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Fassio E, Colombato L, Gualano G, Perez S, Puga-Tejada M, Landeira G. Hepatocellular Carcinoma After HCV Eradication with Direct-Acting Antivirals: A Reappraisal Based on New Parameters to Assess the Persistence of Risk. Cancers (Basel) 2025; 17:1018. [PMID: 40149352 PMCID: PMC11940336 DOI: 10.3390/cancers17061018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2025] [Revised: 03/12/2025] [Accepted: 03/16/2025] [Indexed: 03/29/2025] Open
Abstract
Approximately 95% of patients with chronic hepatitis C achieve viral eradication through direct-acting antiviral (DAA) treatment. Ensuing clinical benefits include halting liver fibrosis, thereby reducing the need for liver transplantation, and decreasing both liver-related and overall mortality. It is well established that, although ameliorated, the risk of developing hepatocellular carcinoma (HCC) persists, particularly among patients with pre-treatment advanced fibrosis/cirrhosis. Current guidelines recommend indefinite HCC surveillance in these patients. However, a recent Markov model evaluation shows that HCC surveillance is cost-effective only for patients with cirrhosis but not so for those with F3 fibrosis, a finding which points out the need to better define the risk of HCC in hepatitis C patients after cure and further characterize pre- and post-treatment factors that might affect the incidence of HCC in this setting. We reviewed the literature analyzing this aspect. Here we summarize the main findings: male gender and older age are independent predictors of increased risk of post-cure HCC development. Moreover, non-invasive tests for hepatic fibrosis, namely FIB4, APRI, and liver stiffness, measured before and after treatment and their post-therapy change, contribute to better stratifying the risk of HCC occurrence. Furthermore, low serum albumin, as well as an AFP above 7 ng/mL prior to and after DAA therapy, also constitute independent predictors of HCC development. Considering these findings, we propose to classify patients with HCV viral eradication and advanced fibrosis/cirrhosis into groups of low, medium, or high risk of HCC and to adopt adequate surveillance strategies for each group, including protocols for abbreviated magnetic resonance imaging (MRI) for those at the highest risk.
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Affiliation(s)
- Eduardo Fassio
- Liver Section, Gastroenterology Service, Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires 1684, Argentina; (S.P.); (G.L.)
| | - Luis Colombato
- Hospital Británico de Buenos Aires, Buenos Aires 1280, Argentina;
| | - Gisela Gualano
- Hospital Regional Dr. Ramón Carrillo, Santiago del Estero 4200, Argentina;
| | - Soledad Perez
- Liver Section, Gastroenterology Service, Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires 1684, Argentina; (S.P.); (G.L.)
| | - Miguel Puga-Tejada
- Instituto Ecuatoriano de Enfermedades Digestivas, Guayaquil 090505, Ecuador;
| | - Graciela Landeira
- Liver Section, Gastroenterology Service, Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires 1684, Argentina; (S.P.); (G.L.)
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Patel S, Khalili M, Singal AG, Pinheiro PS, Jones PD, Kim RG, Kode V, Thiemann A, Zhang W, Cheung R, Wong RJ. Significant Disparities in Hepatocellular Carcinoma Outcomes by Race/Ethnicity and Sociodemographic Factors. Cancer Epidemiol Biomarkers Prev 2025; 34:355-365. [PMID: 39636161 PMCID: PMC11802308 DOI: 10.1158/1055-9965.epi-24-1094] [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: 07/26/2024] [Revised: 09/30/2024] [Accepted: 12/02/2024] [Indexed: 12/07/2024] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) disproportionately affects racial/ethnic minorities. We evaluated the impact of income and geography on racial/ethnic disparities across the HCC care cascade in the United States. METHODS Using NCI registry data spanning 2000 to 2020, adults with HCC were evaluated to determine race/ethnicity-specific differences in tumor stage at diagnosis, delays and gaps in treatment, and survival. Adjusted regression models evaluated predictors of HCC outcomes. RESULTS Among 112,389 adults with HCC, cohort characteristics were as follows: 49.8% non-Hispanic White (NHW), 12.0% African American(AA), 20.5% Hispanic, 16.5% Asian/Pacific Islander, and 1.1% American Indian/Alaska Native. Compared with NHW patients, AA patients had lower odds of localized-stage HCC at diagnosis [adjusted odds ratio (aOR), 0.84], lower odds of HCC treatment receipt (aOR, 0.77), greater odds of treatment delays (aOR, 1.12), and significantly greater risk of death [adjusted hazards ratio (aHR), 1.10]. Compared with NHW patients from large metro areas, AA patients from large metro areas had 8% higher mortality risk (aHR, 1.08), whereas AA patients from small-medium metro areas had 17% higher mortality risk (aHR, 1.17; all P < 0.05). CONCLUSIONS Among a population-based cohort of US adults with HCC, significant race/ethnicity-specific disparities across the HCC care continuum were observed. Lower household income and more rural geography among racial/ethnic minorities are also associated with disparities in HCC outcomes, particularly among AA patients. IMPACT Our study shows that lower income and less urban/more rural geography among racial/ethnic minorities are also associated with disparities in HCC outcomes, particularly among AA patients with HCC. This contextualizes the complex relationship between sociodemographic factors and HCC outcomes through an intersectional lens.
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Affiliation(s)
- Shyam Patel
- Department of Medicine, California Pacific Medical Center, San Francisco, CA
| | - Mandana Khalili
- Department of Medicine, Division of Gastroenterology and Hepatology, University of California, San Francisco, San Francisco, CA
| | - Amit G. Singal
- Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX
| | - Paulo S. Pinheiro
- Division of Epidemiology & Population Health Sciences, Department of Public Health Sciences, University of Miami School of Medicine, Miami, FL
| | - Patricia D. Jones
- Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami School of Medicine, Miami, FL
| | - Rebecca G. Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Utah Health, Salt Lake City, UT
| | - Vishwajit Kode
- Department of Medicine, California Pacific Medical Center, San Francisco, CA
| | - Anna Thiemann
- Department of Medicine, California Pacific Medical Center, San Francisco, CA
| | - Wei Zhang
- Gastroenterology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Ramsey Cheung
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Palo Alto, CA
- Gastroenterology Section, Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA
| | - Robert J. Wong
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Palo Alto, CA
- Gastroenterology Section, Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA
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Jiang J, Bouquet E, Kweon Y, Elsaid MI, Diaz DA, Conteh L, Sobotka LA. Neighborhood opportunity is associated with completion of hepatocellular carcinoma surveillance prior to the diagnosis of hepatocellular carcinoma in patients with cirrhosis. Clin Res Hepatol Gastroenterol 2024; 48:102485. [PMID: 39489339 DOI: 10.1016/j.clinre.2024.102485] [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: 07/16/2024] [Revised: 10/09/2024] [Accepted: 10/19/2024] [Indexed: 11/05/2024]
Abstract
BACKGROUND The Ohio Opportunity Index (OOI) is a multidimensional metric used to quantify neighborhood-level resources to access a wide array of factors that influence health. This study examined the relationship between neighborhood opportunity and completion of guideline-concordant hepatocellular carcinoma (HCC) screening in patients with cirrhosis. METHODS This retrospective study included patients with cirrhosis and HCC who received care at The Ohio State University Wexner Medical Center between 1/1/2015 and 12/31/2021. High opportunity was defined as a score greater than the third quartile of the study cohort. Modified Poisson regression models with robust variance examined the association, on the prevalence ratio (aPR) scale, between guideline-concordant HCC screening and high neighborhood opportunity status. RESULTS This study included 157 cirrhosis patients newly diagnosed with HCC. Only 25.5 % of the patients completed HCC surveillance within 6 months prior to diagnosis. The OOI was a significant predictor of adherence in all models. For every ten-percentile increase in OOI score, there was a consistent increase in the prevalence ratio (PR) of pre-diagnosis HCC surveillance (PR=1.37, 95 % CI 1.10-1.71). This effect remained significant after controlling for sociodemographic, clinical, and cirrhosis-related variables (adjusted PR=1.38, 95 % CI 1.02-1.85. Compared to those with high OOI (i.e.,≥Q3), patients in the lowest opportunity quartile had a 64 % lower prevalence of HCC screening (PR=0.36, 95 % CI 0.26-0.50). CONCLUSION Neighborhood opportunity status has a dose-dependent effect on HCC surveillance adherence in patients with cirrhosis. Future studies should identify neighborhood-level interventions to reduce socioeconomic disparities in HCC diagnosis and outcomes.
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Affiliation(s)
- Joanna Jiang
- Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Erin Bouquet
- Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Yesung Kweon
- Center for Biostatistics, The Ohio State University, Columbus, OH, USA
| | - Mohamed I Elsaid
- Center for Biostatistics, The Ohio State University, Columbus, OH, USA; Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, OH, USA; Division of Medical Oncology, College of Medicine, The Ohio State University, Columbus, OH, USA
| | - Dayssy A Diaz
- Department of Radiation Oncology, The Ohio State University Medical Center, Columbus, OH, USA
| | - Lanla Conteh
- Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Lindsay A Sobotka
- Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
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Zeng RW, Ong CEY, Ong EYH, Chung CH, Lim WH, Xiao J, Danpanichkul P, Law JH, Syn N, Chee D, Kow AWC, Lee SW, Takahashi H, Kawaguchi T, Tamaki N, Dan YY, Nakajima A, Wijarnpreecha K, Muthiah MD, Noureddin M, Loomba R, Ioannou GN, Tan DJH, Ng CH, Huang DQ. Global Prevalence, Clinical Characteristics, Surveillance, Treatment Allocation, and Outcomes of Alcohol-Associated Hepatocellular Carcinoma. Clin Gastroenterol Hepatol 2024; 22:2394-2402.e15. [PMID: 38987014 DOI: 10.1016/j.cgh.2024.06.026] [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: 03/11/2024] [Revised: 05/25/2024] [Accepted: 06/02/2024] [Indexed: 07/12/2024]
Abstract
BACKGROUND Although the burden of alcohol-associated hepatocellular carcinoma (HCC) is increasing with rising alcohol consumption, clinical presentation and outcomes of alcohol-associated HCC have not been systematically assessed. We aimed to determine the prevalence, clinical characteristics, surveillance rates, treatment allocation, and outcomes of alcohol-associated HCC. METHODS Medline and Embase were searched from inception to January 2023. Proportional data were analyzed using a generalized linear mixed model. The odds ratio (OR) or mean difference comparing alcohol-associated HCC and other causes was obtained with pairwise meta-analysis. Survival outcomes were evaluated using a pooled analysis of hazard ratios. RESULTS Of 4824 records identified, 55 articles (86,345 patients) were included. Overall, 30.4% (95% confidence interval [CI], 24.0%-37.7%) of HCC was alcohol associated, with the highest proportion in Europe and the lowest in the Americas. People with alcohol-associated HCC were more likely male but were similar in age and comorbidities compared with other causes. A total of 20.8% (95% CI, 11.4%-34.9%) of people with alcohol-associated HCC underwent surveillance compared with 35.0%, 31.6%, and 21.4% in hepatitis B virus, hepatitis C virus, and metabolic dysfunction-associated HCC, respectively (all P < .05). Alcohol-associated HCC had a lower likelihood of Barcelona Clínic Liver Cancer C stage (0/A) (OR, 0.7; 95% CI, 0.6-0.9; P = .018) and curative therapy (24.5% vs 33.9%; OR, 0.7; 95% CI, 0.5-0.9; P = .003), and higher mortality (HR, 1.3; 95% CI, 1.1-1.5; P = .012) when compared with other causes. CONCLUSIONS Alcohol-associated HCC is associated with lower surveillance rates, more advanced BCLC stage, lower likelihood of receiving curative therapy, and poorer survival. These data call for measures to reduce heavy alcohol consumption and improve strategies for effective HCC surveillance in high-risk individuals.
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Affiliation(s)
| | - Christen En Ya Ong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Elden Yen Hng Ong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Charlotte Hui Chung
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Wen Hui Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Jieling Xiao
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | | | - Jia Hao Law
- Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, National University Hospital, Singapore
| | - Nicholas Syn
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Biostatistics & Modelling Domain, Saw Swee Hock School of Public Health, National University of Singapore, Singapore
| | - Douglas Chee
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore
| | - Alfred Wei Chieh Kow
- Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, National University Hospital, Singapore; Division of Surgical Oncology, National University Cancer Institute, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Sung Won Lee
- Division of Hepatology, Department of Internal Medicine, Catholic University of Korea, Seoul, Republic of Korea
| | | | - Takumi Kawaguchi
- Department of Digestive Disease Information & Research, School of Medicine, Kurume University, Fukuoka, Japan
| | - Nobuharu Tamaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yock Young Dan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Atsushi Nakajima
- Graduate School of Medicine, Yokohama City University, Yokohama, Japan
| | - Karn Wijarnpreecha
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Arizona College of Medicine, Phoenix, Arizona; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Banner University Medical Center, Phoenix, Arizona
| | - Mark D Muthiah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore
| | | | - Rohit Loomba
- NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, California
| | - George N Ioannou
- Division of Gastroenterology, Department of Medicine, Veterans Affairs Puget Sound Health Care System, Seattle, Washington; Division of Gastroenterology, Department of Medicine, University of Washington, Seattle, Washington
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Cheng Han Ng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Digestive Disease Information & Research, School of Medicine, Kurume University, Fukuoka, Japan
| | - Daniel Q Huang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore.
