropriate screening, defined as two cross-sectional images between five and seven months apart. The authors characterized the primary driver of screening failure. Finally, other hepatologists were surveyed to determine provider perceptions of screening failure causes.
RESULTS 1034 patients were identified with an average age of 61 years and a mean MELD of 8.1 ± 3.8. Hepatitis C virus was the most common cirrhosis etiology. 489 (47%) underwent appropriate screening. No demographic or clinical differences were detected between those who underwent appropriate screening and those who did not. The most common etiologies of screening failure, in descending order, were: radiology unable to schedule timely imaging, provider did not order imaging, patient canceled follow up appointment, appointments scheduled too far apart, lost to follow up, no-show to radiology appointment, and provider canceled appointment. Hepatologists surveyed believed the most common cause of screening failure was no-show to radiology.
CONCLUSION Rates of screening were poor even in a subspecialty hepatology clinic. Screening failure was mostly due to systemic factors such as radiology availability and time between hepatology appointments rather than individual error.
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Affiliation(s)
- William W King
- Department of Medicine, University of Florida, Gainesville, FL 32610, United States
| | - Raymond Richhart
- Department of Medicine, University of Florida, Gainesville, FL 32610, United States
| | - Tyler Culpepper
- Department of Medicine, University of Florida, Gainesville, FL 32610, United States
| | - Maneola Mota
- Department of Gastroenterology, University of Florida, Gainesville, FL 32610, United States
| | - Debdeep Banerjee
- Department of Medicine, University of Florida, Gainesville, FL 32610, United States
| | - Media Ismael
- Department of Gastroenterology, University of Florida, Gainesville, FL 32610, United States
| | - Joydeep Chakraborty
- Department of Gastroenterology, University of Florida, Gainesville, FL 32610, United States
| | - Michael Ladna
- Department of Hospital Medicine, University of Florida, Gainesville, FL 32610, United States
| | - Walid Khan
- Department of Hospital Medicine, University of Florida, Gainesville, FL 32610, United States
| | - Nicole Ruiz
- Department of Medicine, University of Florida, Gainesville, FL 32610, United States
| | - Jake Wilson
- Department of Medicine, University of Florida, Gainesville, FL 32610, United States
| | - Ellery Altshuler
- Department of Medicine, University of Florida, Gainesville, FL 32610, United States
| | - Virginia Clark
- Department of Gastroenterology, University of Florida, Gainesville, FL 32610, United States
| | - Roniel Cabrera
- Department of Gastroenterology, University of Florida, Gainesville, FL 32610, United States
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18
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Chu J, Cholankeril G, Yu X, Rana A, Natarajan Y, El-Serag HB, Kramer J, Kanwal F. Clinical Course and Outcomes of Patients with Nonalcoholic Fatty Liver Disease-Related Hepatocellular Cancer (NAFLD-HCC). Dig Dis Sci 2023; 68:1060-1070. [PMID: 35759159 PMCID: PMC9792631 DOI: 10.1007/s10620-022-07565-x] [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: 12/30/2021] [Accepted: 05/10/2022] [Indexed: 12/30/2022]
Abstract
BACKGROUND & AIMS Among etiologies for hepatocellular (HCC), nonalcoholic fatty liver disease (NAFLD) carries a high risk of competing non-cancer mortality. The effect of cancer and non-cancer factors on risk of death after NAFLD-HCC diagnosis remains unclear. We aimed to evaluate the role of non-cancer mortality with NAFLD-HCC. METHODS Using a retrospective cohort of patients with NAFLD diagnosed at 130 facilities in the Veterans Administration, we identified patients with incident HCC diagnosed between January 1, 2005 and June 30, 2018. We determined cause of death as HCC-related, non-HCC liver-related, and non-liver-related after HCC diagnosis. We used Cox proportional hazards regression models to evaluate the effect of clinical factors on cause-specific mortality after NAFLD-HCC diagnosis. RESULTS We identified 776 patients with incident HCC. Mean age at HCC diagnosis was 70.1 year, 22.2% had Barcelona Clinic Liver Cancer (BCLC) stage 0-A, and 67.0% had more than one comorbidity. 1- and 3-year mortality rates were 47.0% and 69.6%, respectively. Most deaths (72.2% at 3 years) were attributable to HCC. In HCC patients who received curative treatment, non-cancer mortality accounted for 40% of all deaths between 3 and 5 years after treatment. Poor performance status (ECOG 3/4, HR 5.03, 95% CI: 2.59-9.77) and older age (65-75, HR 1.94, 95% CI: 1.06-3.54) were strongly associated with non-cancer mortality. CONCLUSION Although most patients with NAFLD-HCC die of HCC, non-cancer mortality represents a clinically meaningful competing event for patients receiving curative treatment, underscoring the importance of assessing and managing risk factors of non-cancer morbidity and mortality. TRIAL AND REGISTRATION N/A.
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Affiliation(s)
- Jinna Chu
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - George Cholankeril
- Liver Center, Division of Abdominal Transplantation, Michael E DeBakey Department of General Surgery, Baylor College of Medicine, Houston, TX, USA
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, 2002 Holcombe Boulevard (152), Houston, TX, USA
| | - Xian Yu
- Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA
| | - Abbas Rana
- Liver Center, Division of Abdominal Transplantation, Michael E DeBakey Department of General Surgery, Baylor College of Medicine, Houston, TX, USA
| | - Yamini Natarajan
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, 2002 Holcombe Boulevard (152), Houston, TX, USA
- Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA
| | - Hashem B El-Serag
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, 2002 Holcombe Boulevard (152), Houston, TX, USA
- Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA
| | - Jennifer Kramer
- Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA
| | - Fasiha Kanwal
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, 2002 Holcombe Boulevard (152), Houston, TX, USA.
- Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA.
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19
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Vaz J, Strömberg U, Midlöv P, Eriksson B, Buchebner D, Hagström H. Unrecognized liver cirrhosis is common and associated with worse survival in hepatocellular carcinoma: A nationwide cohort study of 3473 patients. J Intern Med 2023; 293:184-199. [PMID: 36166276 PMCID: PMC10091698 DOI: 10.1111/joim.13570] [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] [Indexed: 01/05/2023]
Abstract
BACKGROUND Data on unrecognized liver cirrhosis in patients with hepatocellular carcinoma (HCC) are derived mainly from cohorts with a risk of selection bias. OBJECTIVES In a population-based cohort study we aimed to determine the proportion, characteristics, and prognosis of HCC in patients with unrecognized cirrhosis. METHODS Using the Swedish quality register for liver cancer and other nationwide registers, we identified all adults with HCC in Sweden between 2012 and 2018 (n = 3,473). RESULTS The final study cohort comprised 2670 patients with established cirrhosis, of which 1033 (39%) had unrecognized cirrhosis at HCC diagnosis. These patients were more often male, older, and had larger tumors, multinodular cancer, portal vein thrombosis, and extrahepatic metastasis compared to patients with known cirrhosis with HCC and under surveillance (34%). Compared to surveilled patients, those with unrecognized cirrhosis had worse median survival (0.89 years, 95% confidence interval [CI] = 0.78-1.01 vs. 3.79 years, 95%CI = 3.19-4.39), and an adjusted hazard ratio of 2.36 (95%CI = 2.09-2.66). Patients with cirrhosis but not under surveillance (27%) and patients with unrecognized cirrhosis had similar characteristics, such as equal proportions diagnosed at late stage (79%). CONCLUSIONS Cirrhosis is often not recognized in patients with HCC. Unrecognized cirrhosis is associated with more advanced HCC at diagnosis and a worse prognosis. More efforts are needed to diagnose cirrhosis at an earlier stage.
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Affiliation(s)
- Juan Vaz
- Department of Clinical Sciences in Malmö, Center for Primary Health Care Research, Lund University, Malmö, Sweden.,Department of Internal Medicine, Halland Hospital Halmstad, Halmstad, Sweden
| | - Ulf Strömberg
- Department of Research and Development, Region Halland, Halmstad, Sweden.,Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Patrik Midlöv
- Department of Clinical Sciences in Malmö, Center for Primary Health Care Research, Lund University, Malmö, Sweden
| | - Berne Eriksson
- Department of Research and Development, Region Halland, Halmstad, Sweden.,Krefting Research Center, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
| | - David Buchebner
- Department of Internal Medicine, Halland Hospital Halmstad, Halmstad, Sweden
| | - Hannes Hagström
- Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.,Division of Hepatology, Department of Upper GI Diseases, Karolinska University Hospital, Stockholm, Sweden.,Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
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20
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Cernea S, Onișor D. Screening and interventions to prevent nonalcoholic fatty liver disease/nonalcoholic steatohepatitis-associated hepatocellular carcinoma. World J Gastroenterol 2023; 29:286-309. [PMID: 36687124 PMCID: PMC9846941 DOI: 10.3748/wjg.v29.i2.286] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Revised: 11/06/2022] [Accepted: 12/21/2022] [Indexed: 01/06/2023] Open
Abstract
Liver cancer is the sixth most commonly diagnosed cancer worldwide, with hepatocellular carcinoma (HCC) comprising most cases. Besides hepatitis B and C viral infections, heavy alcohol use, and nonalcoholic steatohepatitis (NASH)-associated advanced fibrosis/cirrhosis, several other risk factors for HCC have been identified (i.e. old age, obesity, insulin resistance, type 2 diabetes). These might in fact partially explain the occurrence of HCC in non-cirrhotic patients without viral infection. HCC surveillance through effective screening programs is still an unmet need for many nonalcoholic fatty liver disease (NAFLD) patients, and identification of pre-cirrhotic individuals who progress to HCC represents a substantial challenge in clinical practice at the moment. Patients with NASH-cirrhosis should undergo systematic HCC surveillance, while this might be considered in patients with advanced fibrosis based on individual risk assessment. In this context, interventions that potentially prevent NAFLD/ NASH-associated HCC are needed. This paper provided an overview of evidence related to lifestyle changes (i.e. weight loss, physical exercise, adherence to healthy dietary patterns, intake of certain dietary components, etc.) and pharmacological interventions that might play a protective role by targeting the underlying causative factors and pathogenetic mechanisms. However, well-designed prospective studies specifically dedicated to NAFLD/NASH patients are still needed to clarify the relationship with HCC risk.
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Affiliation(s)
- Simona Cernea
- Department M3/Internal Medicine I, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, Târgu Mureş 540139, Romania
- Diabetes, Nutrition and Metabolic Diseases Outpatient Unit, Emergency County Clinical Hospital, Târgu Mureş 540136, Romania
| | - Danusia Onișor
- Department ME2/Internal Medicine VII, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureş, Târgu Mureş 540139, Romania
- Gastroenterology Department, Mureș County Clinical Hospital, Târgu Mureș 540072, Romania
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21
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Kramer JR, Cao Y, Li L, Smith D, Chhatwal J, El-Serag HB, Kanwal F. Longitudinal Associations of Risk Factors and Hepatocellular Carcinoma in Patients With Cured Hepatitis C Virus Infection. Am J Gastroenterol 2022; 117:1834-1844. [PMID: 36327437 PMCID: PMC9641546 DOI: 10.14309/ajg.0000000000001968] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Accepted: 08/03/2022] [Indexed: 11/06/2022]
Abstract
INTRODUCTION There are limited data on the effect and evolution of risk factors for hepatocellular carcinoma (HCC) in patients with virologically cured hepatitis C virus (HCV) infection. METHODS We conducted a retrospective cohort study of patients with HCV who achieved sustained virological response with direct-acting antivirals from 130 Veterans Administration hospitals during 2014-2018, followed through 2021. Cox proportional hazards models were constructed at 3 landmark times (baseline and 12 and 24 months after sustained virological response) to examine associations between demographic, clinical, and behavioral factors and HCC risk, stratified by cirrhosis status. RESULTS Among 92,567 patients (32% cirrhosis), 3,247 cases of HCC were diagnosed during a mean follow-up of 2.5 years. In patients with cirrhosis, male sex (hazard ratios [HR]: 1.89, 1.93, and 1.99), cirrhosis duration ≥5 years (HR: 1.71, 1.79, and 1.34), varices (HR: 1.73, 1.60, and 1.56), baseline albumin (HR: 0.48, 0.47, and 0.49), and change in albumin (HR: 0.82 and 0.90) predicted HCC risk at each landmark time. HCV genotype 3, previous treatment, bilirubin, smoking, and race influenced HCC risk at baseline, but their effects attenuated over time. In patients without cirrhosis, diabetes (HR: 1.54, 1.42, and 1.47) and hypertension (HR: 1.59, 1.65, and 1.74) were associated with HCC risk at all landmark times. Changes in fibrosis-4 scores over time were associated with HCC risk both in patients with and without cirrhosis. DISCUSSION Risk factors for HCC were different in patients with and without cirrhosis and some also evolved during follow-up. These factors can help with risk stratification and HCC surveillance decisions in patients with cured HCV.
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Affiliation(s)
- Jennifer R. Kramer
- Center for Innovations in Quality, Effectiveness and Safety
(IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
- Section of Health Services Research, Department of
Medicine, Baylor College of Medicine, Houston, Texas
| | - Yumei Cao
- Center for Innovations in Quality, Effectiveness and Safety
(IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
- Section of Health Services Research, Department of
Medicine, Baylor College of Medicine, Houston, Texas
| | - Liang Li
- Department of Biostatistics, University of Texas MD
Anderson Cancer Center, Houston, Texas
| | - Donna Smith
- Center for Innovations in Quality, Effectiveness and Safety
(IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
| | - Jagpreet Chhatwal
- Massachusetts General Hospital Institute for Technology
Assessment, Harvard Medical School, Boston, Massachusetts
| | - Hashem B. El-Serag
- Center for Innovations in Quality, Effectiveness and Safety
(IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
- Section of Gastroenterology and Hepatology, Department of
Medicine, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical
Center, Houston, Texas
| | - Fasiha Kanwal
- Center for Innovations in Quality, Effectiveness and Safety
(IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
- Section of Gastroenterology and Hepatology, Department of
Medicine, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical
Center, Houston, Texas
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22
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Kim BH, Cho Y, Park JW. Surveillance for hepatocellular carcinoma: It is time to move forward. Clin Mol Hepatol 2022; 28:810-813. [PMID: 36064304 PMCID: PMC9597219 DOI: 10.3350/cmh.2022.0257] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 08/30/2022] [Indexed: 01/05/2023] Open
Affiliation(s)
- Bo Hyun Kim
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
| | - Joong-Won Park
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
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23
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Roeb E, Canbay A, Bantel H, Bojunga J, de Laffolie J, Demir M, Denzer UW, Geier A, Hofmann WP, Hudert C, Karlas T, Krawczyk M, Longerich T, Luedde T, Roden M, Schattenberg J, Sterneck M, Tannapfel A, Lorenz P, Tacke F. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:1346-1421. [PMID: 36100202 DOI: 10.1055/a-1880-2283] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- E Roeb
- Gastroenterologie, Medizinische Klinik II, Universitätsklinikum Gießen und Marburg, Gießen, Deutschland
| | - A Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - H Bantel
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - J Bojunga
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin., Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - J de Laffolie
- Allgemeinpädiatrie und Neonatologie, Zentrum für Kinderheilkunde und Jugendmedizin, Universitätsklinikum Gießen und Marburg, Gießen, Deutschland
| | - M Demir
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum und Campus Charité Mitte, Berlin, Deutschland
| | - U W Denzer
- Klinik für Gastroenterologie und Endokrinologie, Universitätsklinikum Gießen und Marburg, Marburg, Deutschland
| | - A Geier
- Medizinische Klinik und Poliklinik II, Schwerpunkt Hepatologie, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - W P Hofmann
- Gastroenterologie am Bayerischen Platz - Medizinisches Versorgungszentrum, Berlin, Deutschland
| | - C Hudert
- Klinik für Pädiatrie m. S. Gastroenterologie, Nephrologie und Stoffwechselmedizin, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - T Karlas
- Klinik und Poliklinik für Onkologie, Gastroenterologie, Hepatologie, Pneumologie und Infektiologie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - M Krawczyk
- Klinik für Innere Medizin II, Gastroent., Hepat., Endokrin., Diabet., Ern.med., Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - T Longerich
- Pathologisches Institut, Universitätsklinikum Heidelberg, Heidelberg, Deutschland
| | - T Luedde
- Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland
| | - M Roden
- Klinik für Endokrinologie und Diabetologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland
| | - J Schattenberg
- I. Medizinische Klinik und Poliklinik, Universitätsmedizin Mainz, Mainz, Deutschland
| | - M Sterneck
- Klinik für Hepatobiliäre Chirurgie und Transplantationschirurgie, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - A Tannapfel
- Institut für Pathologie, Ruhr-Universität Bochum, Bochum, Deutschland
| | - P Lorenz
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), Berlin, Deutschland
| | - F Tacke
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum und Campus Charité Mitte, Berlin, Deutschland
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24
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Authors, Collaborators:. Updated S2k Clinical Practice Guideline on Non-alcoholic Fatty Liver Disease (NAFLD) issued by the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS) - April 2022 - AWMF Registration No.: 021-025. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:e733-e801. [PMID: 36100201 DOI: 10.1055/a-1880-2388] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
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25
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Khan A, Zhang X. Function of the Long Noncoding RNAs in Hepatocellular Carcinoma: Classification, Molecular Mechanisms, and Significant Therapeutic Potentials. Bioengineering (Basel) 2022; 9:406. [PMID: 36004931 PMCID: PMC9405066 DOI: 10.3390/bioengineering9080406] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2022] [Revised: 08/15/2022] [Accepted: 08/16/2022] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common and serious type of primary liver cancer. HCC patients have a high death rate and poor prognosis due to the lack of clear signs and inadequate treatment interventions. However, the molecular pathways that underpin HCC pathogenesis remain unclear. Long non-coding RNAs (lncRNAs), a new type of RNAs, have been found to play important roles in HCC. LncRNAs have the ability to influence gene expression and protein activity. Dysregulation of lncRNAs has been linked to a growing number of liver disorders, including HCC. As a result, improved understanding of lncRNAs could lead to new insights into HCC etiology, as well as new approaches for the early detection and treatment of HCC. The latest results with respect to the role of lncRNAs in controlling multiple pathways of HCC were summarized in this study. The processes by which lncRNAs influence HCC advancement by interacting with chromatin, RNAs, and proteins at the epigenetic, transcriptional, and post-transcriptional levels were examined. This critical review also highlights recent breakthroughs in lncRNA signaling pathways in HCC progression, shedding light on the potential applications of lncRNAs for HCC diagnosis and therapy.
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Affiliation(s)
| | - Xiaobo Zhang
- College of Life Sciences, Zhejiang University, Hangzhou 310058, China
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26
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Parikh ND, Tayob N, Al-Jarrah T, Kramer J, Melcher J, Smith D, Marquardt P, Liu PH, Tang R, Kanwal F, Singal AG. Barriers to Surveillance for Hepatocellular Carcinoma in a Multicenter Cohort. JAMA Netw Open 2022; 5:e2223504. [PMID: 35867057 PMCID: PMC9308050 DOI: 10.1001/jamanetworkopen.2022.23504] [Citation(s) in RCA: 58] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Accepted: 06/02/2022] [Indexed: 01/07/2023] Open
Abstract
Importance Hepatocellular carcinoma (HCC) surveillance is underused in clinical practice, which may be owing to patient and clinician barriers. Objective To characterize HCC surveillance barriers and associations with clinical outcomes in a multicenter cohort of patients with cirrhosis. Design, Setting, and Participants This retrospective, multicenter cohort study included 5 medical centers in the United States. Patients with cirrhosis and newly diagnosed HCC treated from 2014 to 2018 were included. Data were analyzed from June 2021 to February 2022. Exposure Surveillance completion in the 36-month period prior to HCC diagnosis. Main Outcomes and Measures Surveillance receipt was classified as semiannual, annual, or no surveillance. Multivariable logistic regression analysis was used to identify factors associated with semiannual surveillance. We conducted multivariable logistic and Cox regression analyses to characterize associations between surveillance completion with curative treatment and overall survival. Results A total 629 eligible patients (median [IQR] age, 63.6 [56.2-71.0] years; 491 [78.1%] men) were assessed, including 7 American Indian or Alaska Native patients (1.1%), 14 Asian patients (2.2), 176 Black patients (28.0%), 86 Hispanic patients (13.1%), and 340 White patients (54.1%). Nearly two-thirds of the cohort had no surveillance prior to HCC diagnosis (mean [range by site] 63.7% [37.9%-80.4%]), with a mean (range by site) of 14.0% (5.3%-33.3%) of patients having received semiannual surveillance and 22.3% (14.3%-28.8%) of patients having received annual surveillance. The most common reasons for no surveillance were lack of surveillance orders or nonadherence (mean [range by site], 82.4% [66.7%-92.4%], although a mean (range by site) of 17.6% (10.2%-22.1%) of patients had unrecognized cirrhosis at HCC presentation. Semiannual surveillance was associated with hepatitis B infection (odds ratio [OR], 3.06 [95% CI, 1.24-7.23]) and inversely associated with Black race (OR, 0.41 [95% CI, 0.20-0.80]) and lack of cirrhosis recognition (OR, 0.14 [95% CI, 0.02-0.46]). Semiannual HCC surveillance was significantly associated with curative treatment receipt (OR, 2.73 [95% CI, 1.60-4.70]) but not overall survival (HR, 0.81 [95% CI, 0.55-1.18]). Conclusions and Relevance In this cohort study of patients with cirrhosis, HCC surveillance was underused in more than 80% of patients and associated with failures across the screening process. Dedicated programs to improve cirrhosis detection and HCC surveillance attainment are needed.