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5
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Ho JKH, Thurairajah PH, Huang DQ, Fan KH. The Rising Burden of Hepatocellular Carcinoma: Is the Gender Gap Narrowing? J Clin Transl Hepatol 2024; 12:763-764. [PMID: 39280068 PMCID: PMC11393844 DOI: 10.14218/jcth.2024.00216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 07/25/2024] [Accepted: 07/26/2024] [Indexed: 09/18/2024] Open
Affiliation(s)
- James K H Ho
- Division of Gastroenterology and Hepatology, National University Hospital, National University Health System, Singapore, Singapore
| | - Prem H Thurairajah
- Division of Gastroenterology and Hepatology, National University Hospital, National University Health System, Singapore, Singapore
| | - Daniel Q Huang
- Division of Gastroenterology and Hepatology, National University Hospital, National University Health System, Singapore, Singapore
| | - Kristie H Fan
- Division of Gastroenterology and Hepatology, National University Hospital, National University Health System, Singapore, Singapore
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Stylianos SL, Goel CR, Lee RM, Yopp A, Kronenfeld J, Goel N, Datta J, Lee A, Silberfein E, Russell MC. Comparing barriers to early stage diagnosis of hepatocellular carcinoma between safety net hospitals and academic medical centers: An analysis from the United States Safety-Net Collaborative. J Surg Oncol 2024; 130:493-503. [PMID: 39087490 DOI: 10.1002/jso.27787] [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: 11/07/2023] [Revised: 05/15/2024] [Accepted: 07/20/2024] [Indexed: 08/02/2024]
Abstract
BACKGROUND AND OBJECTIVES Early detection of hepatocellular carcinoma (HCC) is associated with improved survival. However, a greater proportion of patients treated at safety net hospitals (SNHs) present with late-stage disease compared to those at academic medical centers (AMCs). This study aims to identify barriers to diagnosis of HCC, highlighting differences between SNHs and AMCs. METHODS The US Safety Net Collaborative-HCC database was queried. Patients were stratified by facility of diagnosis (SNH or AMC). Patient demographics and HCC screening rates were examined. The primary outcome was stage at diagnosis (AJCC I/II-"early"; AJCC III/IV-"late"). RESULTS 1290 patients were included; 50.2% diagnosed at SNHs and 49.8% at AMCs. At SNHs, 44.4% of patients were diagnosed late, compared to 27.6% at AMCs. On multivariable regression, Black race was associated with late diagnosis in both facilities (SNH: odds ratio 1.96, p = 0.03; AMC: 2.27, <0.01). Screening was associated with decreased odds of late diagnosis (SNH: 0.46, p = 0.04; AMC: 0.37, p < 0.01). CONCLUSIONS Black race was associated with late diagnosis of HCC, while screening was associated with early diagnosis across institutional types. These results suggest socially constructed racial bias in screening and diagnosis of HCC. Screening efforts targeting SNH patients and Black patients at all facilities are essential to reduce disparities.
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Affiliation(s)
- Sophia L Stylianos
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA
| | - Caroline R Goel
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA
| | - Rachel M Lee
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA
| | - Adam Yopp
- Division of Surgical Oncology, Department of Surgery, University of Texas Southwestern Medical School, Dallas, Texas, USA
| | - Joshua Kronenfeld
- Division of Surgical Oncology, Department of Surgery, University of Miami Medical School, Miami, Florida, USA
| | - Neha Goel
- Division of Surgical Oncology, Department of Surgery, University of Miami Medical School, Miami, Florida, USA
| | - Jashodeep Datta
- Division of Surgical Oncology, Department of Surgery, University of Miami Medical School, Miami, Florida, USA
| | - Ann Lee
- Division of Surgical Oncology, Department of Surgery, New York University Medical School, New York, New York, USA
| | - Eric Silberfein
- Division of Surgical Oncology, Department of Surgery, Baylor College of Medicine, Houston, Texas, USA
| | - Maria C Russell
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA
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Feng GH, Yue QQ, Zhao KH, Peng T, Tang T, Sun YX, Meng XR, Huang LL, Zeng X, Zeng Y. Factors affecting the compliance of hepatocellular carcinoma screening among high-risk populations: A systematic review and meta-analysis. Public Health Nurs 2024; 41:476-486. [PMID: 38468509 DOI: 10.1111/phn.13298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Revised: 01/25/2024] [Accepted: 02/22/2024] [Indexed: 03/13/2024]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third leading cause of cancer mortality. HCC has high morbidity, high mortality, and low survival rates. Screening is one of the most significant methods of lowering incidence and death while also increasing survival. OBJECTIVES The aim of this study was to identify the facilitators and barriers to participation in HCC screening among high-risk populations. METHODS A comprehensive and systematic search was undertaken in PubMed, Web of Science, MEDLINE, EMBACE, EBSCOhost and the Cochrane Library. A combination of synonyms of the keywords including HCC, screening, factors and adherence were used for searching. Studies addressing the facilitators and barriers to HCC screening compliance in at-risk individuals were included. Data were synthesized using Review Manager version 5.4. A random/fixed effects model meta-analysis was performed to estimate the pooled data and expressed with odds ratio (OR) and 95% confidence interval (CI). RESULTS A total of seven articles met the inclusion criteria. Qualitative (n = 1) and quantitative (n = 6) studies using various types of surgery were conducted. The most commonly mentioned barriers were insufficient knowledge and awareness of HCC screening, unawareness of the necessity for early detection of HCC and lack of physician recommendation. A meta-analysis of seven studies showed that individuals with a family history of HCC increased screening uptake by nearly three times (OR: 2.69, 95% CI: 1.93, 3.75). Other most frequently reported facilitators include age, education level, and perceived risk et al. CONCLUSIONS Many barriers to HCC screening were found. Meanwhile, this review points out that improving the awareness of high-risk populations toward HCC screening is expected to enhance compliance, thereby promoting early diagnosis of liver cancer, reducing mortality, and alleviating the burden of HCC.
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Affiliation(s)
- Ge-Hui Feng
- Department of International and Humanistic Nursing, Hunan Science Popularization Education Base, School of Nursing, Hengyang Medical School, University of South China, Hengyang, China
| | - Qian-Qian Yue
- Department of International and Humanistic Nursing, Hunan Science Popularization Education Base, School of Nursing, Hengyang Medical School, University of South China, Hengyang, China
| | - Ke-Hao Zhao
- Department of International and Humanistic Nursing, Hunan Science Popularization Education Base, School of Nursing, Hengyang Medical School, University of South China, Hengyang, China
| | - Tong Peng
- Department of International and Humanistic Nursing, Hunan Science Popularization Education Base, School of Nursing, Hengyang Medical School, University of South China, Hengyang, China
| | - Tian Tang
- Department of International and Humanistic Nursing, Hunan Science Popularization Education Base, School of Nursing, Hengyang Medical School, University of South China, Hengyang, China
| | - Ying-Xue Sun
- Department of International and Humanistic Nursing, Hunan Science Popularization Education Base, School of Nursing, Hengyang Medical School, University of South China, Hengyang, China
| | - Xin-Ru Meng
- Department of International and Humanistic Nursing, Hunan Science Popularization Education Base, School of Nursing, Hengyang Medical School, University of South China, Hengyang, China
| | - Li-Li Huang
- Department of International and Humanistic Nursing, Hunan Science Popularization Education Base, School of Nursing, Hengyang Medical School, University of South China, Hengyang, China
| | - Xi Zeng
- Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Cancer Research Institute; Hengyang Medical School, University of South China, Hengyang, China
| | - Ying Zeng
- Department of International and Humanistic Nursing, Hunan Science Popularization Education Base, School of Nursing, Hengyang Medical School, University of South China, Hengyang, China
- Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Cancer Research Institute; Hengyang Medical School, University of South China, Hengyang, China
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8
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Wong RJ, Jones PD, Niu B, Therapondos G, Thamer M, Kshirsagar O, Zhang Y, Pinheiro P, Kyalwazi B, Fass R, Khalili M, Singal AG. Clinician-Level Knowledge and Barriers to Hepatocellular Carcinoma Surveillance. JAMA Netw Open 2024; 7:e2411076. [PMID: 38743424 PMCID: PMC11094557 DOI: 10.1001/jamanetworkopen.2024.11076] [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: 12/22/2023] [Accepted: 03/12/2024] [Indexed: 05/16/2024] Open
Abstract
Importance Surveillance for hepatocellular carcinoma (HCC) in patients with cirrhosis is underused. Identifying potentially modifiable factors to address barriers in HCC surveillance is critical to improve patient outcomes. Objective To evaluate clinician-level factors contributing to underuse of HCC surveillance in patients with cirrhosis. Design, Setting, and Participants This survey study included primary care clinicians (PCCs) and gastroenterology and hepatology clinicians at 5 safety-net health systems in the US. Clinicians were surveyed from March 15 to September 15, 2023, to assess knowledge, attitudes, beliefs, perceived barriers, and COVID-19-related disruptions in HCC surveillance in patients with cirrhosis. Data were analyzed from October to November 2023. Main Outcome and Measures HCC surveillance knowledge was assessed with 6 questions querying the respondent's ability to correctly identify appropriate use of HCC surveillance. Attitudes, perceived barriers, and beliefs regarding HCC surveillance and perceived impact of the COVID-19 pandemic-related disruptions with HCC surveillance were assessed with a series of statements using a 4-point Likert scale and compared PCCs and gastroenterology and hepatology clinicians. Results Overall, 347 of 1362 clinicians responded to the survey (25.5% response rate), among whom 142 of 237 (59.9%) were PCCs, 48 of 237 (20.3%) gastroenterology and hepatology, 190 of 236 (80.5%) were doctors of medicine and doctors of osteopathic medicine, and 46 of 236 (19.5%) were advanced practice clinicians. On HCC knowledge assessment, 144 of 270 (53.3%) scored 5 or more of 6 questions correctly, 37 of 48 (77.1%) among gastroenterology and hepatology vs 65 of 142 (45.8%) among PCCs (P < .001). Those with higher HCC knowledge scores were less likely to report barriers to HCC surveillance. PCCs were more likely to report inadequate time to discuss HCC surveillance (37 of 139 [26.6%] vs 2 of 48 [4.2%]; P = .001), difficulty identifying patients with cirrhosis (82 of 141 [58.2%] vs 5 of 48 [10.4%]; P < .001), and were not up-to-date with HCC surveillance guidelines (87 of 139 [62.6%] vs 5 of 48 [10.4%]; P < .001) compared with gastroenterology and hepatology clinicians. While most acknowledged delays during the COVID-19 pandemic, 62 of 136 PCCs (45.6%) and 27 of 45 gastroenterology and hepatology clinicians (60.0%) reported that patients with cirrhosis could currently complete HCC surveillance without delays. Conclusions and Relevance In this survey study, important gaps in knowledge and perceived barriers to HCC surveillance were identified. Effective delivery of HCC education to PCCs and health system-level interventions must be pursued in parallel to address the complex barriers affecting suboptimal HCC surveillance in patients with cirrhosis.
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Affiliation(s)
- Robert J. Wong
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine and Gastroenterology Section, Veterans Affairs Palo Alto Healthcare System, Palo Alto, California
| | - Patricia D. Jones
- Division of Digestive Health and Liver Diseases, University of Miami School of Medicine and Jackson Memorial Health System, Miami, Florida
| | - Bolin Niu
- Division of Gastroenterology and Hepatology, MetroHealth Hospital and Health System, Cleveland, Ohio
| | | | - Mae Thamer
- Medical Technology and Practice Patterns Institute, Bethesda, Maryland
| | - Onkar Kshirsagar
- Medical Technology and Practice Patterns Institute, Bethesda, Maryland
| | - Yi Zhang
- Medical Technology and Practice Patterns Institute, Bethesda, Maryland
| | - Paulo Pinheiro
- Division of Epidemiology and Population Health Sciences, University of Miami School of Medicine, Miami, Florida
| | - Beverly Kyalwazi
- Department of Medicine, University of Texas Southwestern Medical Center, Dallas
| | - Ronnie Fass
- Division of Gastroenterology and Hepatology, MetroHealth Hospital and Health System, Cleveland, Ohio
| | - Mandana Khalili
- Division of Gastroenterology and Hepatology, University of California San Francisco and Zuckerberg San Francisco General Hospital, San Francisco
| | - Amit G. Singal
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center and Parkland Health, Dallas
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9
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Lin D, Tan R, Teigland C, Hernandez S, Kim S, Kilgore KM. Race/ethnicity and socioeconomic position in emergency department utilization in patients with hepatocellular carcinoma. Future Oncol 2024; 20:1765-1777. [PMID: 38639552 PMCID: PMC11486108 DOI: 10.2217/fon-2023-0412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Accepted: 03/01/2024] [Indexed: 04/20/2024] Open
Abstract
Aim: Evaluate the association of race/ethnicity and socioeconomic position (SEP) on emergency department (ED) visits for patients with hepatocellular carcinoma (HCC), which may reflect access to and quality of cancer care.Materials & methods: Patients with HCC identified from a commercial multi-payer claims database between 2015 and 2018 were matched to near-neighborhood social determinants of health (SDOH) and stratified by race/ethnicity and SEP (proxied by annual household income). Analyses evaluated the effect of race/ethnicity and SEP on ED utilization, adjusting for SDOH, demographic and clinical characteristics using multivariable regression methods.Results: A total of 22,247 patients were included. Black and Hispanic patients had 43 and 18% higher ED utilization than White patients at higher-income levels (p < 0.01); these differences were nonsignificant at lower-income. Regardless of income level, Asian patients had lower ED utilization.Conclusion: Further research on the intersectionality between race/ethnicity, SEP and other SDOH may guide structural-level interventions to address health inequities.