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Affiliation(s)
- Neehar D. Parikh
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor
| | - Nabihah Tayob
- Department of Biostatistics, Dana Farber Cancer Center, Boston, Massachusetts
| | - Taim Al-Jarrah
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor
| | - Jennifer Kramer
- Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
- Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas
| | - Jennifer Melcher
- Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
- Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas
| | - Donna Smith
- Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
- Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas
| | - Patrick Marquardt
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas
| | - Po-Hong Liu
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas
| | - Runlong Tang
- Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Fasiha Kanwal
- Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
- Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas
- Division of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas
| | - Amit G. Singal
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas
- Harold C. Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas
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27
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Singal AG, Zhang E, Narasimman M, Rich NE, Waljee AK, Hoshida Y, Yang JD, Reig M, Cabibbo G, Nahon P, Parikh ND, Marrero JA. HCC surveillance improves early detection, curative treatment receipt, and survival in patients with cirrhosis: A meta-analysis. J Hepatol 2022; 77:128-139. [PMID: 35139400 PMCID: PMC9232881 DOI: 10.1016/j.jhep.2022.01.023] [Citation(s) in RCA: 236] [Impact Index Per Article: 78.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Revised: 01/20/2022] [Accepted: 01/24/2022] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS There is controversy regarding the overall value of hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis given the lack of data from randomized-controlled trials. To address this issue, we conducted a systematic review and meta-analysis of cohort studies evaluating the benefits and harms of HCC surveillance in patients with cirrhosis. METHODS We performed a search of the Medline and EMBASE databases and national meeting abstracts from January 2014 through July 2020 for studies reporting early-stage HCC detection, curative treatment receipt, or overall survival, stratified by HCC surveillance status, among patients with cirrhosis. Pooled risk ratios (RRs) and hazard ratios, according to HCC surveillance status, were calculated for each outcome using the DerSimonian and Laird method for random effects models. RESULTS We identified 59 studies including 145,396 patients with HCC, which was detected by surveillance in 41,052 (28.2%) cases. HCC surveillance was associated with improved early-stage detection (RR 1.86, 95% CI 1.73-1.98; I2 = 82%), curative treatment receipt (RR 1.83, 95% CI 1.69-1.97; I2 = 75%), and overall survival (hazard ratio 0.67, 95% CI 0.61-0.72; I2 = 78%) after adjusting for lead-time bias; however, there was notable heterogeneity in all pooled estimates. Four studies examined surveillance-related physical harms due to false positive or indeterminate surveillance results, but no studies examined potential financial or psychological harms. The proportion of patients experiencing surveillance-related physical harms ranged from 8.8% to 27.5% across studies, although most harms were mild in severity. CONCLUSION HCC surveillance is associated with improved early detection, curative treatment receipt, and survival in patients with cirrhosis, although there was heterogeneity in pooled estimates. Available data suggest HCC surveillance is of high value in patients with cirrhosis, although continued rigorous studies evaluating benefits and harms are still needed. LAY SUMMARY There has been ongoing debate about the overall value of hepatocellular carcinoma (HCC) screening in patients with cirrhosis given the lack of data from randomized-controlled trials. In a systematic review of contemporary cohort studies, we found that HCC screening is associated with improved early detection, curative treatment receipt, and survival in patients with cirrhosis, although there were fewer data quantifying potential screening-related harms. Available data suggest HCC screening is of high value in patients with cirrhosis, although continued studies evaluating benefits and harms are still needed.
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Affiliation(s)
- Amit G Singal
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, United States.
| | - Emily Zhang
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, United States
| | - Manasa Narasimman
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, United States
| | - Nicole E Rich
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, United States
| | - Akbar K Waljee
- Department of Internal Medicine, University of Michigan, Ann Arbor MI, United States
| | - Yujin Hoshida
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, United States
| | - Ju Dong Yang
- Karsh Division of Gastroenterology and Hepatology, Comprehensive Transplant Center, Samuel Oschin Comprehensive Cancer Institute, Cedars Sinai, Los Angeles, CA, United States
| | - Maria Reig
- Barcelona Clinic Liver Cancer (BCLC) Group, Hospital Clinic de Barcelona, CIBEREEHD, Barcelona University, Barcelona, Spain
| | - Giuseppe Cabibbo
- Section of Gastroenterology & Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Pierre Nahon
- AP-HP, Hôpital Avicenne, Liver Unit, Université Sorbonne Paris Nord, Bobigny, France; Inserm, UMR-1138 Université de Paris, Paris, France
| | - Neehar D Parikh
- Department of Internal Medicine, University of Michigan, Ann Arbor MI, United States
| | - Jorge A Marrero
- Department of Internal Medicine, University of Pennsylvania, Philadelphia PA, United States
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28
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Mo C, Wu J, Sui J, Deng Y, Li M, Cao Z, Hu Z, Huang J, Li S. Long non-coding RNA LINC01793 as a potential diagnostic biomarker of hepatitis B virus-related hepatocellular carcinoma. Clin Biochem 2022; 108:56-62. [PMID: 35760369 DOI: 10.1016/j.clinbiochem.2022.06.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Revised: 05/18/2022] [Accepted: 06/22/2022] [Indexed: 11/25/2022]
Abstract
BACKGROUND There is growing evidence that long non-coding RNAs (lncRNAs) play important roles in the progression of hepatocellular carcinoma (HCC) and may serve as diagnostic markers. This study investigates the diagnostic efficiency of the long intergenic non-protein-coding RNA 1793 (LINC01793) in hepatitis B virus (HBV)-related HCC. METHODS Bioinformatics methods were used to screen the aberrantly expressed lncRNAs in HCC tissues based on The Cancer Genome Atlas (TCGA). Quantitative reverse transcription polymerase chain reaction was performed to assess the expression of the candidate lncRNAs in tissues, cells and whole blood samples of patients with HBV-related HCC, liver cirrhosis (LC), chronic hepatitis (CHB), and healthy controls. Then, the correlations between LINC01793 and clinical characteristics were analyzed. Finally，the diagnostic value of LINC01793 was explored based on the receiver operating characteristic curve. RESULTS LINC01793 was remarkably upregulated in the HCC tissues and cells. It was highly expressed in the whole blood of the HBV-related HCC patients, unlike in that of the healthy controls and of the CHB and LC patients. Subsequent analysis revealed that high LINC01793 was related to the Barcelona Clinic Liver Cancer (P = 0.007), tumor invasion (P = 0.042), the number of tumors (P = 0.031) and serum level of alanine aminotransferase(p = 0.022). The areas under the curve of LINC01793, for distinguishing HCC from healthy controls, CHB and LC patients, were 0.824, 0.767 and 0.756, respectively. In addition, the combination of LINC01793 with alpha fetoprotein (AFP) had a stronger diagnostic value than LINC01793 or AFP alone in AFP-negative HCC patients. CONCLUSION High expression of LINC01793 is correlated with adverse clinical characteristics and can serve as a non-invasive biomarker of HCC.
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Affiliation(s)
- Cuiju Mo
- Department of Laboratory Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, China
| | - Junrong Wu
- Department of Laboratory Medicine, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi, China
| | - Jingzhe Sui
- Department of Laboratory Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, China
| | - Yan Deng
- Department of Laboratory Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, China
| | - Meng Li
- Department of Laboratory Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, China
| | - Zhao Cao
- Department of Laboratory Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, China
| | - Zuojian Hu
- Department of Laboratory Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, China
| | - Junhui Huang
- Department of Laboratory Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, China
| | - Shan Li
- Department of Laboratory Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, China.
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Stefanini B, Tonnini M, Serio I, Renzulli M, Tovoli F. Surveillance for hepatocellular carcinoma: current status and future perspectives for improvement. Expert Rev Anticancer Ther 2022; 22:371-381. [PMID: 35263211 DOI: 10.1080/14737140.2022.2052276] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Accepted: 03/08/2022] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Hepatocellular carcinoma (HCC) is a globally relevant medical problem. Fortunately, risk factors for this tumor have been identified, and surveillance protocols developed. Patients with liver cirrhosis have the highest risk of developing HCC and have historically been included in surveillance programs. Special categories have also emerged in recent years, especially patients with eradicated HCV infection or nonalcoholic fatty liver disease. Novel serum biomarkers and magnetic resonance imaging protocols are currently being proposed to refine existing surveillance protocols. AREAS COVERED We discuss the rationale of surveillance programs for HCC and report the most recent recommendations from international guidelines about this topic. Gray areas, such as nonalcoholic fatty liver disease and the role of intrahepatic cholangiocellular carcinoma, are also discussed. EXPERT OPINION Surveillance is recognized as a tool to favor early diagnosis of HCC, access to curative treatment, and increase survival, even if the supporting evidence is mainly based on observational studies. As new randomized clinical trials are difficult to propose, future challenges will include optimizing implementation in the primary care setting and a more personalized approach, balancing the opportunities and risks of overdiagnosis of novel techniques and biomarkers.
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Affiliation(s)
- Bernardo Stefanini
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Matteo Tonnini
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Ilaria Serio
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy
| | - Matteo Renzulli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy
| | - Francesco Tovoli
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
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Gil-Gómez A, Rojas Á, Liu CH, Gallego-Duran R, Muñoz-Hernandez R, Fassina G, Pontisso P, Ampuero J, Romero-Gómez M. Combination of squamous cell carcinoma antigen immunocomplex and alpha-fetoprotein in mid- and long-term prediction of hepatocellular carcinoma among cirrhotic patients. World J Gastroenterol 2021; 27:8343-8356. [PMID: 35068873 PMCID: PMC8717022 DOI: 10.3748/wjg.v27.i48.8343] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 06/27/2021] [Accepted: 12/10/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The combination of alpha-fetoprotein (AFP) and squamous cell carcinoma antigen immunocomplex (SCCA-IgM) have been proposed for its use in the screening of hepatocellular carcinoma (HCC). Current screening programs for all cirrhotic patients are controversial and a personalized screening is an unmet need in the precision medicine era.
AIM To determine the role of the combination of SCCA-IgM and AFP in predicting mid- and long-term appearance of HCC.