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Affiliation(s)
- Daniel Lin
- Department of Medical Oncology, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Ruoding Tan
- Public Affairs and Access, Genentech, Inc., South San Francisco, CA 94080, USA
| | - Christie Teigland
- Research Science and Advanced Analytics, Inovalon, Inc. Bowie, MD 20716, USA
| | - Sairy Hernandez
- Public Affairs and Access, Genentech, Inc., South San Francisco, CA 94080, USA
| | - Seung Kim
- Research Science and Advanced Analytics, Inovalon, Inc. Bowie, MD 20716, USA
| | - Karl M Kilgore
- Research Science and Advanced Analytics, Inovalon, Inc. Bowie, MD 20716, USA
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10
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Abboud Y, Ismail M, Khan H, Medina-Morales E, Alsakarneh S, Jaber F, Pyrsopoulos NT. Hepatocellular Carcinoma Incidence and Mortality in the USA by Sex, Age, and Race: A Nationwide Analysis of Two Decades. J Clin Transl Hepatol 2024; 12:172-181. [PMID: 38343612 PMCID: PMC10851066 DOI: 10.14218/jcth.2023.00356] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 10/27/2023] [Accepted: 12/15/2023] [Indexed: 07/26/2024] Open
Abstract
BACKGROUND AND AIMS While the incidence rates of hepatocellular carcinoma (HCC) are increasing, there are limited comprehensive data on demographic-specific incidence and mortality trends in the USA. We aimed to evaluate recent trends in HCC incidence and mortality among different demographic groups in the USA. METHODS Age-adjusted HCC incidence rates were calculated from the Centers for Disease Control's United States Cancer Statistics database, which combines incidence data on newly diagnosed cancer cases and covers approximately 98% of the population in the USA. Additionally, age-adjusted HCC mortality rates were obtained from the Centers for Disease Control's National Center for Health Statistics database, which offers comprehensive coverage spanning nearly 100% of deaths attributed to HCC in the USA. Rates were stratified by sex, age (older [≥55 years] and younger [<55 years] adults), race and ethnicity (Non-Hispanic White, Non-Hispanic Black, Hispanic, Non-Hispanic Asian/Pacific Islander, and Non-Hispanic American Indian/Alaska Native), and tumor stage at diagnosis (early and late). Annual and average annual percentage change (AAPC) were calculated using joinpoint regression. A sex-specific pairwise comparison was conducted. RESULTS Between 2001 and 2020, there were 467,346 patients diagnosed with HCC (26.0% women), with increasing incidence in both sexes without significant difference (p=0.65). In younger adults (78,169 patients), the incidence decreased in men but not in women (AAPC difference=-2.39, p=0.002). This was seen in various racial and ethnic groups, mostly driven by early-stage tumors (AAPC difference=-2.65, p=0.02). There were 329,973 deaths attributed to HCC between 2000 and 2020 (28.4% women). In younger adults (43,093 deaths), mortality decreased in men at a greater rate than in women (AAPC difference=1.61, p=0.007). This was seen in various racial and ethnic groups, most notably in non-Hispanic American Indian/Alaska Natives (AAPC difference=-4.51, p=0.01). CONCLUSIONS Nationwide USA data, covering nearly all HCC cases, show an increasing incidence and mortality over the last two decades. In younger adults, there was a decreasing incidence in men but not in women, due to early-stage tumors. Mortality improved in younger men at a greater rate than in women, especially in Non-Hispanic American Indian/Alaska Natives. Future studies are warranted to identify the risk factors associated with the occurrence and outcomes of HCC in demographic-specific populations, especially younger women.
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Affiliation(s)
- Yazan Abboud
- Department of Internal Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA
| | - Mohamed Ismail
- Department of Internal Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA
| | - Hamza Khan
- Department of Internal Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA
| | - Esli Medina-Morales
- Department of Internal Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA
| | - Saqr Alsakarneh
- Department of Internal Medicine, University of Missouri-Kansas City, Kansas City, MO, USA
| | - Fouad Jaber
- Department of Internal Medicine, University of Missouri-Kansas City, Kansas City, MO, USA
| | - Nikolaos T. Pyrsopoulos
- Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ, USA
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11
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Shaltiel T, Sarpel U, Branch AD. The adverse characteristics of hepatocellular carcinoma in the non-cirrhotic liver disproportionately disadvantage Black patients. Cancer Med 2024; 13:e6654. [PMID: 38230878 PMCID: PMC10905547 DOI: 10.1002/cam4.6654] [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: 04/17/2023] [Revised: 08/24/2023] [Accepted: 10/12/2023] [Indexed: 01/18/2024] Open
Abstract
BACKGROUND Black patients have higher hepatocellular carcinoma (HCC)-related mortality than White patients and more often develop HCC in non-cirrhotic liver. HCC surveillance is primarily directed toward cirrhotic patients. We aimed to characterize HCC in non-cirrhotic patients and to identify factors associated with HCC beyond Milan criteria. METHODS Demographic, imaging, laboratory, and pathology data of HCC patients at our institution, 2003-2018, were reviewed, retrospectively. Race/ethnicity were self-reported. Cirrhosis was defined as a Fibrosis-4 score ≥3.25. RESULTS Compared to 1146 cirrhotic patients, 411 non-cirrhotic patients had larger tumors (median 4.7 cm vs. 3.1 cm, p < 0.01) and were less likely to be within Milan criteria (42.6% vs. 57.7%, p < 0.01). Among non-cirrhotic patients, Black patients had larger tumors (4.9 cm vs. 4.3 cm, p < 0.01) and a higher percentage of poorly differentiated tumors (39.4% vs. 23.1%, p = 0.02). Among cirrhotic patients, Black patients had larger tumors (3.3 cm vs. 3.0 cm, p = 0.03) and were less likely to be within Milan criteria (52.3% vs. 83.2%, p < 0.01). In multivariable analysis, lack of commercial insurance (OR 1.45 [CI 95% 1.19-1.83], p < 0.01), male sex (OR 1.34 [CI 95% 1.05-1.70], p < 0.01), absence of cirrhosis (OR 1.58 [CI 95% 1.27-1.98], p < 0.01) and Black race/ethnicity (OR 1.34 [CI 95% 1.09-1.66], p = 0.01) were associated with HCC beyond Milan criteria. Black patients had lower survival rates than other patients (p < 0.01). CONCLUSIONS Non-cirrhotic patients had more advanced HCC than cirrhotic patients. Black patients (with or without cirrhosis) had more advanced HCC than comparable non-Black patients and higher mortality rates. Improved access to healthcare (commercial insurance) may increase early diagnosis (within Milan criteria) and reduce disparities.
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Affiliation(s)
- Tali Shaltiel
- Division of Surgical Oncology, Department of SurgeryIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
| | - Umut Sarpel
- Division of Surgical Oncology, Department of SurgeryIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
| | - Andrea D. Branch
- Division of Liver Diseases, Department of MedicineIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
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12
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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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13
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McEneaney LJ, Vithayathil M, Khan S. Screening, Surveillance, and Prevention of Hepatocellular Carcinoma. GASTROINTESTINAL ONCOLOGY ‐ A CRITICAL MULTIDISCIPLINARY TEAM APPROACH 2E 2024:271-290. [DOI: 10.1002/9781119756422.ch16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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14
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Choi HH, Kim S, Shum DJ, Huang CY, Shui A, Fox RK, Khalili M. Assessing Adherence to US LI-RADS Follow-up Recommendations in Vulnerable Patients Undergoing Hepatocellular Carcinoma Surveillance. Radiol Imaging Cancer 2024; 6:e230118. [PMID: 38214600 PMCID: PMC10825700 DOI: 10.1148/rycan.230118] [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: 07/18/2023] [Revised: 11/01/2023] [Accepted: 11/29/2023] [Indexed: 01/13/2024]
Abstract
Purpose To assess adherence to the US Liver Imaging Reporting and Data System (LI-RADS) recommendations for hepatocellular carcinoma (HCC) surveillance and associated patient-level factors in a vulnerable, diverse patient sample. Materials and Methods The radiology report database was queried retrospectively for patients who underwent US LI-RADS-based surveillance examinations at a single institution between June 1, 2020, and February 28, 2021. Initial US and follow-up liver imaging were included. Sociodemographic and clinical data were captured from electronic medical records. Adherence to radiologist recommendation was defined as imaging (US, CT, or MRI) follow-up in 5-7 months for US-1, imaging follow-up in 3-6 months for US-2, and CT or MRI follow-up in 2 months for US-3. Descriptive analysis and multivariable modeling that adjusted for age, sex, race, and time since COVID-19 pandemic onset were performed. Results Among 936 patients, the mean age was 59.1 years; 531 patients (56.7%) were male and 544 (58.1%) were Asian or Pacific Islander, 91 (9.7%) were Black, 129 (13.8%) were Hispanic, 147 (15.7%) were White, and 25 (2.7%) self-reported as other race. The overall adherence rate was 38.8% (95% CI: 35.7, 41.9). The most common liver disease etiology was hepatitis B (60.6% [657 of 936 patients]); 19.7% of patients (183 of 936) had current or past substance use disorder, and 44.8% (416 of 936) smoked. At adjusted multivariable analysis, older age (odds ratio [OR], 1.20; P = .02), male sex (OR, 1.62; P = .003), hepatology clinic attendance (OR, 3.81; P < .001), and recent prior US examination (OR, 2.44; P < .001) were associated with full adherence, while current smoking (OR, 0.39; P < .001) was negatively associated. Conclusion Adherence to HCC imaging surveillance was suboptimal, despite US LI-RADS implementation. Keywords: Liver, Ultrasound, Screening, Abdomen/GI, Cirrhosis, Metabolic Disorders, Socioeconomic Issues Supplemental material is available for this article. © RSNA, 2024.
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Affiliation(s)
- Hailey H. Choi
- From the Department of Radiology and Biomedical Imaging, University
of California San Francisco, Zuckerberg San Francisco General Hospital, 505
Parnassus Ave, Box 0628, Room 255, San Francisco, CA 94143 (H.H.C., D.J.S.); and
Department of Medicine, Division of General Internal Medicine (S.K., R.K.F.),
Department of Epidemiology and Biostatistics (C.Y.H., A.S.), and Department of
Medicine, Division of Gastroenterology and Hepatology (M.K.), University of
California San Francisco, San Francisco, Calif
| | - Stephanie Kim
- From the Department of Radiology and Biomedical Imaging, University
of California San Francisco, Zuckerberg San Francisco General Hospital, 505
Parnassus Ave, Box 0628, Room 255, San Francisco, CA 94143 (H.H.C., D.J.S.); and
Department of Medicine, Division of General Internal Medicine (S.K., R.K.F.),
Department of Epidemiology and Biostatistics (C.Y.H., A.S.), and Department of
Medicine, Division of Gastroenterology and Hepatology (M.K.), University of
California San Francisco, San Francisco, Calif
| | - Dorothy J. Shum
- From the Department of Radiology and Biomedical Imaging, University
of California San Francisco, Zuckerberg San Francisco General Hospital, 505
Parnassus Ave, Box 0628, Room 255, San Francisco, CA 94143 (H.H.C., D.J.S.); and
Department of Medicine, Division of General Internal Medicine (S.K., R.K.F.),
Department of Epidemiology and Biostatistics (C.Y.H., A.S.), and Department of
Medicine, Division of Gastroenterology and Hepatology (M.K.), University of
California San Francisco, San Francisco, Calif
| | - Chiung-Yu Huang
- From the Department of Radiology and Biomedical Imaging, University
of California San Francisco, Zuckerberg San Francisco General Hospital, 505
Parnassus Ave, Box 0628, Room 255, San Francisco, CA 94143 (H.H.C., D.J.S.); and
Department of Medicine, Division of General Internal Medicine (S.K., R.K.F.),
Department of Epidemiology and Biostatistics (C.Y.H., A.S.), and Department of
Medicine, Division of Gastroenterology and Hepatology (M.K.), University of
California San Francisco, San Francisco, Calif
| | - Amy Shui
- From the Department of Radiology and Biomedical Imaging, University
of California San Francisco, Zuckerberg San Francisco General Hospital, 505
Parnassus Ave, Box 0628, Room 255, San Francisco, CA 94143 (H.H.C., D.J.S.); and
Department of Medicine, Division of General Internal Medicine (S.K., R.K.F.),
Department of Epidemiology and Biostatistics (C.Y.H., A.S.), and Department of
Medicine, Division of Gastroenterology and Hepatology (M.K.), University of
California San Francisco, San Francisco, Calif
| | - Rena K. Fox
- From the Department of Radiology and Biomedical Imaging, University
of California San Francisco, Zuckerberg San Francisco General Hospital, 505
Parnassus Ave, Box 0628, Room 255, San Francisco, CA 94143 (H.H.C., D.J.S.); and
Department of Medicine, Division of General Internal Medicine (S.K., R.K.F.),
Department of Epidemiology and Biostatistics (C.Y.H., A.S.), and Department of
Medicine, Division of Gastroenterology and Hepatology (M.K.), University of
California San Francisco, San Francisco, Calif
| | - Mandana Khalili
- From the Department of Radiology and Biomedical Imaging, University
of California San Francisco, Zuckerberg San Francisco General Hospital, 505
Parnassus Ave, Box 0628, Room 255, San Francisco, CA 94143 (H.H.C., D.J.S.); and
Department of Medicine, Division of General Internal Medicine (S.K., R.K.F.),
Department of Epidemiology and Biostatistics (C.Y.H., A.S.), and Department of
Medicine, Division of Gastroenterology and Hepatology (M.K.), University of
California San Francisco, San Francisco, Calif
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15
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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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16
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Vikash S, Vikash F, Sudan A, Adal B, Kotler D. Addressing Barriers to Care in Hepatocellular Carcinoma: Promoting Equity and Access. Cureus 2023; 15:e41893. [PMID: 37581159 PMCID: PMC10423639 DOI: 10.7759/cureus.41893] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/14/2023] [Indexed: 08/16/2023] Open
Abstract
Chronic hepatitis B virus (HBV) infection is the leading cause of hepatocellular carcinoma (HCC). Chronic viral hepatitis is projected to surpass the composite mortality rates of the human immunodeficiency virus (HIV), tuberculosis, and malaria by 2040. It can be attributed to several barriers to chronic HBV infection (CHBVI) surveillance that warrant urgent attention. Here, we report a case of a 40-year-old male with CHBVI who developed HCC and underwent partial hepatic resection. However, due to an interruption in insurance and medication regimen, the patient became the victim of healthcare disparity, which led to the progression of HCC and succumbed to widespread metastasis. This case highlights and discusses the healthcare disparity and critical value of continuity of care for patients with HBV infection to promote optimal patient outcomes.
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Affiliation(s)
- Sindhu Vikash
- Department of Internal Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, USA
| | - Fnu Vikash
- Department of Internal Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, USA
| | - Aarushi Sudan
- Department of Internal Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, USA
| | - Bisrat Adal
- Department of Internal Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, USA
| | - Donald Kotler
- Department of Internal Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, USA
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17
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Kim NJ, Cravero A, VoPham T, Vutien P, Carr R, Issaka RB, Johnston J, McMahon B, Mera J, Ioannou GN. Addressing racial and ethnic disparities in US liver cancer care. Hepatol Commun 2023; 7:e00190. [PMID: 37347221 PMCID: PMC10289716 DOI: 10.1097/hc9.0000000000000190] [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: 10/31/2022] [Accepted: 05/09/2023] [Indexed: 06/23/2023] Open
Abstract
HCC, the most common form of primary liver cancer, is the fastest rising cause of cancer-related death in the United States. HCC disproportionately affects racial and ethnic minorities in the United States. A practical framework is needed to organize the complex patient, provider, health system, and societal factors that drive these racial and ethnic disparities. In this narrative review, we adapted and applied the National Institute on Minority Health and Health Disparities (NIMHD) Research Framework to the HCC care continuum, as a step toward better understanding and addressing existing HCC-related disparities. We first summarize the literature on HCC-related disparities by race and ethnicity organized by the framework's 5 domains (biological, behavioral, physical/built environment, sociocultural environment, and health care system) and 4 levels (individual, interpersonal, community, and societal) of influence. We then offer strategies to guide future research initiatives toward promotion of health equity in HCC care. Clinicians and researchers may help mitigate further inequities and better address racial and ethnic disparities in HCC care by prioritizing the following in HCC research: (1) increasing racial and ethnic minority representation, (2) collecting and reporting HCC-related data by racial and ethnic subgroups, (3) assessing the patient experience of HCC care by race and ethnicity, and (4) evaluating HCC-specific social determinants of health by race and ethnicity. These 4 priorities will help inform the development of future programs and interventions that are tailored to the unique experiences of each racial and ethnic group.