METHODS Two-hundred and three cirrhotic patients (Child A 74.9%, B 21.2%, C 3.9%) were followed-up prospectively every six months to screen HCC by ultrasound and AFP according to European Association for the Study of the Liver guidelines. The estimation cohort was recruited in Italy (30.5%; 62/203) and validation cohort from Spain (69.5%; 141/203). Patients underwent to evaluate SCCA-IgM by enzyme-linked immunosorbent assay (Hepa-IC, Xeptagen, Italy) and AFP levels at baseline. Patients were followed-up for 60 mo, being censored at the time of the appearance of HCC.
RESULTS There were 10.8% and 23.1% of HCC development at two- and five-years follow-up. Patients with HCC showed higher levels of SCCA-IgM than those without it (425.72 ± 568.33 AU/mL vs 195.93 ± 188.40 AU/mL, P = 0.009) during the five-year follow-up. In multivariate analysis, after adjusting by age, sex, aspartate transaminase and Child-Pugh, the following factors were independently associated with HCC: SCCA-IgM [Hazard ratio (HR) = 1.001, 95%CI: 1.000-1.002; P = 0.003], AFP (HR = 1.028, 95%CI: 1.009-1.046; P = 0.003) and creatinine (HR = 1.564 95%CI: 1.151-2.124; P = 0.004). The log-rank test of the combination resulted in 7.488 (P = 0.024) in estimation cohort and 11.061 (P = 0.004) in the validation cohort, and a 100% of correctly classified rate identifying a low-risk group in both cohorts in the two-year follow-up.
CONCLUSION We have constructed a predictive model based on the combination of SCCA-IgM and AFP that provides a new HCC screening method, which could be followed by tailored HCC surveillance for individual patients, especially for those cirrhotic patients belonging to the subgroup identified as low-risk of HCC development.
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Affiliation(s)
- Antonio Gil-Gómez
- SeLiver Group, Institute of Biomedicine of Seville, Seville 41013, Spain
- CIBERehd, Instituto de Salud Carlos III, Madrid 28029, Spain
- Mucosal Immunity Lab, IRCCS Humanitas Research Hospital, Milan 20089, Italy
| | - Ángela Rojas
- SeLiver Group, Institute of Biomedicine of Seville, Seville 41013, Spain
- CIBERehd, Instituto de Salud Carlos III, Madrid 28029, Spain
| | - Chang-Hai Liu
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610017, Sichuan Province, China
- State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital, Chengdu 610017, Sichuan Province, China
| | - Rocio Gallego-Duran
- SeLiver Group, Institute of Biomedicine of Seville, Seville 41013, Spain
- CIBERehd, Instituto de Salud Carlos III, Madrid 28029, Spain
| | - Rocio Muñoz-Hernandez
- SeLiver Group, Institute of Biomedicine of Seville, Seville 41013, Spain
- CIBERehd, Instituto de Salud Carlos III, Madrid 28029, Spain
| | | | - Patrizia Pontisso
- Department of Clinical and Experimental Medicine, University of Padova, Padova 35123, Italy
| | - Javier Ampuero
- SeLiver Group, Institute of Biomedicine of Seville, Seville 41013, Spain
- CIBERehd, Instituto de Salud Carlos III, Madrid 28029, Spain
- UCM Digestive Diseases, Virgen del Rocío University Hospital, Seville 41014, Spain
| | - Manuel Romero-Gómez
- SeLiver Group, Institute of Biomedicine of Seville, Seville 41013, Spain
- CIBERehd, Instituto de Salud Carlos III, Madrid 28029, Spain
- UCM Digestive Diseases, Virgen del Rocío University Hospital, Seville 41014, Spain
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Isfordink CJ, Maan R, de Man RA, van Erpecum KJ, van der Meer AJ. Should we continue surveillance for hepatocellular carcinoma and gastroesophageal varices in patients with cirrhosis and cured HCV infection? Eur J Intern Med 2021; 94:6-14. [PMID: 34563447 DOI: 10.1016/j.ejim.2021.08.023] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 08/02/2021] [Accepted: 08/27/2021] [Indexed: 12/13/2022]
Abstract
Hepatocellular carcinoma (HCC) and variceal bleeding are among the most common causes of liver-related mortality in patients with hepatitis C virus (HCV)-induced cirrhosis. Current guidelines recommend HCC and gastroesophageal varices (GEV) surveillance in patients with HCV infection and cirrhosis. However, since the recent introduction of direct-acting antivirals, most patients with cirrhosis are now cured of their chronic HCV infection. As virological cure is considered to substantially reduce the risk of cirrhosis-related complications, this review discusses the current literature concerning the surveillance of HCC and GEV in patients with HCV-induced cirrhosis with a focus on the setting following sustained virological response.
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Affiliation(s)
- Cas J Isfordink
- Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, the Netherlands; Division of Infectious Diseases, Amsterdam Infection & Immunity Institute Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - Raoel Maan
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Robert A de Man
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Karel J van Erpecum
- Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, the Netherlands
| | - Adriaan J van der Meer
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands.
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Carrier P, Guyot A, Debette‐Gratien M, Fredon F, Teissier M, Labrousse F, Loustaud‐Ratti V. Alpha‐fetoprotein and focal nodular hyperplasia: An unconventional couple. JGH Open 2021; 5:1316-1318. [PMID: 34816019 PMCID: PMC8593769 DOI: 10.1002/jgh3.12669] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 09/28/2021] [Accepted: 10/10/2021] [Indexed: 11/11/2022]
Abstract
We report the case of a 36‐year‐old patient who was initially managed for gynecomastia. The first biological analyses showed a moderately elevated alpha‐fetoprotein (AFP) level. After an endocrine etiology was excluded, an abdominal computed tomography scan showed typical focal nodular hyperplasia (FNH) proven by biopsy and showing expression of AFP in FNH cells. After follow‐up for 24 months, the serum AFP and liver radiology remained unchanged. The association between an elevated AFP and FNH is rarely described in the medical literature.
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Affiliation(s)
- Paul Carrier
- Hepatology and Gastroenterology Unit Limoges Dupuytren Hospital Limoges France
| | - Anne Guyot
- Pathology Department Limoges Dupuytren Hospital Limoges France
| | - Marilyne Debette‐Gratien
- Hepatology and Gastroenterology Unit Limoges Dupuytren Hospital Limoges France
- INSERM U‐1248 Limoges Faculty of Pharmacy Limoges France
| | - Fabien Fredon
- Digestive Surgery Department Limoges Dupuytren Hospital Limoges France
| | | | | | - Véronique Loustaud‐Ratti
- Hepatology and Gastroenterology Unit Limoges Dupuytren Hospital Limoges France
- INSERM U‐1248 Limoges Faculty of Pharmacy Limoges France
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Hernandez-Meza G, Vietti Violi N, Said D, Novogrodsky E, Villavisanis D, Maron SZ, Frere J, Schiano TD, Friedman S, Boffetta P, Branch A, Taouli B. MRI is the most commonly used imaging modality for HCC screening at a tertiary care transplant center. Abdom Radiol (NY) 2021; 46:5142-5151. [PMID: 34283266 DOI: 10.1007/s00261-021-03212-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Revised: 05/25/2021] [Accepted: 07/08/2021] [Indexed: 12/18/2022]
Abstract
PURPOSE In this study, we describe the patterns of hepatocellular carcinoma (HCC) screening with imaging and factors associated with imaging modality selection in a tertiary care transplant center. METHODS This was a retrospective study where all adult patients with cirrhosis and/or chronic hepatitis B virus infection referred for HCC screening with ultrasound (US), CT or MRI were identified during 2017. The association between imaging methods, demographic/clinical data were analyzed by uni- and multivariate analysis. RESULTS A total of 1437 patients were included (median age 61y, 59% male, median BMI 27.5 kg/m2, median AFP 3.4 ng/mL, 37% with HCV and 87% with cirrhosis). Index screening imaging method utilization included MRI (51%), US (33%) and CT (16%). Use of US as the index imaging modality for screening was significantly associated with race/ethnicity [Odds Ratio (OR) 1.71-2.01, all p < 0.05] in multivariate analysis. Presence of cirrhosis (OR 0.29, p < 0.001) and referral by a hepatologist (OR 0.23, p < 0.001) were associated with screening with MRI in the multivariate analysis; while gender, age, BMI, etiology and income at ZIP code of residence were not significantly associated with imaging modality selection. HCC was observed in 62 patients (prevalence 4.3%). Rate of HCC detection was significantly higher with MRI vs US (5.9% vs. 1.5%, p = 0.001). CONCLUSION MRI was the most frequently used modality (> 50%) for HCC screening in our tertiary care center, in contrast with the current practice guidelines. Race/ethnicity, cirrhosis and referral by a hepatologist were associated with the imaging method used for HCC screening.
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Affiliation(s)
- Gabriela Hernandez-Meza
- Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai (ISMMS), 1470 Madison Avenue, New York, NY, 10029, USA
- BioMedical Engineering and Imaging Institute, ISMMS, 1470 Madison Avenue, New York, NY, 10029, USA
| | - Naik Vietti Violi
- BioMedical Engineering and Imaging Institute, ISMMS, 1470 Madison Avenue, New York, NY, 10029, USA
- Department of Radiology, Lausanne University Hospital, Lausanne, Switzerland
| | - Daniela Said
- BioMedical Engineering and Imaging Institute, ISMMS, 1470 Madison Avenue, New York, NY, 10029, USA
- Department of Radiology, Universidad de los Andes, Santiago, Chile
| | - Eitan Novogrodsky
- Department of Radiology, Albert Einstein College of Medicine, New York, NY, USA
| | - Dillan Villavisanis
- Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai (ISMMS), 1470 Madison Avenue, New York, NY, 10029, USA
- BioMedical Engineering and Imaging Institute, ISMMS, 1470 Madison Avenue, New York, NY, 10029, USA
| | - Samuel Z Maron
- Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai (ISMMS), 1470 Madison Avenue, New York, NY, 10029, USA
- BioMedical Engineering and Imaging Institute, ISMMS, 1470 Madison Avenue, New York, NY, 10029, USA
| | - Justin Frere
- Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai (ISMMS), 1470 Madison Avenue, New York, NY, 10029, USA
- BioMedical Engineering and Imaging Institute, ISMMS, 1470 Madison Avenue, New York, NY, 10029, USA
| | - Thomas D Schiano
- Recanati/Miller Transplantation Institute, ISMMS, New York, NY, USA
| | | | - Paolo Boffetta
- Tisch Cancer Institute, ISMMS, New York, NY, USA
- Department of Family, Population & Preventive Medicine, Renaissance School of Medicine, Stony Brook, NY, USA
| | - Andrea Branch
- Division of Liver Diseases, ISMMS, New York, NY, USA
| | - Bachir Taouli
- Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai (ISMMS), 1470 Madison Avenue, New York, NY, 10029, USA.