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Affiliation(s)
- Nicole J. Kim
- Division of Gastroenterology, Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Anne Cravero
- Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Trang VoPham
- Epidemiology Program, Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA
- Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington, USA
| | - Philip Vutien
- Division of Gastroenterology, Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Rotonya Carr
- Division of Gastroenterology, Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Rachel B. Issaka
- Division of Gastroenterology, Department of Medicine, University of Washington, Seattle, Washington, USA
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA
| | - Janet Johnston
- Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, Alaska
| | - Brian McMahon
- Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, Alaska
| | - Jorge Mera
- Cherokee Nation Health Services, Tahlequah, Oklahoma
| | - George N. Ioannou
- Division of Gastroenterology, Department of Medicine, University of Washington, Seattle, Washington, USA
- Division of Gastroenterology, Department of Medicine, Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA
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18
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Ying X, Pan Y, Rosenblatt R, Ng C, Sholle E, Fahoum K, Jesudian A, Fortune BE. Impact of Race and Neighborhood Socioeconomic Characteristics on Liver Cancer Diagnosis in Patients with Viral Hepatitis and Cirrhosis. J Clin Exp Hepatol 2023; 13:568-575. [PMID: 37440951 PMCID: PMC10333940 DOI: 10.1016/j.jceh.2023.01.005] [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: 11/16/2022] [Accepted: 01/06/2023] [Indexed: 07/15/2023] Open
Abstract
Background Concerning data have revealed that viral hepatitis and hepatocellular carcinoma (HCC) disproportionally impact non-White patients and those from lower socioeconomic status. A recent study found that HCC clusters were more likely to be in high poverty areas in New York City. Aims We aim to investigate the impacts of neighborhood characteristics on those with viral hepatitis and cirrhosis, particularly with advanced HCC diagnosis. Methods Patients with cirrhosis and viral hepatitis admitted to a New York City health system between 2012 and 2019 were included. Those with prior liver transplants were excluded. Neighborhood characteristics were obtained from US Census. Our primary outcome was HCC and advanced HCC diagnosis. Results This study included 348 patients; 209 without history of HCC, 20 with early HCC, 98 with advanced HCC, and 21 patients with HCC but no staging information. Patients with advanced HCC were more likely to be older, male, Asian, history of HBV, and increased mortality. They were more likely to live in areas with more foreign-born, limited English speakers, and less than high school education. After adjusting for age, sex, and payor type, Asian race and low income were independent risk factors for advanced HCC. Neighborhood factors were not associated with mortality or readmissions. Conclusion We observed that in addition to age and sex, Asian race, lower household income, lower education, and lower English proficiency were associated with increased risk of advanced HCC. These disparities likely reflect suboptimal screening programs and linkage to care among vulnerable populations. Further efforts are crucial to validate and address these concerning disparities.
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Affiliation(s)
- Xiaohan Ying
- NewYork Presbyterian / Weill Cornell Medical College, New York, NY, USA
| | - Yushan Pan
- Massachusetts General Hospital, Boston, MA, USA
| | - Russell Rosenblatt
- Weill Cornell Medicine, Division of Gastroenterology and Hepatology, New York, NY, USA
| | - Catherine Ng
- NewYork Presbyterian / Weill Cornell Medical College, New York, NY, USA
| | - Evan Sholle
- NewYork Presbyterian / Weill Cornell Medical College, New York, NY, USA
| | | | - Arun Jesudian
- Weill Cornell Medicine, Division of Gastroenterology and Hepatology, New York, NY, USA
| | - Brett E. Fortune
- Montefiore-Albert Einstein College of Medicine, Division of Hepatology, Bronx, NY, USA
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19
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Beal EW, Owen M, McNamara M, McAlearney AS, Tsung A. Patient-, Provider-, and System-Level Barriers to Surveillance for Hepatocellular Carcinoma in High-Risk Patients in the USA: a Scoping Review. J Gastrointest Cancer 2023; 54:332-356. [PMID: 35879510 DOI: 10.1007/s12029-022-00851-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/17/2022] [Indexed: 12/12/2022]
Abstract
PURPOSE Hepatocellular carcinoma has a dismal prognosis, except in patients diagnosed early who are candidates for potentially curative therapies. Most HCC cases develop in patients with chronic liver disease. Therefore, expert society guidelines recommend surveillance every 6 months with ultrasound with or without serum alpha-fetoprotein for high-risk patients. However, fewer than 20% of patients in the USA undergo appropriate surveillance. METHODS A systematic scoping review was performed with the objective of identifying barriers to screening among high-risk patients in the USA including mapping key concepts in the relevant literature, identifying the main sources and types of evidence available, and identifying gaps in the literature. A total of 43 studies published from 2007 to 2021 were included. Data were extracted and a conceptual framework was created. RESULTS Assessment of quantitative studies revealed poor surveillance rates, often below 50%. Three categories of barriers to surveillance were identified: patient-level, provider-level, and system-level barriers. Prevalent patient-level barriers included financial constraints, lack of awareness of surveillance recommendations, and scheduling difficulties. Common provider-level barriers were lack of provider awareness of guidelines for surveillance, difficulty accessing specialty resources, and time constraints in the clinic. System-level barriers included fewer clinic visits and rural/safety-net settings. Proposed interventions include improved patient/provider education, patient navigators, increased community/academic collaboration, and EMR-based reminders. CONCLUSION Based on these findings, there is a crucial need to implement and evaluate proposed interventions to improve HCC surveillance.
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Affiliation(s)
- Eliza W Beal
- The Ohio State University Comprehensive Cancer Center, Columbus, OH, 43210, USA.
- The Center for the Advancement of Team Science, Systems Thinking in Health Services and Implementation Science Research (CATALYST, The Ohio State University College of Medicine, AnalyticsColumbus, OH, 43210, USA.
| | - Mackenzie Owen
- The Ohio State University College of Medicine, Columbus, OH, 43210, USA
| | - Molly McNamara
- The Ohio State University College of Medicine, Columbus, OH, 43210, USA
| | - Ann Scheck McAlearney
- The Ohio State University Comprehensive Cancer Center, Columbus, OH, 43210, USA
- The Center for the Advancement of Team Science, Systems Thinking in Health Services and Implementation Science Research (CATALYST, The Ohio State University College of Medicine, AnalyticsColumbus, OH, 43210, USA
- The Department of Family and Community Medicine, The Ohio State University College of Medicine, Columbus, OH, 43210, USA
| | - Allan Tsung
- The Ohio State University Comprehensive Cancer Center, Columbus, OH, 43210, USA
- The Center for the Advancement of Team Science, Systems Thinking in Health Services and Implementation Science Research (CATALYST, The Ohio State University College of Medicine, AnalyticsColumbus, OH, 43210, USA
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20
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Rasic G, de Geus SWL, Papageorge MV, Woods AP, Ng SC, McAneny D, Tseng JF, Sachs TE. Disparities in the Receipt of Recommended Curative Treatment for Patients with Early-Stage Hepatocellular Carcinoma. World J Surg 2023; 47:1780-1789. [PMID: 36918443 DOI: 10.1007/s00268-023-06969-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/25/2022] [Indexed: 03/16/2023]
Abstract
BACKGROUND In early-stage hepatocellular carcinoma (HCC), the receipt of recommended care is critical for long-term survival. Unfortunately, not all patients decide to undergo therapy. We sought to identify factors associated with the decision to decline recommended intervention among patients with early-stage HCC. METHODS The National Cancer Database was queried for patients diagnosed with clinical stages I and II HCC (2004-2017). Cohorts were created based on the receipt or decline of recommended interventions-hepatectomy, liver transplantation, and ablation. Multivariable logistic regression identified predictors for declining intervention, and propensity score analysis was used to calculate the respective odds. Survival analysis was performed using the Kaplan-Meier method. RESULTS Of 20,863 patients, 856 (4.1%) declined intervention. Patients who were documented as having declined intervention were more often Black (vs. other: OR, 1.3; 95% CI, 1.1-1.6; p = 0.0038), had Medicaid or no insurance (vs. Private, Medicare, or other government insurance): OR, 1.9; 95% CI, 1.6-2.3; p < 0.0001), lived in a low-income area (vs. other: OR, 1.4; 95% CI, 1.2-1.7; p < 0.0001), and received treatment at a non-academic center (vs. academic: OR, 2.1; 95% CI, 1.9-2.5; p < 0.0001). Patients who declined recommended interventions had worse survival compared to those who received treatment (22.9 vs. 59.2 months; p < 0.0001, respectively). CONCLUSIONS Racial and socioeconomic disparities persist in the decision to undergo recommended treatment. Underutilization of treatment acts as a barrier to addressing racial and socioeconomic disparities in early-stage HCC outcomes.
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Affiliation(s)
- Gordana Rasic
- Department of Surgery, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA
| | - Susanna W L de Geus
- Department of Surgery, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA
| | - Marianna V Papageorge
- Department of Surgery, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA
| | - Alison P Woods
- Department of Surgery, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA.,Division of Surgical Oncology, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Sing Chau Ng
- Department of Surgery, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA
| | - David McAneny
- Department of Surgery, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA
| | - Jennifer F Tseng
- Department of Surgery, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA
| | - Teviah E Sachs
- Department of Surgery, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA. .,Department of Surgical Oncology, Boston Medical Center, 820 Harrison Avenue, FGH Building-Suite 5007, Boston, MA, 02118, USA.
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21
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Shi K, Li P, Zhang Q, Zhang Y, Bi Y, Zeng X, Wang X. Development of a nomogram to predict the risk of hepatocellular carcinoma in patients with hepatitis B-related cirrhosis on antivirals. Front Oncol 2023; 13:1128062. [PMID: 36874109 PMCID: PMC9978349 DOI: 10.3389/fonc.2023.1128062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Accepted: 02/06/2023] [Indexed: 02/18/2023] Open
Abstract
Objective Patients with compensated hepatitis B-related cirrhosis receiving antivirals are at the risk of hepatocellular carcinoma (HCC). This study aimed to develop and validate a nomogram for predicting the incidence of HCC in patients with hepatitis-B related cirrhosis. Design A total of 632 patients with compensated hepatitis-B related cirrhosis treated with entecavir or tenofovir between August 2010 and July 2018 were enrolled. Cox regression analysis was used to identify independent risk factors for HCC and a nomogram was developed using these factors. The area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analyses were used to evaluate the nomogram performance. The results were validated in an external cohort (n = 324). Results In the multivariate analysis, age per 10 years, neutrophil-lymphocyte ratio > 1.6, and platelet count < 86×109/L were independent predictors of HCC occurrence. A nomogram was developed to predict HCC risk using these three factors (ranging from 0 to 20). The nomogram showed better performance (AUC: 0.83) than that of the established models (all P < 0.05). The 3-year cumulative HCC incidences in the low- (scores < 4), medium- (4-10), and high-risk (> 10) subgroups were 0.7%, 4.3%, and 17.7%, respectively, in the derivation cohort, and 1.2%, 3.9%, and 17.8%, respectively, in the validation cohort. Conclusion The nomogram showed good discrimination and calibration in estimating HCC risk in patients with hepatitis-B related cirrhosis on antivirals. High-risk patients with a score > 10 points require close surveillance.
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Affiliation(s)
- Ke Shi
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ping Li
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, China
| | - Qun Zhang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yi Zhang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yufei Bi
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xuanwei Zeng
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xianbo Wang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
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22
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Jaffe A, Taddei TH, Giannini EG, Ilagan-Ying YC, Colombo M, Strazzabosco M. Holistic management of hepatocellular carcinoma: The hepatologist's comprehensive playbook. Liver Int 2022; 42:2607-2619. [PMID: 36161463 PMCID: PMC10878125 DOI: 10.1111/liv.15432] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 08/26/2022] [Accepted: 09/21/2022] [Indexed: 12/12/2022]
Abstract
Hepatocellular carcinoma (HCC) is a common complication in patients with chronic liver disease and leads to significant morbidity and mortality. Liver disease and liver cancer are preventable by mitigating and managing common risk factors, including chronic hepatitis B and C infection, alcohol use, diabetes, obesity and other components of the metabolic syndrome. The management of patients with HCC requires treatment of the malignancy and adequate control of the underlying liver disease, as preserving liver function is critical for successful cancer treatment and may have a relevant prognostic role independent of HCC management. Hepatologists are the ideal providers to guide the care of patients with HCC as they are trained to identify patients at risk, apply appropriate surveillance strategies, assess and improve residual liver function, evaluate candidacy for transplant, provide longitudinal care to optimize and preserve liver function during and after HCC treatment, survey for cancer recurrence and manage its risk factors, and prevent and treat decompensating events. We highlight the need for a team-based holistic approach to the patient with liver disease and HCC and identify necessary gaps in current care and knowledge.