- BioMedical Engineering and Imaging Institute, ISMMS, 1470 Madison Avenue, New York, NY, 10029, USA.
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Singal AG, Patibandla S, Obi J, Fullington H, Parikh ND, Yopp AC, Marrero JA. Benefits and Harms of Hepatocellular Carcinoma Surveillance in a Prospective Cohort of Patients With Cirrhosis. Clin Gastroenterol Hepatol 2021; 19:1925-1932.e1. [PMID: 32920214 PMCID: PMC7943645 DOI: 10.1016/j.cgh.2020.09.014] [Citation(s) in RCA: 60] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 08/27/2020] [Accepted: 09/04/2020] [Indexed: 12/19/2022]
Abstract
BACKGROUND & AIMS The value of a cancer screening programs is defined by its balance of benefits and harms; however, there are few data evaluating both attributes for hepatocellular carcinoma (HCC) surveillance. We aimed to characterize benefits and harms of HCC surveillance in a large prospective cohort of patients with cirrhosis. METHODS We conducted a secondary analysis of a clinical trial evaluating HCC surveillance among patients with cirrhosis at a safety-net health system enrolled between December 2014 and July 2015. We quantified surveillance-related benefits, defined as early HCC detection and curative treatment receipt, and physical harms, defined as diagnostic procedures for false positive or indeterminate results, over an 18-month period. RESULTS Of 614 cirrhosis patients with ≥1 surveillance exam, abnormal results were observed in 118 (19.2%) patients. Twenty-six patients developed HCC during follow-up, of whom 16 (61.5%) were detected by surveillance. The proportion of HCC detected at BCLC stage 0/A (62.5% vs 50%, p = .69) and who underwent curative treatment (43.8% vs. 40.0%, p = 1.0) did not significantly differ between surveillance-detected patients and those diagnosed incidentally/symptomatically. Physical harms were observed in 54 (8.8%) patients who underwent surveillance - most of mild severity with only 1 diagnostic CT or MRI and none undergoing invasive testing such as biopsy. Incidental findings on follow-up imaging were found in 40 (6.5%) patients -23 of low clinical importance and 17 medium clinical importance. CONCLUSIONS In our cohort of patients with cirrhosis, HCC surveillance was associated with high early tumor detection and minimal physical harms.
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Affiliation(s)
- Amit G. Singal
- Department of Internal Medicine, UT Southwestern Medical Center and Parkland Health Hospital System, Dallas, TX,Department of Population Sciences, UT Southwestern Medical Center, Dallas, TX,Harold C. Simmons Cancer Center, UT Southwestern Medical Center, Dallas, TX
| | - Sruthi Patibandla
- Department of Internal Medicine, UT Southwestern Medical Center and Parkland Health Hospital System, Dallas, TX
| | - Joseph Obi
- Department of Internal Medicine, UT Southwestern Medical Center and Parkland Health Hospital System, Dallas, TX
| | - Hannah Fullington
- Department of Population Sciences, UT Southwestern Medical Center, Dallas, TX
| | - Neehar D. Parikh
- Department of Internal Medicine, University of Michigan, Ann Arbor MI
| | - Adam C. Yopp
- Harold C. Simmons Cancer Center, UT Southwestern Medical Center, Dallas, TX,Department of Surgery, UT Southwestern Medical Center, Dallas, TX
| | - Jorge A. Marrero
- Department of Internal Medicine, UT Southwestern Medical Center and Parkland Health Hospital System, Dallas, TX,Harold C. Simmons Cancer Center, UT Southwestern Medical Center, Dallas, TX
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Delaney LJ, Tantawi M, Wessner CE, Machado P, Forsberg F, Lyshchik A, O'Kane P, Liu JB, Civan J, Tan A, Anton K, Shaw CM, Eisenbrey JR. Predicting Long-Term Hepatocellular Carcinoma Response to Transarterial Radioembolization Using Contrast-Enhanced Ultrasound: Initial Experiences. ULTRASOUND IN MEDICINE & BIOLOGY 2021; 47:2523-2531. [PMID: 34130880 PMCID: PMC8355136 DOI: 10.1016/j.ultrasmedbio.2021.05.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 02/26/2021] [Accepted: 05/06/2021] [Indexed: 05/12/2023]
Abstract
Conventional cross-sectional imaging done shortly after radioembolization of hepatocellular carcinoma (HCC) does not reliably predict long-term response to treatment. This study evaluated whether quantitative contrast-enhanced ultrasound (CEUS) can predict the long-term response of HCC to yttrium-90 (Y-90) treatment. Fifteen patients underwent CEUS at three time points: immediately following treatment and 1 and 2 wk post-treatment. Response 3-6 mo after treatment was categorized on contrast-enhanced magnetic resonance imaging by two experienced radiologists using the Modified Response Evaluation Criteria in Solid Tumors. CEUS data were analyzed by quantifying tumor perfusion and residual fractional vascularity using time-intensity curves. Patients with stable disease on magnetic resonance imaging had significantly greater fractional vascularity 2 wk post-treatment (65.15%) than those with partial or complete response (13.8 ± 9.9%, p = 0.007, and 14.9 ± 15.4%, p = 0.009, respectively). Complete responders had lower tumor vascularity at 2 wk than at post-operative examination (-38.3 ± 15.4%, p = 0.045). Thus, this pilot study suggests CEUS may provide an earlier indication of Y-90 treatment response than cross-sectional imaging.
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Affiliation(s)
- Lauren J Delaney
- Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Mohamed Tantawi
- Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Corinne E Wessner
- Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Priscilla Machado
- Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Flemming Forsberg
- Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Andrej Lyshchik
- Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Patrick O'Kane
- Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Ji-Bin Liu
- Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Jesse Civan
- Division of Gastroenterology and Hepatology, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Allison Tan
- Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Kevin Anton
- Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Colette M Shaw
- Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - John R Eisenbrey
- Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
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Sachar Y, Brahmania M, Dhanasekaran R, Congly SE. Screening for Hepatocellular Carcinoma in Patients with Hepatitis B. Viruses 2021; 13:1318. [PMID: 34372524 PMCID: PMC8310362 DOI: 10.3390/v13071318] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 07/05/2021] [Accepted: 07/05/2021] [Indexed: 12/18/2022] Open
Abstract
Chronic hepatitis B (CHB) infection is a significant risk factor for developing hepatocellular carcinoma (HCC). As HCC is associated with significant morbidity and mortality, screening patients with CHB at a high risk for HCC is recommended in an attempt to improve these outcomes. However, the screening recommendations on who to screen and how often are not uniform. Identifying patients at the highest risk of HCC would allow for the best use of health resources. In this review, we evaluate the literature on screening patients with CHB for HCC, strategies for optimizing adherence to screening, and potential risk stratification tools to identify patients with CHB at a high risk of developing HCC.
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Affiliation(s)
- Yashasavi Sachar
- London Health Sciences Center, Department of Medicine, Division of Gastroenterology, Western University, London, ON N6A 5A5, Canada; (Y.S.); (M.B.)
| | - Mayur Brahmania
- London Health Sciences Center, Department of Medicine, Division of Gastroenterology, Western University, London, ON N6A 5A5, Canada; (Y.S.); (M.B.)
- Centre for Quality, Innovation and Safety, Schulich School of Medicine & Dentistry, Western University, London, ON N6A 5W9, Canada
| | - Renumathy Dhanasekaran
- Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University, Stanford, CA 94305, USA;
| | - Stephen E. Congly
- Department of Medicine, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4Z6, Canada
- O’Brien Institute of Public Health, University of Calgary, Calgary, AB T2N 4Z6, Canada
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Tayob N, Corley DA, Christie I, Almers L, Rahal AK, Richardson P, White DL, Davila J, Kanwal F, El-Serag HB. Validation of the Updated Hepatocellular Carcinoma Early Detection Screening Algorithm in a Community-Based Cohort of Patients With Cirrhosis of Multiple Etiologies. Clin Gastroenterol Hepatol 2021; 19:1443-1450.e6. [PMID: 32768590 PMCID: PMC8201947 DOI: 10.1016/j.cgh.2020.07.065] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Revised: 07/28/2020] [Accepted: 07/31/2020] [Indexed: 01/07/2023]
Abstract
BACKGROUND & AIMS The Hepatocellular carcinoma (HCC) Early detection Screening (HES) algorithm has been proposed to improve the performance of the serum alpha-fetoprotein (AFP) test in surveillance for HCC. The HES algorithm incorporates data on age, level of alanine aminotransferase, platelet count, and rate of AFP change to increase likelihood of earlier detection and thereby reduce HCC-related mortality. We updated the HES algorithm to include etiology of cirrhosis and validated it in a community-based cohort. METHODS We collected data from the Veterans Health Administration, from 2010 through 2015, on etiologies for HCC, including hepatitis C, hepatitis B, alcoholic liver disease, and non-alcoholic fatty liver disease. We used these data to update the HES algorithm and tested its accuracy using data from patients with cirrhosis in the Kaiser Permanente Northern California healthcare system (validation cohort). RESULTS Among the 7432 patients with cirrhosis in the validation cohort, 1102 were diagnosed with HCC during a median follow-up time of 3.21 years; 709 patients had early-stage HCC. The HES algorithm identified patients who would receive a diagnosis of early-stage HCC within the next 6 months with 51.20% sensitivity and 90.00% specificity, compared with 46.02% sensitivity for the AFP test alone (5.18% absolute improvement; P = .0015). In HCC screening, a positive result from HES or AFP test leads to follow-up evaluation with more sensitive imaging methods. The number of early-stage HCC cases detected per 1000 imaging analyses were 136.46 with the HES algorithm vs 118.01 with the AFP test alone (P < .0005). The HES algorithm identified 56.00% of patients with HCC in the 6 months before their diagnosis despite no detection of nodules by surveillance ultrasound; the AFP test identified only 50.00% of these patients. CONCLUSIONS We validated the HES algorithm using data from a diverse community-based cohort of patients with cirrhosis. The algorithm offers a modest but useful advantage over the AFP test alone in detection of early-stage HCC with virtually no added cost.