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Affiliation(s)
- Ariel Jaffe
- Liver Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
- Smilow Cancer Hospital and Liver Cancer Program, New Haven, CT, USA
| | - Tamar H. Taddei
- Liver Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
| | - Edoardo G. Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Ysabel C. Ilagan-Ying
- Liver Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
| | | | - Mario Strazzabosco
- Liver Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
- Smilow Cancer Hospital and Liver Cancer Program, New Haven, CT, USA
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23
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Chang SS, Hu HY, Cheng FS, Chen YC, Yen YF, Huang N. Factors associated with nonadherence to surveillance for hepatocellular carcinoma among patients with hepatic C virus cirrhosis, 2000-2015. Medicine (Baltimore) 2022; 101:e31907. [PMID: 36451463 PMCID: PMC9704922 DOI: 10.1097/md.0000000000031907] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/04/2022] Open
Abstract
Hepatocellular carcinoma (HCC) surveillance can detect the early stage of tumors and lead to improved survival. Adherence to guideline-concordant HCC surveillance is crucial in at-risk populations, including patients with hepatic C virus (HCV) cirrhosis. This study was conducted to identify patient and provider factors associated with nonadherence to HCC surveillance in patients with HCV cirrhosis. Data were primarily obtained from the Taiwan National Health Insurance Research Database for the 2000 to 2015 period. Adult patients newly diagnosed as having HCV cirrhosis between 2003 and 2012 were enrolled. Each patient was followed up for 3 years and until the end of 2015. Annual HCC surveillance was defined as the uptake of an abdominal ultrasound and alpha-fetoprotein (AFP) test annually during the 3-years follow-up. Nonannual surveillance was defined as the lack of an annual abdominal ultrasound and AFP test during the same 3-years period. Multinomial logistic regression models were applied to determine factors influencing adherence or nonadherence to annual HCC surveillance. We included a total of 4641 patients with HCV cirrhosis for analysis. Of these patients, only 14% adhered to annual HCC surveillance. HCC surveillance improved in later years, compared with the earlier phases of the study period. Patients with HCV cirrhosis comorbid with coronary artery disease (CAD) or chronic obstructive pulmonary disease (COPD) or those with a relatively high number of comorbidities had a significantly higher likelihood of nonadherence. Patients who primarily received care from internists were significantly less likely to exhibit nonadherence to annual HCC surveillance compared with patients receiving care from physicians of other specialties. Patients who primarily received care from physicians practicing in larger hospitals were significantly less likely to exhibit nonadherence. HCC surveillance rates remain unacceptably low among high-risk patients, and our findings may be helpful in the development of effective interventions to increase HCC surveillance. The effective incorporation of HCC surveillance into routine visits for other chronic comorbidities, particularly for CAD or COPD, may be crucial for increasing HCC surveillance.
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Affiliation(s)
- Shen-Shong Chang
- Division of Gastroenterology
- Department of Internal Medicine; Taipei City Hospital Yang-Ming Branch
- Department of Medicine, School of Medicine
- Institute of Public Health and Department of Public Health
| | - Hsiao-Yun Hu
- Institute of Public Health and Department of Public Health
- Institute of Hospital and Health Care Administration; National Yang Ming Chiao Tung University
| | - Feng-Shiang Cheng
- Institute of Hospital and Health Care Administration; National Yang Ming Chiao Tung University
| | - Yu-Chin Chen
- Department of Education and Research; Taipei City Hospital
| | - Yung-Feng Yen
- Institute of Public Health and Department of Public Health
- Institute of Hospital and Health Care Administration; National Yang Ming Chiao Tung University
- Section of Infectious Diseases, Taipei City Hospital Yang-Ming Branch
- Department of Health Care Management, National Taipei University of Nursing and Health Sciences
| | - Nicole Huang
- Department of Education and Research; Taipei City Hospital
- * Correspondence: Nicole Huang, Institute of Hospital and Health Care Administration, School of Medicine, National Yang Ming Chiao Tung University, Room 201, The Medical Building II, No. 155, Section 2, Li-Nong Street, Taipei 112, Taiwan (e-mail: )
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24
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Papageorge MV, Sachs TE. ASO Author Reflections: Understanding How to Improve Surveillance in Hepatocellular Carcinoma. Ann Surg Oncol 2022; 29:8432-8433. [PMID: 36100835 DOI: 10.1245/s10434-022-12523-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Accepted: 08/24/2022] [Indexed: 11/18/2022]
Affiliation(s)
- Marianna V Papageorge
- Department of Surgery, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA
| | - Teviah E Sachs
- Department of Surgery, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA.
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25
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Papageorge MV, de Geus SWL, Woods AP, Ng SC, Lee S, McAneny D, Tseng JF, Kenzik KM, Sachs TE. Surveillance Patterns for Hepatocellular Carcinoma among Screening-Eligible Patients in the Medicare Population. Ann Surg Oncol 2022; 29:8424-8431. [PMID: 36057903 DOI: 10.1245/s10434-022-12360-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 07/14/2022] [Indexed: 12/19/2022]
Abstract
INTRODUCTION Routine screening plays a critical role in the diagnosis of hepatocellular carcinoma (HCC), but not all patients undergo consistent surveillance. This study aims to evaluate surveillance patterns and their association with diagnosis stage and survival among Medicare patients at risk for HCC. PATIENTS AND METHODS Patients with HCC and guideline-based screening eligibility who underwent imaging with ultrasound or abdominal magnetic resonance imaging (MRI) in the 2 years prior to diagnosis were identified from SEER-Medicare (2008-2015). Three surveillance cohorts were created: diagnostic (imaging only within 3 months prior), intermittent (imaging only once within 2 years prior, excluding diagnostic), and routine (at least two imaging encounters within 2 years prior, excluding diagnostic). Multivariable logistic regression was used to predict early-stage diagnosis (stage I-II), and 5-year survival was evaluated using the accelerated failure time method with Weibull distribution. RESULTS Among 2261 eligible patients, 26.1% were classified as diagnostic, 15.8% as intermittent, and 58.1% as routine surveillance. The median age was 74 years (IQR 70-78 years). The majority of patients had a preexisting cirrhosis diagnosis (81.5%). Routine and intermittent, compared with diagnostic, surveillance were predictive of early-stage disease (routine: OR 2.05, 95% CI 1.64-2.56; intermittent: OR 1.43, 95% CI 1.07-1.90). Patients who underwent routine surveillance had significantly lower risk of mortality (HR 0.84, 95% CI 0.75-0.94) compared with the diagnostic group. CONCLUSIONS A large proportion of screening-eligible patients do not undergo routine surveillance, which is associated with late-stage diagnosis and higher risk of mortality. These findings demonstrate the impact of timely and consistent healthcare access and can guide interventions for promoting surveillance among these patients.
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Affiliation(s)
- Marianna V Papageorge
- Department of Surgery, Boston Medical Center, Boston University School of Medical, Boston, MA, USA
| | - Susanna W L de Geus
- Department of Surgery, Boston Medical Center, Boston University School of Medical, Boston, MA, USA
| | - Alison P Woods
- Department of Surgery, Boston Medical Center, Boston University School of Medical, Boston, MA, USA.,Division of Surgical Oncology, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Sing Chau Ng
- Department of Surgery, Boston Medical Center, Boston University School of Medical, Boston, MA, USA
| | | | - David McAneny
- Department of Surgery, Boston Medical Center, Boston University School of Medical, Boston, MA, USA
| | - Jennifer F Tseng
- Department of Surgery, Boston Medical Center, Boston University School of Medical, Boston, MA, USA
| | - Kelly M Kenzik
- Department of Surgery, Boston Medical Center, Boston University School of Medical, Boston, MA, USA
| | - Teviah E Sachs
- Department of Surgery, Boston Medical Center, Boston University School of Medical, Boston, MA, USA.
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26
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Lee RM, Darby R, Medin CR, Haser GC, Mason MC, Miller LS, Staley CA, Maithel SK, Russell MC. Implementation of a Hepatocellular Carcinoma Screening Program for At-risk Patients Safety-Net Hospital: A Model for National Dissemination. Ann Surg 2022; 276:545-553. [PMID: 35837969 PMCID: PMC9675906 DOI: 10.1097/sla.0000000000005582] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE This study aimed to enhance hepatocellular carcinoma (HCC) screening to achieve earlier diagnosis of patients with hepatitis C (HCV) cirrhosis in our Safety-Net population. BACKGROUND Adherence to HCC screening guidelines at Safety-Net hospitals is poor. Only 23% of patients with HCC at our health system had a screening exam within 1-year of diagnosis and 46% presented with stage IV disease. HCV-induced cirrhosis remains the most common etiology of HCC (75%) in our patients. METHODS In the setting of an established HCV treatment clinic, an HCC screening quality improvement initiative was initiated for patients with stage 3 fibrosis or cirrhosis by transient elastography. The program consisted of semiannual imaging. Navigators scheduled imaging appointments and tracked compliance. RESULTS From April 2018 to April 2021, 318 patients were enrolled (mean age 61 years, 81% Black race, 38% uninsured). Adherence to screening was higher than previously reported: 94%, 75%, and 74% of patients completed their first, second, and third imaging tests. Twenty-two patients (7%) were diagnosed with HCC; 55% stage I and 14% stage IV. All patients were referred and 13 (59%) received treatment. Median time to receipt of treatment was 77 days (range, 32-282). Median overall survival for treated patients was 32 months. CONCLUSIONS Implementation of an HCC screening program at a safety-net hospital is feasible and facilitated earlier diagnosis in this study. Patient navigation and tracking completion of imaging tests were key components of the program's success. Next steps include expanding the program to additional at-risk populations.
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Affiliation(s)
- Rachel M Lee
- Department of Surgery, Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA
| | - Rapheisha Darby
- Grady Liver Clinic, Primary Care Centers, Grady Memorial Hospital, Atlanta, GA
| | - Caroline R Medin
- Department of Surgery, Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA
| | - Grace C Haser
- Department of Medicine, Division of General Internal Medicine, Emory University, Atlanta, GA
| | - Meredith C Mason
- Department of Surgery, Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA
| | - Lesley S Miller
- Department of Medicine, Division of General Internal Medicine, Emory University, Atlanta, GA
| | - Charles A Staley
- Department of Surgery, Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA
| | - Shishir K Maithel
- Department of Surgery, Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA
| | - Maria C Russell
- Department of Surgery, Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA
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27
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Choi J, Tayob N, Lim YS. Detecting Early Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Using Longitudinal α-Fetoprotein Screening. Clin Gastroenterol Hepatol 2022; 21:1590-1597. [PMID: 36031091 PMCID: PMC9968818 DOI: 10.1016/j.cgh.2022.08.018] [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: 05/04/2022] [Revised: 07/28/2022] [Accepted: 08/17/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS This study aimed to evaluate the parametric empirical Bayes (PEB) longitudinal α-fetoprotein (AFP) screening algorithm performance in patients with hepatitis B compared with AFP surveillance with a fixed threshold. METHODS The serum AFP of 588 patients was measured. Patients were screened at least once every 6 months with AFP and ultrasound or computed tomography/magnetic resonance imaging. Age, aspartate aminotransferase level, alanine aminotransferase level, platelet count, total bilirubin, prothrombin time, and hepatitis B virus DNA level were adjusted in the PEB algorithm. All variables were abstracted at the time of hepatocellular carcinoma (HCC) diagnosis for cases or last follow-up for controls and at months -6, -12, -18, -24, -30, -36, -42, -48, and -54, up to month -60. RESULTS Overall, 62 (10.5%) HCC cases developed during a median follow-up of 52.7 months. Moreover, 55 (88.7%) cases were detected at Barcelona Clinic Liver Cancer stage 0 or A. The area under the receiver-operating characteristic curve of the patient-level true positive rate against the screening-level false positive rate was significantly higher in the PEB algorithm than that in AFP alone (area under the receiver-operating characteristic curve: 0.94 vs 0.86; P < .0005). At 80% specificity, the PEB algorithm significantly improved the patient-level true positive rate within 2 years prior to HCC diagnosis compared with AFP alone (80.6% vs 67.7%, respectively; P = .0485; adjusted P = .1663). The PEB algorithm more effectively enabled first positive screening. CONCLUSIONS The longitudinal assessment of AFP by the PEB algorithm improved HCC screening performance compared to AFP alone in patients with hepatitis B. This algorithm may improve HCC screening without additional cost or inconvenience to patients.
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Affiliation(s)
- Jonggi Choi
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
| | - Nabihah Tayob
- Department of Data Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts
| | - Young-Suk Lim
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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28
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Papageorge MV, Woods AP, de Geus SWL, Ng SC, Paasche-Orlow MK, Segev D, McAneny D, Kenzik KM, Sachs TE, Tseng JF. Beyond insurance status: the impact of Medicaid expansion on the diagnosis of Hepatocellular Carcinoma. HPB (Oxford) 2022; 24:1271-1279. [PMID: 35042672 DOI: 10.1016/j.hpb.2021.12.020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2021] [Revised: 12/20/2021] [Accepted: 12/29/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Medicaid expansion has led to earlier stage diagnoses in several cancers but has not been studied in hepatocellular carcinoma (HCC), a disease with complex risk factors. We examined the effect of Medicaid expansion on the diagnosis of HCC and associations with county-level social vulnerability. METHODS Patients with HCC <65 years of age were identified from the SEER database (2010-2016). County-level social vulnerability factors were obtained from the CDC SVI and BRFSS. A Difference-in-Difference analysis evaluated change in early-stage diagnoses (stage I-II) between expansion and non-expansion states. A Difference-in-Difference-in-Difference analysis evaluated expansion impact among counties with higher proportions of social vulnerability. RESULTS Of 19,751 patients identified, 81.5% were in expansion states. Uninsured status decreased in expansion states (6.3%-2.4%, p < 0.0001) and remained unchanged in non-expansion states (12.7%-14.8%, p = 0.43). There was no significant difference in the incidence of early-stage diagnoses between expansion states and non-expansion states. Results were consistent when accounting for social vulnerability. CONCLUSION Medicaid expansion was not associated with earlier stage diagnoses in patients with HCC, including those with higher social vulnerability. Unlike other cancers, expanded access did not translate into higher utilization of care in HCC, suggesting barriers on a multitude of levels.
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Affiliation(s)
- Marianna V Papageorge
- Department of Surgery, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA
| | - Alison P Woods
- Department of Surgery, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Susanna W L de Geus
- Department of Surgery, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA
| | - Sing Chau Ng
- Department of Surgery, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA
| | - Michael K Paasche-Orlow
- Department of Medicine, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA
| | - Dorry Segev
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - David McAneny
- Department of Surgery, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA
| | - Kelly M Kenzik
- Department of Surgery, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA; Division of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Teviah E Sachs
- Department of Surgery, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA
| | - Jennifer F Tseng
- Department of Surgery, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA.