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Affiliation(s)
- Nabihah Tayob
- Department of Data Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts; Department of Medicine, Harvard Medical School, Boston, Massachusetts
| | - Douglas A. Corley
- Kaiser Permanente, Northern California, San Francisco Medical Center, San Francisco, California; Division of Research, Oakland, California
| | - Israel Christie
- Houston VA Health Services Research and Development Service Center of Excellence, Houston, Texas; Section of Health Services Research, Michael E. DeBakey VA Medical Center, Houston, Texas; Department of Medicine, Baylor College of Medicine, Houston, Texas
| | - Lucy Almers
- Kaiser Permanente, Northern California, San Francisco Medical Center, San Francisco, California; Division of Research, Oakland, California
| | - Ahmed K Rahal
- Department of Medicine, Baylor College of Medicine, Houston, Texas
| | - Peter Richardson
- Houston VA Health Services Research and Development Service Center of Excellence, Houston, Texas; Section of Health Services Research, Michael E. DeBakey VA Medical Center, Houston, Texas; Department of Medicine, Baylor College of Medicine, Houston, Texas
| | - Donna L. White
- Houston VA Health Services Research and Development Service Center of Excellence, Houston, Texas; Section of Health Services Research, Michael E. DeBakey VA Medical Center, Houston, Texas; Department of Medicine, Baylor College of Medicine, Houston, Texas
| | - Jessica Davila
- Houston VA Health Services Research and Development Service Center of Excellence, Houston, Texas; Section of Health Services Research, Michael E. DeBakey VA Medical Center, Houston, Texas; Department of Medicine, Baylor College of Medicine, Houston, Texas
| | - Fasiha Kanwal
- Houston VA Health Services Research and Development Service Center of Excellence, Houston, Texas; Section of Health Services Research, Michael E. DeBakey VA Medical Center, Houston, Texas; Department of Medicine, Baylor College of Medicine, Houston, Texas
| | - Hashem B El-Serag
- Houston VA Health Services Research and Development Service Center of Excellence, Houston, Texas; Section of Health Services Research, Michael E. DeBakey VA Medical Center, Houston, Texas; Department of Medicine, Baylor College of Medicine, Houston, Texas.
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Wang J, Huang R, Huang Y, Chen Y, Chen F. Overexpression of NOP58 as a Prognostic Marker in Hepatocellular Carcinoma: A TCGA Data-Based Analysis. Adv Ther 2021; 38:3342-3361. [PMID: 34014550 DOI: 10.1007/s12325-021-01762-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 04/27/2021] [Indexed: 12/24/2022]
Abstract
INTRODUCTION NOP58 ribonucleoprotein, a core component of box C/D small nucleolar ribonucleoproteins, is involved in various cell physiological processes. However, its role in hepatocellular carcinoma (HCC) remains very unclear. We aim to investigate NOP58 expression and its probable prognostic value in patients with HCC based on The Cancer Genome Atlas (TCGA) database. METHODS RNA sequencing data and clinicopathological characteristics of patients with HCC were collected from TCGA database. Expression of NOP58 in HCC tissues and normal tissues was analyzed by Wilcoxon rank-sum test. Patients were divided into high and low subgroups according to median expression of NOP58. Logistic regression, gene set enrichment analysis (GSEA), and single-sample gene set enrichment analysis (ssGSEA) were conducted to annotate biological function and immune infiltration of NOP58. RESULTS NOP58 was significantly overexpressed in HCC tissues and correlated with significantly high tumor stage [odds ratio (OR) 10.01, 95% confidence interval (CI) 10.01-10.03; P = 0.003], advanced pathologic stage (OR 10.02, 95% CI 10.01-10.03; P < 0.001), advanced histologic stage (OR 10.03, 95% CI 10.02-10.04; P < 0.001), vascular invasion (OR 10.02, 95% CI 10.01-10.03; P = 0.003), poor performance status (OR 10.01, 95% CI 10.01-10.03; P = 0.003), and Mut-TP53 status (OR 10.02, 95% CI 10.01-10.03; P < 0.001). Elevated NOP58 expression had poor disease-specific survival (DSS; P < 0.001), progression-free interval (P = 0.006), and overall survival (OS; P < 0.001). NOP58 expression was independently correlated with OS (HR 1.731, 95% CI 10.037-2.890; P = 0.036). GSEA demonstrated that various cell cycle pathways along with RB-1 pathway, interleukin-10 signaling, regulation of TP53 activity, and P53 downstream pathway were differentially enriched in NOP58 high expression phenotype. NOP58 expression was positively correlated with infiltrating the levels of T helper type 2 (Th2) cells. CONCLUSIONS Overexpression of NOP58 is negatively correlated with overall survival in patients with HCC and might be a potential biomarker for prognosis of HCC.
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Kuo SC, Lin CN, Lin YJ, Chen WY, Hwang JS, Wang JD. Optimal Intervals of Ultrasonography Screening for Early Diagnosis of Hepatocellular Carcinoma in Taiwan. JAMA Netw Open 2021; 4:e2114680. [PMID: 34165580 PMCID: PMC8226422 DOI: 10.1001/jamanetworkopen.2021.14680] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
IMPORTANCE There are different clinical practices regarding ultrasonography screening intervals for hepatocellular carcinoma (HCC) despite recommendations from international guidelines. OBJECTIVE To evaluate whether ultrasonography screening using intervals suggested by international guidelines is associated with cancer stage shifting, reductions in mortality, and improved quality of life (QoL) for patients with HCC. DESIGN, SETTING, AND PARTICIPANTS This nationwide comparative effectiveness research study estimated lifetime survival functions using interlinkages of 3 databases from Taiwan-the Taiwan National Health Insurance, Taiwan National Cancer Registry, and National Mortality Registry-combined with QoL measurements obtained from National Cheng Kung University Hospital. In total, 114 022 patients listed as having newly diagnosed HCC from 2002 through 2015 in the Taiwan National Cancer Registry were followed up until 2017. The QoL values of 1059 patients with HCC who visited National Cheng Kung University Hospital were prospectively measured with the European QoL-5 dimensions questionnaire from 2011 through 2019. Patients were categorized based on the time between their last ultrasonography screening and the index date (90 days prior to HCC diagnosis) as 1 of 5 subcohorts: 6 months (0-6 months), 12 months (7-12 months), 24 months (13-24 months), 36 months (25-36 months), and longer than 36 months (no screening in the previous 3 years). Data were analyzed from April 2020 to April 2021. MAIN OUTCOMES AND MEASURES Life expectancy, quality-adjusted life expectancy, and loss of life expectancy or loss of quality-adjusted life expectancy compared with age-, sex-, and calendar year-matched cohorts. RESULTS There were 59 194 patients with Barcelona Clinic Liver Cancer staging information, including 42 081 men (mean [SD] age, 62.2 [12.6] years) and 17 113 women (mean [SD] age, 69.0 [11.2] years). There was a consistent trend showing that the longer the interval between ultrasonography examinations, the higher the loss of life expectancy and loss of quality-adjusted life expectancy for both sexes. Loss of quality-adjusted life expectancy values for male subcohorts were 10.0 (95% CI, 9.1-10.9) quality-adjusted life-years (QALYs) for ultrasonography screening intervals of 6 months, 11.1 (95% CI, 10.4-11.8) QALYs for 12 months, 12.1 (95% CI, 11.5-12.7) QALYs for 24 months, 13.1 (95% CI, 12.6-13.6) QALYs for 36 months, and 14.6 (95% CI, 14.2-15.0) QALYs for longer than 36 months. Loss of quality-adjusted life expectancy values for female subcohorts were 9.0 (95% CI, 8.3-9.6) QALYs for 6 months, 9.7 (95% CI, 9.2-10.2) QALYs for 12 months, 10.3 (95% CI, 9.8-10.7) QALYs for 24 months, 10.7 (95% CI, 10.2-11.1) QALYs for 36 months, and 11.4 (95% CI, 11.0-11.8) QALYs for longer than 36 months. Patients with underlying hepatitis B virus infection or cirrhosis had the greatest improvement in life expectancy with shorter screening intervals. CONCLUSIONS AND RELEVANCE Regular ultrasonography screening with intervals less than 6 to 12 months may be associated with early detection of HCC, save lives, and improve the quality of life for patients with HCC from a lifetime perspective.
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Affiliation(s)
- Shih-Chiang Kuo
- Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chia-Ni Lin
- Department of Public Health, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yih-Jyh Lin
- Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Wei-Ying Chen
- Department of Public Health, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | | | - Jung-Der Wang
- Department of Public Health, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Department of Occupational and Environmental Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
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We need stronger evidence for (or against) hepatocellular carcinoma surveillance. J Hepatol 2021; 74:1234-1239. [PMID: 33465402 DOI: 10.1016/j.jhep.2020.12.029] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Revised: 12/22/2020] [Accepted: 12/23/2020] [Indexed: 02/07/2023]
Abstract
Current guidelines from EASL recommend that most patients with cirrhosis are offered surveillance for hepatocellular carcinoma (HCC), but fewer patients than expected actually receive it. The recommendation is based on observational studies and simulations, not randomised trials. In this opinion piece we argue that a randomised trial of HCC surveillance vs. no surveillance is necessary and feasible, and we believe that clinician and patient participation in HCC surveillance would be better if it were based on trial results demonstrating its value.
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Su F, Weiss NS, Beste LA, Moon AM, Jin GY, Green P, Berry K, Ioannou GN. Screening is associated with a lower risk of hepatocellular carcinoma-related mortality in patients with chronic hepatitis B. J Hepatol 2021; 74:850-859. [PMID: 33245934 PMCID: PMC8045451 DOI: 10.1016/j.jhep.2020.11.023] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2020] [Revised: 11/06/2020] [Accepted: 11/16/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS Patients with chronic hepatitis B (CHB) infection routinely undergo screening for hepatocellular carcinoma (HCC), but the efficacy of screening remains unclear. We aimed to evaluate the impact of screening with ultrasound and/or serum alpha-fetoprotein (AFP) on HCC-related mortality in patients with CHB. METHODS We performed a matched case-control study of patients with CHB receiving care through the Veterans Affairs (VA) health administration. Cases were patients who died of HCC between 01/01/2004 and 12/31/2017, while controls were patients with CHB who did not die of HCC. Cases were matched to controls by CHB diagnosis date, age, sex, race/ethnicity, cirrhosis, antiviral therapy exposure, hepatitis B e antigen status, and viral load. We identified screening ultrasound and AFPs obtained in the 4 years preceding HCC diagnosis in cases and the equivalent index date in controls. Using conditional logistic regression, we compared cases and controls with respect to receipt of screening. A lower likelihood of screening in cases corresponds to an association between screening and reduced risk of HCC-related mortality. RESULTS We identified 169 cases, matched to 169 controls. Fewer cases than controls underwent screening with either screening modality (33.7% vs. 58.6%) or both modalities (19.5% vs. 34.4%). In multivariable conditional logistic regression, screening with either modality was associated with a lower risk of HCC-related mortality (adjusted odds ratio [aOR] 0.21, 95% CI 0.09-0.50), as was screening with both modalities (aOR of 0.13; 95% CI 0.04-0.43). CONCLUSIONS HCC screening was associated with a substantial reduction in HCC-related mortality in VA patients with CHB. LAY SUMMARY Patients with hepatitis B infection have a high risk of developing liver cancer. It is therefore recommended that they undergo frequent screening for liver cancer, but whether this leads to a lower risk of dying from liver cancer is not clear. In this study, we show that liver cancer screening is associated with a reduction in the mortality from liver cancer in patients with hepatitis B infection.