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Kim AK, Hamilton JP, Lin SY, Chang TT, Hann HW, Hu CT, Lou Y, Lin YJ, Gade TP, Park G, Luu H, Lee TJ, Wang J, Chen D, Goggins MG, Jain S, Song W, Su YH. Urine DNA biomarkers for hepatocellular carcinoma screening. Br J Cancer 2022; 126:1432-1438. [PMID: 35046521 PMCID: PMC9091244 DOI: 10.1038/s41416-022-01706-9] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 12/20/2021] [Accepted: 01/07/2022] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) occurs in a well-defined high-risk patient population, but better screening tests are needed to improve sensitivity and efficacy. Therefore, we investigated the use of urine circulating tumour DNA (ctDNA) as a screening test. METHODS Candidate markers in urine were selected from HCC and controls. We then enrolled 609 patients from five medical centres to test the selected urine panel. A two-stage model was developed to combine AFP and urine panel as a screening test. RESULTS Mutated TP53, and methylated RASSF1a, and GSTP1 were selected as the urine panel markers. Serum AFP outperformed the urine panel among all cases of HCC, but the urine panel identified 49% of HCC cases with low AFP < 20 ng/ml. Using the two-stage model, the combined AFP and urine panel identified 148 of the 186 HCC cases (79.6% sensitivity at 90% specificity), which was 30% more than the cases detected with serum AFP alone. It also increased early-stage HCC detection from 62% to 92% (BCLC stage 0), and 40% to 77% (BCLC stage A). CONCLUSION Urine ctDNA has promising diagnostic utility in patients in HCC, especially in those with low AFP and can be used as a potential non-invasive HCC screening test.
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Affiliation(s)
- Amy K Kim
- Division of Gastroenterology and Hepatology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - James P Hamilton
- Division of Gastroenterology and Hepatology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | | | - Ting-Tsung Chang
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Hie-Won Hann
- Department of Medicine, Division of Gastroenterology and Hepatology, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - Chi-Tan Hu
- Division of Gastroenterology, Department of Internal Medicine, Hualien Tzu-Chi Hospital, Buddhist Tzu-Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
| | - Yue Lou
- The Baruch S. Blumberg Institute, Doylestown, PA, USA
| | - Yih-Jyh Lin
- Department of Surgery, National Cheng Kung University Medical College and Hospital, Tainan, Taiwan, Republic of China
| | - Terence P Gade
- Department of Radiology, University of Pennsylvania College of Medicine, Philadelphia, PA, USA
| | - Grace Park
- Department of Medicine, Division of Gastroenterology and Hepatology, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - Harry Luu
- Division of Gastroenterology and Hepatology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Tai-Jung Lee
- The Baruch S. Blumberg Institute, Doylestown, PA, USA
| | | | - Dion Chen
- ClinPharma Consulting, Inc, Phoenixville, PA, USA
| | - Michael G Goggins
- Division of Gastroenterology and Hepatology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
- Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, MD, USA
| | | | - Wei Song
- JBS Science, Inc., Doylestown, PA, USA
| | - Ying-Hsiu Su
- The Baruch S. Blumberg Institute, Doylestown, PA, USA.
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30
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Tan J, Tang X, He Y, Xu X, Qiu D, Chen J, Zhang Q, Zhang L. In-patient Expenditure Between 2012 and 2020 Concerning Patients With Liver Cirrhosis in Chongqing: A Hospital-Based Multicenter Retrospective Study. Front Public Health 2022; 10:780704. [PMID: 35350474 PMCID: PMC8957842 DOI: 10.3389/fpubh.2022.780704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 02/11/2022] [Indexed: 11/13/2022] Open
Abstract
Background Liver cirrhosis is a major global health and economic challenge, placing a heavy economic burden on patients, families, and society. This study aimed to investigate medical expenditure trends in patients with liver cirrhosis and assess the drivers for such medical expenditure among patients with liver cirrhosis. Methods Medical expenditure data concerning patients with liver cirrhosis was collected in six tertiary hospitals in Chongqing, China, from 2012 to 2020. Trends in medical expenses over time and trends according to subgroups were described, and medical expenditure compositions were analyzed. A multiple linear regression model was constructed to evaluate the factors influencing medical expenditure. All expenditure data were reported in Chinese Yuan (CNY), based on the 2020 value, and adjusted using the year-specific health care consumer price index for Chongqing. Results Medical expenditure for 7,095 patients was assessed. The average medical expenditure per patient was 16,177 CNY. An upward trend in medical expenditure was observed in almost all patient subgroups. Drug expenses were the largest contributor to medical expenditure in 2020. A multiple linear regression model showed that insurance type, sex, age at diagnosis, marital status, length of stay, smoking status, drinking status, number of complications, autoimmune liver disease, and the age-adjusted Charlson comorbidity index score were significantly related to medical expenditure. Conclusion Conservative estimates suggest that the medical expenditure of patients with liver cirrhosis increased significantly from 2012 to 2020. Therefore, it is necessary to formulate targeted measures to reduce the personal burden on patients with liver cirrhosis.
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Affiliation(s)
- Juntao Tan
- Medical Records and Statistics Room, People's Hospital of Chongqing Banan District, Chongqing, China
| | - Xuewen Tang
- Department of Cardiology, People's Hospital of Chongqing Banan District, Chongqing, China
| | - Yuxin He
- Department of Medical Administration, People's Hospital of Chongqing Banan District, Chongqing, China
| | - Xiaomei Xu
- Department of Gastroenterology, The Fifth People's Hospital of Chengdu, Chengdu, China.,Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Daoping Qiu
- Medical Records and Statistics Room, People's Hospital of Chongqing Banan District, Chongqing, China
| | - Jianfei Chen
- Department of Cardiology, People's Hospital of Chongqing Banan District, Chongqing, China
| | - Qinghua Zhang
- Department of Science and Education, People's Hospital of Chongqing Banan District, Chongqing, China
| | - Lingqin Zhang
- Department of Biomedical Equipment, People's Hospital of Chongqing Bishan District, Chongqing, China
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31
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Perumalswami PV, Wyatt B, Bowman CA, Patel K, Mageras A, Lewis SC, Branch AD. Hepatocellular carcinoma surveillance, incidence, and tumor doubling times in patients cured of hepatitis C. Cancer Med 2022; 11:1995-2005. [PMID: 35261196 PMCID: PMC9089228 DOI: 10.1002/cam4.4508] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Revised: 12/02/2021] [Accepted: 12/03/2021] [Indexed: 11/24/2022] Open
Abstract
Background Hepatocellular carcinoma (HCC) incidence and mortality vary by race/ethnicity and both are higher in Black patients than in Whites. For HCC surveillance, all cirrhotic patients are advised to undergo lifelong twice‐annual abdominal imaging. We investigated factors associated with surveillance and HCC incidence in a diverse HCC risk group, cirrhotic patients recently cured of hepatitis C virus (HCV) infection. Methods In this observational cohort study, all participants (n = 357) had advanced fibrosis/cirrhosis and were cured of HCV with antiviral treatment. None had Liver Imaging Reporting and Data System (LI‐RADS) 2–5 lesions prior to HCV cure. Ultrasound, computed tomography, and/or magnetic resonance imaging were used for surveillance. Results At a median follow‐up of 40 months [interquartile range (IQR) = 28–48], the median percentage of time up‐to‐date with surveillance was 49% (IQR) = 30%–71%. The likelihood of receiving a first surveillance examination was not significantly associated with race/ethnicity, but was higher for patients with more advanced cirrhosis, for example, bilirubin [odds ratio (OR) = 3.8/mg/dL, p = 0.002], private insurance (OR = 3.4, p = 0.006), and women (OR = 2.3, p = 0.008). The likelihood of receiving two or three examinations was significantly lower for non‐Hispanic Blacks and Hispanics versus non‐Hispanic Whites (OR = 0.39, and OR = 0.40, respectively, p < 0.005 for both) and for patients with higher platelet counts (OR = 0.99/10,000 cells/µl, p = 0.01), but higher for patients with private insurance (OR = 2.8, p < 0.001). Incident HCC was associated with higher bilirubin (OR = 1.7, p = 0.02) and lower lymphocyte counts (OR = 0.16, p = 0.01). Conclusions Contrary to best practices, HCC surveillance was associated with sociodemographic factors (insurance status and race/ethnicity) among patients cured of HCV. Guideline‐concordant surveillance is needed to address healthcare disparities.
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Affiliation(s)
- Ponni V Perumalswami
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Brooke Wyatt
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Chip A Bowman
- Division of Hospital Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Krupa Patel
- Division of Hospital Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Anna Mageras
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Sara C Lewis
- Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Andrea D Branch
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA
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32
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Fazeli S, Covarrubias Y, Bassirian S, Cuevas J, Fowler K, Vodkin I, Kono Y, Marks R, Loomba R, Taouli B, Sirlin C, Carlos R. Eliciting Patient Preferences for Hepatocellular Carcinoma Screening: A Choice-Based Conjoint Analysis. J Am Coll Radiol 2022; 19:502-512. [DOI: 10.1016/j.jacr.2022.01.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Revised: 01/04/2022] [Accepted: 01/04/2022] [Indexed: 12/22/2022]
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Jo AJ, Choi WM, Kim HJ, Choi SH, Han S, Ko MJ, Lim YS. A risk scoring system to predict clinical events in chronic hepatitis B virus infection: A nationwide cohort study. J Viral Hepat 2022; 29:115-123. [PMID: 34762757 DOI: 10.1111/jvh.13631] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Revised: 10/19/2021] [Accepted: 11/02/2021] [Indexed: 02/06/2023]
Abstract
Many patients with chronic hepatitis B do not receive adequate follow-up. This study aimed to develop a risk score to predict clinical events in patients with chronic hepatitis B virus (HBV) infection at the population level for identifying patients at high risk to warrant regular follow-up. This study analysed population-based data from the nationwide claims database of South Korea obtained between 2005 and 2015. We identified 507,239 non-cirrhotic patients with chronic HBV infection who are not under antiviral treatment. A risk score for predicting clinical events (hepatocellular carcinoma, death or liver transplantation) was developed based on multivariable Cox proportional hazard model in a development cohort (n = 401,745) and validated in a validation cohort (n = 105,494). The cumulative incidence rates of clinical events at 5 years were 2.56% and 2.44% in the development and validation cohorts, respectively. Clinical events in asymptomatic patients with chronic HBV infection (CAP-B) score ranging from 0 to 7.5 points based on age, sex, socioeconomic status, chronic hepatitis C co-infection, diabetes mellitus, statin or antiplatelet exposure, smoking, alcohol consumption, alanine aminotransferase and gamma-glutamyltransferase had good discriminatory accuracy in both the development and validation cohorts (c-indices for 3-, 5- and 10-year risk prediction: all 0.786). The predicted and observed probabilities of clinical events were calibrated in both cohorts. A score of >3.5 points identified subjects at distinctly high risk. The CAP-B score using easily accessible variables can predict clinical events and may allow selection of patients with chronic HBV infection for priority of regular follow-up.
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Affiliation(s)
- Ae Jeong Jo
- Division for Healthcare Technology Assessment Research, National Evidence-Based Healthcare Collaborating Agency, Seoul, Republic of Korea
| | - Won-Mook Choi
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Hyo Jeong Kim
- Division for Healthcare Technology Assessment Research, National Evidence-Based Healthcare Collaborating Agency, Seoul, Republic of Korea
| | - So Hyun Choi
- Division for Healthcare Technology Assessment Research, National Evidence-Based Healthcare Collaborating Agency, Seoul, Republic of Korea.,Department of Statistics, Kyungpook National University, Daegu, Republic of Korea
| | - Seungbong Han
- Department of Biostatistics, Korea University College of Medicine, Seoul, Republic of Korea
| | - Min Jung Ko
- Division for Healthcare Technology Assessment Research, National Evidence-Based Healthcare Collaborating Agency, Seoul, Republic of Korea
| | - Young-Suk Lim
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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34
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Ohikere K, Chitnis AS, Hahambis TA, Singal A, Wong RJ. Ethnic Minorities and Low Socioeconomic Status Patients With Chronic Liver Disease Are at Greatest Risk of Being Uninsured. Gastroenterology Res 2022; 14:313-323. [PMID: 35059065 PMCID: PMC8734498 DOI: 10.14740/gr1439] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Accepted: 07/15/2021] [Indexed: 12/16/2022] Open
Abstract
Background Chronic liver disease (CLD) predominantly affects ethnic minorities and socially vulnerable populations, who have high prevalence of risk factors (e.g., suboptimal insurance coverage) predisposing to healthcare disparities. We evaluate prevalence and predictors of uninsured status among CLD adults, and secondarily, how this affects documented immunity or vaccination for hepatitis A virus (HAV) and hepatitis B virus (HBV). Methods Using 2011 - 2018 National Health and Nutrition Examination Survey data, self-reported insurance status was determined among adults with CLD. Prevalence of uninsured status was stratified by patient characteristics and evaluated using multivariable logistic regression models. Prevalence of self-reported completion of vaccination as well as laboratory value-based documented immunity to HAV and HBV was stratified by insurance status. Results Overall, 19.0% of adults with CLD reported having no insurance, which was highest among individuals of Hispanic ethnicity (33.5%), less than high school education (33.7%), and below poverty status (35.3%). On multivariable analyses, significantly lower odds of having any insurance coverage was observed in men, Hispanics, and individuals with lower education and lower household income. Prevalence of documented immunity or vaccination for HAV was low across all insurance categories, ranging from 46.5% to 54.0%. Prevalence of documented immunity or vaccination for HBV was similarly low across all insurance categories, ranging from 24.3% to 40.8%. Conclusion Prevalence of uninsured status among CLD was more than twice the US adult population, and lack of insurance particularly impacted Hispanics and individuals with low education and low household income. Low prevalence of documented immunity or vaccination for HAV and HBV across all insurance categories is concerning.