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Affiliation(s)
- Feng Su
- Divisions of Gastroenterology, Veterans Affairs Puget Sound Healthcare System and University of Washington, Seattle WA.,Department of Epidemiology, University of Washington, Seattle WA, and the Fred Hutchinson Cancer Research Center, Seattle WA
| | - Noel S. Weiss
- Department of Epidemiology, University of Washington, Seattle WA, and the Fred Hutchinson Cancer Research Center, Seattle WA
| | - Lauren A. Beste
- Division of General Internal Medicine, Veterans Affairs Puget Sound Healthcare System and University of Washington, Seattle WA
| | - Andrew M. Moon
- Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Ga-Young Jin
- Health Services Research and Development, Veterans Affairs Puget Sound Healthcare System, Seattle WA
| | - Pamela Green
- Health Services Research and Development, Veterans Affairs Puget Sound Healthcare System, Seattle WA
| | - Kristin Berry
- Health Services Research and Development, Veterans Affairs Puget Sound Healthcare System, Seattle WA
| | - George N. Ioannou
- Divisions of Gastroenterology, Veterans Affairs Puget Sound Healthcare System and University of Washington, Seattle WA
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Loosen SH, Castoldi M, Jördens MS, Roy S, Vucur M, Kandler J, Hammerich L, Mohr R, Tacke F, Ulmer TF, Neumann UP, Luedde T, Roderburg C. Serum levels of circulating microRNA-107 are elevated in patients with early-stage HCC. PLoS One 2021; 16:e0247917. [PMID: 33711036 PMCID: PMC7954311 DOI: 10.1371/journal.pone.0247917] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Accepted: 02/16/2021] [Indexed: 12/14/2022] Open
Abstract
Background Early detection of hepatocellular carcinoma (HCC), the most common primary liver malignancy, is crucial to offer patients a potentially curative treatment strategy such as surgical resection or liver transplantation (LT). However, easily accessible biomarkers facilitating an early diagnosis of HCC as well as a reliable risk prediction are currently missing. The microRNA(miR)-107 has recently been described as a driver of HCC in both murine and human HCC but data on circulating miR-107 in HCC patients are scarce. In the present study, we evaluated a potential diagnostic and/or prognostic role of circulating miR-107 in patients undergoing tumor resection or LT for early-stage HCC. Methods The Kmplot bioinformatic tool was used to query publicly available databases (including TCGA, GEO and EGA) in order to analyse the prognostic value of tumoral miR-107 expression in HCC patients (n = 372). Serum levels of miR-107 were measured by qPCR in n = 45 HCC patients undergoing surgical tumor resection (n = 37) or LT (n = 8) as well as n = 18 healthy control samples. Results were correlated with clinical data. Results A high tumoral expression of miR-107 was associated with a significantly better overall survival compared to patients with low miR-107 expression levels (HR 0.69, 95% CI 0.48–0.99, p = 0.041). In addition, serum levels of miR-107 were significantly higher in HCC patients when compared to healthy controls. However, miR-107 serum levels in HCC patients were independent of different disease etiology, tumor stage or tumor grading. HCC patients with baseline miR-107 expression levels above a calculated ideal prognostic cut-off value (9.82) showed a clear trend towards an impaired overall survival (p = 0.119). Conclusion Tumoral miR-107 expression levels are a potential prognostic marker in early stage HCC. Furthermore, we describe a potential role of circulating miR-107 levels as a diagnostic biomarker in patients with early-stage HCC.
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Affiliation(s)
- Sven H. Loosen
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Mirco Castoldi
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Markus S. Jördens
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Sanchary Roy
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Mihael Vucur
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Jennis Kandler
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Linda Hammerich
- Department of Hepatology and Gastroenterology, Charité University Medicine Berlin, Berlin, Germany
| | - Raphael Mohr
- Department of Hepatology and Gastroenterology, Charité University Medicine Berlin, Berlin, Germany
| | - Frank Tacke
- Department of Hepatology and Gastroenterology, Charité University Medicine Berlin, Berlin, Germany
| | - Tom F. Ulmer
- Department of Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Aachen, Germany
| | - Ulf P. Neumann
- Department of Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Aachen, Germany
| | - Tom Luedde
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- * E-mail: (TL); (CR)
| | - Christoph Roderburg
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Department of Hepatology and Gastroenterology, Charité University Medicine Berlin, Berlin, Germany
- * E-mail: (TL); (CR)
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Song JH, Goh MJ, Park Y, Oh JH, Kang W, Sinn DH, Gwak GY, Paik YH, Choi MS, Lee JH, Koh KC, Paik SW. Prognosis of hepatocellular carcinoma patients diagnosed under regular surveillance: potential implications for surveillance goal. Scand J Gastroenterol 2021; 56:274-280. [PMID: 33399022 DOI: 10.1080/00365521.2020.1866063] [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] [Indexed: 02/04/2023]
Abstract
AIMS The goal of hepatocellular carcinoma (HCC) surveillance is to diagnose cancer at an early stage when treatment is likely to provide the best outcome and thereby, reduce mortality. However, no specific criteria define the 'early stage' for tumors diagnosed under HCC surveillance. We aimed to analyze factors that determined the outcome of HCC patients diagnosed under regular surveillance, to find out how early it is necessary to detect tumors during surveillance. METHODS A retrospective cohort of 874 HCC patients with preserved liver function (Child-Pugh A) who were diagnosed under regular HCC surveillance at Samsung Medical Center from 2014 to 2016 and did not receive liver transplantation as an initial treatment were analyzed. The primary outcome was overall survival (OS). RESULTS Tumor size, presence of vascular invasion, albumin-bilirubin grade, and initial treatment modality were independent factors for OS in multivariable analysis. When categorized according to the tumor size, the risk of mortality increased for tumors of > 3 cm, while tumors of 2-3 cm showed similar mortality risks as tumors of ≤2 cm. When categorized according to the tumor factors, curative-intent treatment (resection or ablation) can be applied to 84.5% with excellent outcomes (5-year OS rate, 93.4%), for tumors of ≤3 cm without vascular invasion. CONCLUSIONS When tumors of ≤3 cm were detected and had no vascular invasion, curative-intent treatment was applied for most patients and showed excellent OS. This finding suggests that to detect tumors of <3 cm without vascular invasion may be considered as the goal of HCC surveillance.
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Affiliation(s)
- Joo Hye Song
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Myung Ji Goh
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Yewan Park
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Joo Hyun Oh
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Wonseok Kang
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Geum-Youn Gwak
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Yong-Han Paik
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Moon Seok Choi
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Joon Hyeok Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Kwang Cheol Koh
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Seung Woon Paik
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
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Identification of a Nine Immune-Related lncRNA Signature as a Novel Diagnostic Biomarker for Hepatocellular Carcinoma. BIOMED RESEARCH INTERNATIONAL 2021; 2021:9798231. [PMID: 33506049 PMCID: PMC7808810 DOI: 10.1155/2021/9798231] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 10/20/2020] [Accepted: 12/18/2020] [Indexed: 02/06/2023]
Abstract
Hepatocellular carcinoma (HCC) ranks fifth among common cancers and is the second most common cause of cancer-related mortality worldwide. This study is aimed at identifying an immune-related long noncoding RNA (lncRNA) signature as a potential biomarker with prognostic value to improve early diagnosis and provide potential therapeutic targets for HCC patients. The subjects of this study were HCC samples with complete transcriptome data and clinical information downloaded from The Cancer Genome Atlas (TCGA) database. We then extracted the immune-related mRNA and lncRNA expression profiles. Based on the expression profiles of immune-related lncRNAs, we identified a nine-lncRNA signature that was related to the progression of HCC. The risk score was calculated based on the expression level of the nine lncRNAs of each sample, which divided patients into high-risk and low-risk groups. We found that the increased risk score was associated with a poor prognosis of HCC patients. To assess the accuracy of the survival model, we calculated a receiver operating characteristic (ROC) for validation. The curve showed that the area under the curve (AUC) for the risk score was 0.792. Besides, both principal component analysis (PCA) and gene set enrichment analysis (GSEA) were further used for functional annotation. We found that the distribution patterns were different between the low-risk and high-risk groups in PCA, and the underlying mechanism by which the nine lncRNAs promoted the progression of HCC involved an abnormal immune status. Finally, we analyzed the infiltration of twenty-nine kinds of immune cells and the activation of immune function in HCC using the ssGSEA algorithm. The results showed that aDCs, iDCs, macrophages, Tfh, Th1, Treg, and NK cells were correlated with the progress of HCC patients. And the immune functions including APC costimulation, CCR, check point, HLA, MHC class I, and Type II IFN responses were also significantly different between the high-risk and low-risk groups. In conclusion, our study identified a nine-lncRNA signature with potential prognostic value for patients with HCC, which could be used as a new biomarker for the diagnosis and immunotherapy of HCC.
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Raffetti E, Portolani N, Molfino S, Mentasti S, Baiocchi GL, Magoni M, Donato F. Is survival for hepatocellular carcinoma increasing? A population-based study on survival of hepatocellular carcinoma patients in the 1990s and 2000s. Clin Res Hepatol Gastroenterol 2021; 45:101433. [PMID: 32409284 DOI: 10.1016/j.clinre.2020.04.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Revised: 04/06/2020] [Accepted: 04/11/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND Improvement of survival rates for hepatocellular carcinoma during the last two decades and related factors are still debated. This study aimed to evaluate the risk of death and the role of prognostic factors in patients with hepatocellular carcinoma diagnosed in 1995-2001 and 2004-2006. METHODS We performed univariate and multivariable survival analyses of subjects with a first hepatocellular carcinoma diagnosis in 1995-2001 and in 2004-2006, all residing in Brescia province, Italy. Mediation analysis of treatment role in survival was conducted. RESULTS During follow-up (median 21.1 months) 913 subjects died (95.5%). The 1-, 3- and 5-year survival rates were higher for cases diagnosed in 2004-2006 (64.4%, 35.9% and 24.3%) than in 1995-2001 (60.8%, 34.5% and 20.7%). T stage, metastasis, cirrhosis, Child-Pugh class, portal vein invasion, serum creatinine level, treatment approach and diabetes were survival predictors in both periods. Patients with diagnosis in 2004-2006 had 36% lower risk of death than those with diagnosis in 1995-2001 using adjusted Cox proportional hazard model. The association between diagnosis period and risk of death was mediated by changes in treatment approach. CONCLUSION We observed a decreased risk of death for first hepatocellular carcinoma diagnosis from 2004-2006 to 1995-2001, which was partially attributable to improvements in treatment approach.