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Affiliation(s)
- Kabiru Ohikere
- Division of Research, Kaiser Permanente, Oakland, CA, USA
| | - Amit S Chitnis
- Tuberculosis Section, Division of Communicable Disease Control and Prevention, Alameda County Public Health Department, San Leandro, CA, USA
| | | | - Ashwani Singal
- Department of Medicine, University of South Dakota Sanford School of Medicine, Sioux Falls, SD, USA.,Division of Transplant Hepatology, Avera Transplant Institute, Sioux Falls, SD, USA
| | - Robert J Wong
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA.,Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA, USA
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35
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Khalil A, ElSheashaey A, Abdelsameea E, Obada M, Bayomy F.F. M, El-Said H. Value of Bile Acids in Diagnosing Hepatitis C Virus-Induced Liver Cirrhosis and Hepatocellular Carcinoma. Br J Biomed Sci 2022; 79:10191. [PMID: 35996509 PMCID: PMC8915635 DOI: 10.3389/bjbs.2021.10191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 12/02/2021] [Indexed: 11/13/2022]
Abstract
Background: Metabonomic studies have related bile acids to hepatic impairment, but their role in predicting hepatocellular carcinoma still unclear. The study aimed to examine the feasibility of bile acids in distinguishing hepatocellular carcinoma from post hepatitis C virus-induced liver cirrhosis.Methods: An ultra-performance liquid chromatography coupled with mass spectrometry measured 14 bile acids in patients with noncirrhotic post hepatitis C virus disease (n = 50), cirrhotic post hepatitis C virus disease (n = 50), hepatocellular carcinoma (n = 50), and control group (n = 50).Results: The spectrum of liver disease was associated with a significant increase in many conjugated bile acids. The fold changes in many bile acid concentrations showed a linear trend with hepatocellular carcinoma > cirrhotic disease > noncirrhotic disease > healthy controls (p < 0.05). Receiver operating characteristic curve analysis revealed five conjugated acids TCA, GCA, GUDCA, TCDCA, GCDCA, that discriminated hepatocellular carcinoma from noncirrhotic liver patients (AUC = 0.85–0.96) with a weaker potential to distinguish it from chronic liver cirrhosis (AUC = 0.41–0.64).Conclusion: Serum bile acids are associated primarily with liver cirrhosis with little value in predicting the progress of cirrhotic disease to hepatocellular carcinoma.
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Affiliation(s)
- Ashraf Khalil
- Department of Biochemistry and Molecular Diagnostics, National Liver Institute, Menoufia University, Shibin el Kom, Egypt
- *Correspondence: Ashraf Khalil,
| | - Azza ElSheashaey
- Department of Biochemistry and Molecular Diagnostics, National Liver Institute, Menoufia University, Shibin el Kom, Egypt
- Department of Zoology, Faculty of Science, Menoufia University, Shibin el Kom, Egypt
| | - Eman Abdelsameea
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shibin el Kom, Egypt
| | - Manar Obada
- Department of Biochemistry and Molecular Diagnostics, National Liver Institute, Menoufia University, Shibin el Kom, Egypt
| | - Mohamed Bayomy F.F.
- Department of Biochemistry and Molecular Diagnostics, National Liver Institute, Menoufia University, Shibin el Kom, Egypt
- Department of Zoology, Faculty of Science, Menoufia University, Shibin el Kom, Egypt
| | - Hala El-Said
- Department of Biochemistry and Molecular Diagnostics, National Liver Institute, Menoufia University, Shibin el Kom, Egypt
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Park HJ, Seo N, Kim SY. Current Landscape and Future Perspectives of Abbreviated MRI for Hepatocellular Carcinoma Surveillance. Korean J Radiol 2022; 23:598-614. [PMID: 35434979 PMCID: PMC9174497 DOI: 10.3348/kjr.2021.0896] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 01/18/2022] [Accepted: 02/10/2022] [Indexed: 11/15/2022] Open
Abstract
While ultrasound (US) is considered an important tool for hepatocellular carcinoma (HCC) surveillance, it has limited sensitivity for detecting early-stage HCC. Abbreviated MRI (AMRI) has recently gained popularity owing to better sensitivity in its detection of early-stage HCC than US, while also minimizing the time and cost in comparison to complete contrast-enhanced MRI, as AMRI includes only a few essential sequences tailored for detecting HCC. Currently, three AMRI protocols exist, namely gadoxetic acid-enhanced hepatobiliary-phase AMRI, dynamic contrast-enhanced AMRI, and non-enhanced AMRI. In this study, we discussed the rationale and technical details of AMRI techniques for achieving optimal surveillance performance. The strengths, weaknesses, and current issues of each AMRI protocol were also elucidated. Moreover, we scrutinized previously performed AMRI studies regarding clinical and technical factors. Reporting and recall strategies were discussed while considering the differences in AMRI protocols. A risk-stratified approach for the target population should be taken to maximize the benefits of AMRI and the cost-effectiveness should be considered. In the era of multiple HCC surveillance tools, patients need to be fully informed about their choices for better adherence to a surveillance program.
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Affiliation(s)
- Hyo Jung Park
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Nieun Seo
- Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - So Yeon Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
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37
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Carr BI, Bag HG, Ince V, Ogut Z, Tuncer A, Akbulut S, Ersan V, Usta S, Isik B, Yilmaz S. A simple 2-parameter blood test alert for the presence of small hepatocellular carcinomas. CLINICAL PRACTICE (LONDON, ENGLAND) 2021; 18:1804-1809. [PMID: 34966540 PMCID: PMC8714058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 09/28/2022]
Abstract
Objectives The majority of HCCs present at an advanced stage in which potentially curative therapies cannot be used. Surveillance ultrasound has been found to increase the numbers of patients diagnosed with small tumors, but it is often not used. We aimed to try to identify widely-available and cheap potential serum markers for use in patients at risk for HCC. Material and Methods A comparison was made of the complete blood count and liver function tests in a group of patients (n=114) with proven small HCCs (≤ 2 cm) and patients without HCC (n=506), all of whom were treated by liver transplantation in our Liver Transplantation Institute. Results Significant differences were found for blood levels of WBC, lymphocytes, total bilirubin and transaminases. Several 2-parameter combinations were assessed, but only the combination of total bilirubin and lymphocytes was found to be significantly different between patients with small HCCs and no HCC. Multivariate regression analysis showed significance only for total bilirubin levels and lymphocyte counts. The results were confirmed using a separate small cohort of non-transplant patients. Conclusion The combination of elevated levels of total bilirubin and lymphocyte counts holds promise for identification of patients with chronic liver disease who are at risk for HCC.
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Affiliation(s)
- Brian I Carr
- Liver Transplant Institute, Inonu University Faculty of Medicine, Malatya, Turkey
| | - Harika Gozukara Bag
- Department of Biostatistics, Inonu University Faculty of Medicine, Malatya, Turkey
| | - Volkan Ince
- Liver Transplant Institute, Inonu University Faculty of Medicine, Malatya, Turkey.,Department of Surgery, Inonu University Faculty of Medicine, Malatya, Turkey
| | - Zeki Ogut
- Department of Surgery, Inonu University Faculty of Medicine, Malatya, Turkey
| | - Adem Tuncer
- Department of Surgery, Inonu University Faculty of Medicine, Malatya, Turkey
| | - Sami Akbulut
- Department of Surgery, Inonu University Faculty of Medicine, Malatya, Turkey
| | - Veysel Ersan
- Liver Transplant Institute, Inonu University Faculty of Medicine, Malatya, Turkey.,Department of Surgery, Inonu University Faculty of Medicine, Malatya, Turkey
| | - Sertac Usta
- Liver Transplant Institute, Inonu University Faculty of Medicine, Malatya, Turkey.,Department of Surgery, Inonu University Faculty of Medicine, Malatya, Turkey
| | - Burak Isik
- Liver Transplant Institute, Inonu University Faculty of Medicine, Malatya, Turkey.,Department of Surgery, Inonu University Faculty of Medicine, Malatya, Turkey
| | - Sezai Yilmaz
- Liver Transplant Institute, Inonu University Faculty of Medicine, Malatya, Turkey.,Department of Surgery, Inonu University Faculty of Medicine, Malatya, Turkey
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38
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Carr BI, Bag HG, Ince V, Akbulut S, Ersan V, Usta S, Isik B, Ogut Z, Tuncer A, Yilmaz S. A Combination of Blood Lymphocytes and AST Levels Distinguishes Patients with Small Hepatocellular Carcinomas from Non-cancer Patients. J Gastrointest Cancer 2021; 52:1211-1216. [PMID: 34762264 PMCID: PMC8799503 DOI: 10.1007/s12029-021-00740-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/21/2021] [Indexed: 02/07/2023]
Abstract
PURPOSE HCC patients typically present at an advanced tumor stage, in which surgical therapies cannot be used. Screening ultrasound exams can increase the numbers of patients diagnosed with small tumors, but are often not used in patients at risk for HCC. We evaluated clinically available and cheap potential blood tests as biomarkers for screening patients at risk for HCC. METHODS A comparison was made of commonly used blood count and liver function parameters in a group of patients (n = 101) with small HCCs (≤ 3 cm) or without HCC (n = 275), who presented for liver transplantation in our institute. RESULTS Significant differences were found for blood lymphocytes and AST levels. This 2-parameter combination was found to be significantly different between patients with small HCCs versus no HCC. Using the combination of lymphocytes and AST levels to dichotomize the HCC patients, only blood levels of alpha-fetoprotein among the tumor characteristics were found to be significantly different among the 2 HCC groups, as well as levels of blood total bilirubin, ALKP, and PLR ratio. The results were confirmed using a separate smaller cohort of non-transplanted small size HCC patients. CONCLUSION The combination of elevated blood levels of lymphocyte counts and AST levels holds promise for screening of patients with chronic liver disease who are at risk for HCC.
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Affiliation(s)
- Brian I Carr
- Liver Transplant Institute, Faculty of Medicine, Inonu University, Bulgurlu Mah, Elazig Yolu 15 km, 44280, Malatya, Turkey.
| | - Harika Gozukara Bag
- Department of Biostatistics, Faculty of Medicine, Inonu University, 44280, Malatya, Turkey
| | - Volkan Ince
- Liver Transplant Institute, Faculty of Medicine, Inonu University, Bulgurlu Mah, Elazig Yolu 15 km, 44280, Malatya, Turkey
- Department of Surgery, Faculty of Medicine, Inonu University, 44280, Malatya, Turkey
| | - Sami Akbulut
- Liver Transplant Institute, Faculty of Medicine, Inonu University, Bulgurlu Mah, Elazig Yolu 15 km, 44280, Malatya, Turkey
- Department of Surgery, Faculty of Medicine, Inonu University, 44280, Malatya, Turkey
| | - Veysel Ersan
- Liver Transplant Institute, Faculty of Medicine, Inonu University, Bulgurlu Mah, Elazig Yolu 15 km, 44280, Malatya, Turkey
- Department of Surgery, Faculty of Medicine, Inonu University, 44280, Malatya, Turkey
| | - Sertac Usta
- Liver Transplant Institute, Faculty of Medicine, Inonu University, Bulgurlu Mah, Elazig Yolu 15 km, 44280, Malatya, Turkey
- Department of Surgery, Faculty of Medicine, Inonu University, 44280, Malatya, Turkey
| | - Burak Isik
- Liver Transplant Institute, Faculty of Medicine, Inonu University, Bulgurlu Mah, Elazig Yolu 15 km, 44280, Malatya, Turkey
- Department of Surgery, Faculty of Medicine, Inonu University, 44280, Malatya, Turkey
| | - Zeki Ogut
- Department of Surgery, Faculty of Medicine, Inonu University, 44280, Malatya, Turkey
| | - Adem Tuncer
- Department of Surgery, Faculty of Medicine, Inonu University, 44280, Malatya, Turkey
| | - Sezai Yilmaz
- Liver Transplant Institute, Faculty of Medicine, Inonu University, Bulgurlu Mah, Elazig Yolu 15 km, 44280, Malatya, Turkey
- Department of Surgery, Faculty of Medicine, Inonu University, 44280, Malatya, Turkey
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Khalil A, Elsheashaey A, Abdelsameea E, Obada M, Mohamed Bayomy FF, El-Said H. Role of bile acids in the prediction of hepatocellular carcinoma in HCV-induced liver cirrhosis. EGYPTIAN LIVER JOURNAL 2021. [DOI: 10.1186/s43066-021-00142-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Bile acids are essential organic molecules synthesized from cholesterol in the liver and regarded as indicators of hepatobiliary impairment; however, their role in the pathogenesis of hepatocellular carcinoma (HCC) is still unclear. The study aimed to examine the feasibility of bile acids in distinguishing HCC from post hepatitis C virus liver cirrhosis. A UPLC/MS was used to measure 14 bile acids in patients with noncirrhotic HCV disease (n = 50), cirrhotic HCV disease (n = 50), hepatocellular carcinoma (n = 50), and control group (n = 50).
Results
The progression of liver cirrhosis to HCC was associated with a significant increase in serum bile acids compared to the normal or the noncirrhotic HCV disease (p < 0.05). The fold changes in bile acids concentrations showed a trend that HCC > cirrhotic HCV disease > noncirrhotic HCV disease. Four conjugated acids GCA, GCDCA, GUDCA, and TCDCA steadily increased across the different groups. ROC curves analysis revealed that these bile acids discriminated noncirrhotic liver patients from HCC (AUC 0.850–0.963), with a weaker potential to distinguish chronic liver cirrhosis from HCC (AUC 0.414–0.638).
Conclusion
The level of serum bile acid was associated primarily with liver cirrhosis, with little value in predicting the progress of chronic liver cirrhotic disease into hepatocellular carcinoma.
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Huang DQ, Hoang JK, Leong J, Riveiro-Barciela M, Maeda M, Yang JD, Accarino EV, Thin K, Trinh L, Cheung RC, Roberts LR, Buti M, Schwartz M, Nguyen MH. Differential characteristics and outcomes of Asian and non-Asian patients with HBV-related hepatocellular carcinoma. Liver Int 2021; 41:1922-1932. [PMID: 33713386 DOI: 10.1111/liv.14877] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 02/16/2021] [Accepted: 03/07/2021] [Indexed: 12/25/2022]
Abstract
BACKGROUND & AIMS The epidemiology of hepatitis B virus (HBV) infection differs between Asians and non-Asians, but little is known regarding the effect of ethnicity on outcomes of HBV-related hepatocellular carcinoma (HCC). We aim to characterize the presentation and survival outcomes in Asian and non-Asian patients with HBV-related HCC. METHODS We analyzed the baseline characteristics and long-term survival of 613 Asian and 410 non-Asian patients with HBV-related HCC from three US and one Spanish centre. RESULTS Overall, non-Asian patients were more likely to have HIV or hepatitis C co-infection, cirrhosis, decompensated liver disease and advanced BCLC stage (all P ≤ .04). Compared with Asians, non-Asians were more likely to be listed for transplantation (P < .0001) and undergo HCC treatment with curative intent (P = .003). Propensity-score matching on HCC diagnosis year, gender and age was performed to balance the two groups for survival analysis and yielded 370 pairs of patients. There was no significant difference in survival overall (P = .43) and among patients with cirrhosis (P = .57). Among patients without cirrhosis, non-Asians had poorer 5-year survival compared with Asians (37.6% vs 53.7%, P = .01), and was associated with poorer survival after adjusting for age, gender, diabetes, alcohol, co-infections, diagnosis date, antiviral therapy, BCLC stage and HCC treatment (adjusted HR 2.01 [95% CI 1.07-3.74], P = .03). CONCLUSION Among HBV-related HCC patients, non-Asians presented with more advanced BCLC stage compared to Asians. Non-Asian ethnicity was independently associated with twice the risk of mortality among patients without cirrhosis, but not among those with cirrhosis. Additional studies are needed to clarify this disparity.