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Affiliation(s)
- Elena Raffetti
- Department of Global Public Health, Karolinska Institutet, Solnavägen 1 E, 11365 Stockholm, Sweden.
| | - Nazario Portolani
- Surgical Clinic, Department of Clinical and Experimental Sciences, University of Brescia, Piazzale Spedali Civili 1, 25123 Brescia, Italy.
| | - Sarah Molfino
- Surgical Clinic, Department of Clinical and Experimental Sciences, University of Brescia, Piazzale Spedali Civili 1, 25123 Brescia, Italy.
| | - Sara Mentasti
- Unit of Hygiene, Epidemiology and Public Health, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Italy, Viale Europa 11, 25123 Brescia, Italy.
| | - Gian Luca Baiocchi
- Surgical Clinic, Department of Clinical and Experimental Sciences, University of Brescia, Piazzale Spedali Civili 1, 25123 Brescia, Italy.
| | - Michele Magoni
- Cancer Registry of Brescia Province, Unit of Epidemiology, Brescia Health Protection Agency, Viale Duca degli Abruzzi 15, 25124 Brescia, Italy.
| | - Francesco Donato
- Unit of Hygiene, Epidemiology and Public Health, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Italy, Viale Europa 11, 25123 Brescia, Italy.
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Does Hepatocellular Carcinoma Surveillance Increase Survival in At-Risk Populations? Patient Selection, Biomarkers, and Barriers. Dig Dis Sci 2020; 65:3456-3462. [PMID: 32860090 PMCID: PMC7669568 DOI: 10.1007/s10620-020-06550-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma (HCC) is a highly morbid and prevalent cancer globally. While high quality evidence for mortality benefit of HCC surveillance is lacking, early detection of HCC is likely beneficial as prognosis is highly correlated with tumor stage. High risk populations, including patients with cirrhosis and subgroups with Hepatitis B, should undergo surveillance with ultrasound ± alpha-fetoprotein (AFP) at 6-month intervals. In addition, emerging data suggest that patients with Hepatitis C cirrhosis who achieve sustained virologic response should continue surveillance. Further research is needed to determine the value of surveillance in patients with nonalcoholic fatty liver disease in the absence of cirrhosis or with advanced fibrosis of other etiologies. Newer biomarkers and models such as Lens culinaris agglutinin-reactive fraction of AFP, des-γ-carboxy prothrombin, and the GALAD score are increasingly utilized in the diagnosis and prognostication of HCC. The role of these biomarkers in surveillance is still under investigation but may potentially offer a more practical alternative to traditional image-based surveillance. Despite recommendations from multiple professional society guidelines, many at-risk patients do not receive HCC surveillance due to barriers at the patient, clinician, and health care system levels. Strategies such as implementing patient navigation services, educating clinicians about surveillance guidelines, and creating automated outreach systems, may improve surveillance rates and ultimately reduce morbidity and mortality from HCC.
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Singh G, Yoshida EM, Rathi S, Marquez V, Kim P, Erb SR, Salh BS. Biomarkers for hepatocellular cancer. World J Hepatol 2020; 12:558-573. [PMID: 33033565 PMCID: PMC7522562 DOI: 10.4254/wjh.v12.i9.558] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Revised: 07/06/2020] [Accepted: 08/25/2020] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. If diagnosed early, curative treatment options such as surgical resection, loco-regional therapies, and liver transplantation are available to patients, increasing their chances of survival and improving their quality of life. Unfortunately, most patients are diagnosed with late stage HCC where only palliative treatment is available. Therefore, biomarkers which could detect HCC early with a high degree of sensitivity and specificity, may play a crucial role in the diagnosis and management of the disease. This review will aim to provide an overview of the different biomarkers of HCC comprising those used in the diagnosis of HCC in at risk populations, as well as others with potential for prognosis, risk predisposition and prediction of response to therapeutic intervention.
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Affiliation(s)
- Gurjot Singh
- Department of Medicine, University of British Columbia, Vancouver V5Z 1M9, Canada
| | - Eric M Yoshida
- Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver V5Z 1M9, Canada
| | - Sahaj Rathi
- Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver V5Z 1M9, Canada
| | - Vladimir Marquez
- Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver V5Z 1M9, Canada
| | - Peter Kim
- Division of Oncological Surgery, Department of Medicine, University of British Columbia, Vancouver V5Z 1M9, Canada
| | - Siegfried R Erb
- Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver V5Z 1M9, Canada
| | - Baljinder S Salh
- Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver V5Z 1M9, Canada
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Identification of snoRNA SNORA71A as a Novel Biomarker in Prognosis of Hepatocellular Carcinoma. DISEASE MARKERS 2020; 2020:8879944. [PMID: 33062075 PMCID: PMC7537701 DOI: 10.1155/2020/8879944] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Revised: 08/02/2020] [Accepted: 09/10/2020] [Indexed: 12/21/2022]
Abstract
Background Small nucleolar RNAs (snoRNAs) have been proved to play important roles in various cellular physiological process. Recently, dysregulation of snoRNA SNORA71A has been found involved in tumorigenesis of various malignant cancers. However, the emerging effects of SNORA71A in hepatocellular carcinoma (HCC) remain largely unclear. In this study, we aimed to explore the SNORA71A expression and its underlying significance in HCC. Methods Expression of SNORA71A in cell lines and clinical specimens was measured by quantitative real-time PCR. Then, all enrolled HCC patients were divided into low and high SNORA71A expression subgroups and then they were compared in the aspects of clinical features as well as survival outcome by respective statistical analysis methods. Results SNORA71A was significantly downexpressed in SK-HEP-1 (P = 0.001), Huh-7 (P < 0.001), Hep3B (P < 0.001), and clinical HCC specimens (P = 0.006). Comparing the clinical features between SNORA71A expression subgroups, it showed that low SNORA71A expression was significantly associated with large tumor diameter, multiple lesions, capsular invasion, bad tumor differentiation, and TNM stage (P < 0.05). Furthermore, it was found that HCC patients with lower SNORA71A expression had higher risk in postoperative tumor relapse (median time: 9.5 vs. 35.2 months; low vs. high; P < 0.001) and poor overall survival (median time: 36.8 vs. 52.9 months; low vs. high; P < 0.001). Besides, SNORA71A expression served as independent risk factors for tumor-free (HR = 0.450; 95% CI [0.263-0.770]; P = 0.004) and long-term survival (HR = 0.289; 95% CI [0.127-0.657]; P = 0.003). Conclusions Our study for the first time demonstrated that downregulation of SNORA71A could serve as a novel biomarker for clinical assessment and prognostic prediction of HCC patients.
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Cao P, Jin Q, Feng L, Li H, Qin G, Zhou G. Emerging roles and potential clinical applications of noncoding RNAs in hepatocellular carcinoma. Semin Cancer Biol 2020; 75:136-152. [PMID: 32931952 DOI: 10.1016/j.semcancer.2020.09.003] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Revised: 08/24/2020] [Accepted: 09/01/2020] [Indexed: 12/12/2022]
Abstract
Hepatocellular carcinoma(HCC) is one of the most common forms of cancer, and accounts for a high proportion of cancer-associated deaths. Growing evidences have demonstrated that non- protein-coding regions of the genome could give rise to transcripts, termed noncoding RNA (ncRNA), that form novel functional layers of the cellular activity. ncRNAs are implicated in different molecular mechanisms and functions at transcriptional, translational and post-translational levels. An increasing number of studies have demonstrated a complex array of molecular and cellular functions of ncRNAs in different stages of the HCC tumorigenesis, either in an oncogenic or tumor-suppressive manner. As a result, several pre-clinical studies have highlighted the great potentials of ncRNAs as novel biomarkers for cancer diagnosis or therapeutics in targeting HCC progression. In this review, we briefly described the characteristics of several representative ncRNAs and summarized the latest findings of their roles and mechanisms in the development of HCC, in order to better understand the cancer biology and their potential clinical applications in this malignancy.
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Affiliation(s)
- Pengbo Cao
- State Key Laboratory of Proteomics, National Center for Protein Sciences at Beijing, Beijing Institute of Radiation Medicine, Beijing, China
| | - Qian Jin
- State Key Laboratory of Proteomics, National Center for Protein Sciences at Beijing, Beijing Institute of Radiation Medicine, Beijing, China
| | - Lan Feng
- State Key Laboratory of Proteomics, National Center for Protein Sciences at Beijing, Beijing Institute of Radiation Medicine, Beijing, China
| | - Haibei Li
- Key Laboratory of Risk Assessment and Control for Environment & Food Safety, Tianjin Institute of Environmental & Operational Medicine, Tianjin City, China
| | - Geng Qin
- State Key Laboratory of Rare Earth Resources Utilization and Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun City, China
| | - Gangqiao Zhou
- State Key Laboratory of Proteomics, National Center for Protein Sciences at Beijing, Beijing Institute of Radiation Medicine, Beijing, China; Collaborative Innovation Center for Personalized Cancer Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing City, China; Medical College, Guizhou University, Guiyang City, China.
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Onyirioha K, Mittal S, G Singal A. Is hepatocellular carcinoma surveillance in high-risk populations effective? Hepat Oncol 2020; 7:HEP25. [PMID: 32774835 PMCID: PMC7399579 DOI: 10.2217/hep-2020-0012] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Accepted: 06/23/2020] [Indexed: 02/07/2023] Open
Abstract
Several professional societies recommend hepatocellular carcinoma (HCC) surveillance in high-risk patients including patients with cirrhosis from any etiology and subsets of noncirrhotic chronic hepatitis B virus infection. The efficacy of HCC surveillance to increase early detection and improve survival has been demonstrated in a large randomized controlled trial among hepatitis B virus patients and several cohort studies among those with cirrhosis. However, the effectiveness on HCC surveillance, when applied in clinical practice, is lower due to low utilization of HCC surveillance among at-risk patients, poorer test performance given operator dependency and differences in patient characteristics, and downstream process failures such as treatment delays. Interventions to increase surveillance utilization and improve surveillance test performance should improve surveillance effectiveness in the future.
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Affiliation(s)
- Kristeen Onyirioha
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA
| | - Sukul Mittal
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA
| | - Amit G Singal
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA
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