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Affiliation(s)
- Daniel Q Huang
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.,Division of Gastroenterology and Hepatology, National University Health System, Singapore
| | - Joseph K Hoang
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Jennifer Leong
- Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Mar Riveiro-Barciela
- Liver Unit, Internal Medicine Department, Hospital Universitari Valle d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain.,CIBERehd, Instituto Carlos III, Madrid, Spain
| | - Mayumi Maeda
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Ju Dong Yang
- Division of Digestive and Liver Diseases, Department of Medicine, Cedars Sinai Medical Center, Los Angeles, USA
| | - Elena Vargas Accarino
- Liver Unit, Internal Medicine Department, Hospital Universitari Valle d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain.,CIBERehd, Instituto Carlos III, Madrid, Spain
| | - Khin Thin
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Lindsey Trinh
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Ramsey C Cheung
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Lewis R Roberts
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA
| | - Maria Buti
- Liver Unit, Internal Medicine Department, Hospital Universitari Valle d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain.,CIBERehd, Instituto Carlos III, Madrid, Spain
| | - Myron Schwartz
- Recanati-Miller Transplantation Institute, Mount Sinai School of Medicine, New York, NY, USA
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA.,Department of Epidemiology and Population Health, Stanford University, Palo Alto, CA, USA
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Choi DT, Davila JA, Sansgiry S, David E, Singh H, El-Serag HB, Sada YHF. Factors Associated With Delay of Diagnosis of Hepatocellular Carcinoma in Patients With Cirrhosis. Clin Gastroenterol Hepatol 2021; 19:1679-1687. [PMID: 32693047 PMCID: PMC7855025 DOI: 10.1016/j.cgh.2020.07.026] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 07/02/2020] [Accepted: 07/15/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS We examined the frequency of and factors associated with delays in diagnosis of hepatocellular carcinoma (HCC) in a cohort of patients with cirrhosis in the Veterans Health Administration. METHODS In a retrospective study, we collected and analyzed data from the Veterans Health Administration's electronic health records. We used a multivariate logistic regression model to identify factors associated with a delay in diagnosis of HCC of more than 60 days following a red flag (defined as the earliest date at which a diagnosis of HCC could have been made, based on American Association for the Study of Liver Disease 2005 guidelines). We used multivariate Cox proportional hazards model to evaluate the effects of delayed diagnosis on survival, adjusting for patient and provider characteristics. RESULTS Among 655 patients with cirrhosis and a diagnosis of HCC from 2006 through 2011, 46.9% had a delay in diagnosis of more than 60 days following a red flag for HCC. Delays in diagnosis for more than 60 days were significantly associated with lack of provider adherence to the guidelines (adjusted odds ratio [OR], 4.82; 95% CI, 3.12-7.45), a diagnostic imaging evaluation instead of only measurement of alfa fetoprotein (adjusted OR, 2.63; 95% CI, 1.09-6.24), and diagnosis as an incidental finding during examination for an unrelated medical problem (compared with an HCC-related assessment) (adjusted OR, 2.26; 95% CI, 1.09-4.67). Diagnostic delays of 60 days or more were associated with lower mortality compared to patients without a delay in diagnosis (unadjusted hazard ratio, 0.57; 95% CI, 0.47-0.68 and adjusted hazard ratio, 0.63; 95% CI, 0.50-0.78). CONCLUSIONS Nearly half of veterans with cirrhosis have delays in diagnosis of HCC of 60 days or more after a red flag, defined by guidelines. Interventions are needed to improve timely follow-up of red flags for HCC and adherence to guidelines, to increase early detection of HCC.
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Affiliation(s)
- Debra T. Choi
- Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX,Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, TX
| | - Jessica A. Davila
- Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX,Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, TX
| | - Shubhada Sansgiry
- Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX,Veterans Affairs South Central Mental Illness Research Education and Clinical Center (MIRECC), Houston, TX,Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, TX
| | - Eric David
- Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX
| | - Hardeep Singh
- Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX,Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, TX
| | - Hashem B. El-Serag
- Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX,Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX,Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, TX
| | - Yvonne Hsiao-Fan Sada
- Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX,Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX,Section of Hematology and Oncology, Department of Medicine, Baylor College of Medicine, Houston, TX
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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: 11] [Impact Index Per Article: 2.8] [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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Samant H, Amiri HS, Zibari GB. Addressing the worldwide hepatocellular carcinoma: epidemiology, prevention and management. J Gastrointest Oncol 2021; 12:S361-S373. [PMID: 34422400 PMCID: PMC8343080 DOI: 10.21037/jgo.2020.02.08] [Citation(s) in RCA: 84] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2019] [Accepted: 01/22/2020] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world with rising incidence. Globally, there has been substantial variation in prevalence of risk factors for HCC over years, like control of viral hepatitis in developing countries but growing epidemic of fatty liver disease in developed world. Changing epidemiology of HCC is related to trends in these risk factors. HCC remains asymptomatic until it is very advanced which makes early detection by surveillance important in reducing HCC related mortality. Management of HCC. depends on stage of the tumor and severity of underlying liver disease. At present, resection and transplant are still the best curative options for small HCC, but recent advances in locoregional therapy and molecular targeted systemic therapy has changed the management for HCC at intermediate and advanced stages. This review is overview of global epidemiology, prevention, surveillance and emerging therapies for hepatocellular carcinoma.
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Affiliation(s)
- Hrishikesh Samant
- Division of Gastroenterology and Hepatology, LSU Health Science Center, Shreveport, LA, USA
| | - Hosein Shokouh Amiri
- John C McDonald Transplant Center, Willis Knighton Health System, Shreveport, LA, USA
| | - Gazi B. Zibari
- John C McDonald Transplant Center, Willis Knighton Health System, Shreveport, LA, USA
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44
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Fuster D, García-Calvo X, Zuluaga P, Bolao F, Muga R. Assessment of liver disease in patients with chronic hepatitis C and unhealthy alcohol use. World J Gastroenterol 2021; 27:3223-3237. [PMID: 34163107 PMCID: PMC8218351 DOI: 10.3748/wjg.v27.i23.3223] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 03/11/2021] [Accepted: 05/10/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infection and unhealthy alcohol use are major drivers of the burden of liver disease worldwide and commonly co-occur. Assessment of underlying liver damage is a cornerstone of the clinical care of patients with chronic HCV infection and/or unhealthy alcohol use because many of them are diagnosed at advanced stages of disease. Early diagnosis of liver disease before decompensated liver cirrhosis becomes established is essential for treatment with direct acting antivirals and/or abstinence from alcohol consumption, which are the main therapeutic approaches for clinical management. In this review, we discuss current knowledge around the use of non-invasive methods to assess liver disease, such as abdominal ultrasound, controlled attenuation parameter, transient elastography, magnetic resonance imaging, and indices based on serum markers of liver injury.
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Affiliation(s)
- Daniel Fuster
- Department of Internal Medicine, Addiction Unit, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona 08916, Spain
| | - Xavier García-Calvo
- Department of Internal Medicine, Addiction Unit, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona 08916, Spain
| | - Paola Zuluaga
- Department of Internal Medicine, Addiction Unit, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona 08916, Spain
| | - Ferran Bolao
- Department of Internal Medicine, Hospital Universitari Bellvitge, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona 08907, Spain
| | - Robert Muga
- Department of Internal Medicine, Addiction Unit, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona 08916, Spain
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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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Shaltiel T, Zheng S, Siderides C, Gleeson EM, Carr J, Pletcher ER, Cohen NA, Golas BJ, Magge DR, Labow DM, Branch AD, Sarpel U. Hepatitis C-positive Black patients develop hepatocellular carcinoma at earlier stages of liver disease and present with a more aggressive phenotype. Cancer 2021; 127:1395-1406. [PMID: 33629759 PMCID: PMC8084866 DOI: 10.1002/cncr.33377] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 08/28/2020] [Accepted: 09/07/2020] [Indexed: 12/23/2022]
Abstract
BACKGROUND In the United States, mortality after a diagnosis of hepatocellular carcinoma (HCC) is higher in patients who are Black than in patients of other racial groups. The objective of this study was to clarify factors contributing to this disparity by analyzing liver and tumor characteristics in patients with HCC who have a history of hepatitis C virus (HCV) infection. METHODS Records of patients with HCV and HCC at the authors' institution from 2003 to 2018 were retrospectively reviewed. Race and ethnicity were self-identified. Imaging, laboratory, and pathologic features were compared between Black and non-Black cohorts. RESULTS Among 1195 individuals with HCC, 390 identified as Black. At the time of HCC diagnosis, Black patients had better liver function, as measured by Child-Pugh score, Model of End-Stage Liver Disease score, histology of nontumor tissue, and fibrosis-4 (FIB-4) score (all P < .05). FIB-4 scores were <3.25 in 31% of Black patients. In addition, Black patients had less early stage HCC (20.2% vs 32.3%; P < .05), larger tumors (median [interquartile range]: 3.5 cm [2.2-6.2 cm] vs 3.1 cm [2.1-5.1 cm]; P < .01), more multiple tumors (median, [interquartile range]: 1 tumor [1-3 tumors] vs 1 tumor [1-2 tumors]; P = .03), more poorly differentiated tumors (30.3% vs 20.5%; P < .05), and more microvascular invasion (67.2% vs 56.5%; P < .05). CONCLUSIONS Black patients with HCV exposure develop HCC at earlier stages of liver disease than members of other racial groups. Nearly one-third would not qualify for HCC screening using the common FIB-4 cirrhosis threshold. Practice guidelines that stress HCC surveillance for cirrhotic patients with HCV may need to be revised to be more inclusive for Black patients. In addition, tumors in Black patients carry worse prognostic features, and molecular studies are needed to characterize their biologic properties.
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Affiliation(s)
- Tali Shaltiel
- Department of Surgery, Division of Surgical Oncology, New York, NY
| | - Serena Zheng
- Icahn School of Medicine at Mount Sinai, New York, NY
| | | | | | - Jacquelyn Carr
- Department of Surgery, Division of Surgical Oncology, New York, NY
| | - Eric R. Pletcher
- Department of Surgery, Division of Surgical Oncology, New York, NY
| | - Noah A. Cohen
- Department of Surgery, Division of Surgical Oncology, New York, NY
| | | | - Deepa R. Magge
- Department of Surgery, Division of Surgical Oncology, New York, NY
| | - Daniel M. Labow
- Department of Surgery, Division of Surgical Oncology, New York, NY
| | - Andrea D. Branch
- Department of Medicine, Division of Liver Diseases, New York, NY
| | - Umut Sarpel
- Department of Surgery, Division of Surgical Oncology, New York, NY
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47
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Singal AG, Tiro JA, Murphy CC, Blackwell JM, Kramer JR, Khan A, Liu Y, Zhang S, Phillips JL, Hernaez R. Patient-Reported Barriers Are Associated With Receipt of Hepatocellular Carcinoma Surveillance in a Multicenter Cohort of Patients With Cirrhosis. Clin Gastroenterol Hepatol 2021; 19:987-995.e1. [PMID: 32629122 PMCID: PMC7779689 DOI: 10.1016/j.cgh.2020.06.049] [Citation(s) in RCA: 83] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Revised: 06/04/2020] [Accepted: 06/22/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND More than 20% of patients with cirrhosis do not receive semi-annual hepatocellular carcinoma (HCC) surveillance as recommended. Few studies have evaluated the effects of patient-level factors on surveillance receipt. METHODS We administered a telephone survey to a large cohort of patients with cirrhosis from 3 health systems (a tertiary care referral center, a safety-net health system, and Veterans Affairs) to characterize patient knowledge, attitudes, and perceived barriers of HCC surveillance. Multinomial logistic regression was performed to identify factors associated with HCC surveillance receipt (semi-annual and annual vs none) during the 12-month period preceding survey administration. RESULTS Of 2871 patients approached, 1020 (35.5%) completed the survey. Patients had high levels of concern about developing HCC and high levels of knowledge about HCC. However, patients had knowledge deficits, including believing surveillance was unnecessary when physical examination and laboratory results were normal. Nearly half of patients reported barriers to surveillance, including costs (28.9%), difficulty scheduling (24.1%), and transportation (17.8%). In the year before the survey, 745 patients (73.1%) received 1 or more surveillance examination; 281 received on-schedule, semi-annual surveillance and 464 received annual surveillance. Semi-annual HCC surveillance (vs none) was significantly associated with receipt of hepatology subspecialty care (odds ratio, 30.1; 95% CI, 17.5-51.8) and inversely associated with patient-reported barriers (odds ratio, 0.62; 95% CI, 0.41-0.94). Patterns of associations comparing annual vs no surveillance were similar although the magnitude of effects were reduced. CONCLUSIONS Patient-reported barriers such as knowledge deficits, costs, difficulty scheduling, and transportation are significantly associated with less frequent receipt of HCC surveillance, indicating a need for patient-centered interventions, such as patient navigation.
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Affiliation(s)
- Amit G Singal
- Department of Internal Medicine, UT Southwestern Medical Center and Parkland Health Hospital System, Dallas, Texas; Harold C. Simmons Cancer Center, UT Southwestern Medical Center, Dallas, Texas; Department of Clinical Sciences, UT Southwestern Medical Center, Dallas, Texas.
| | - Jasmin A Tiro
- Department of Clinical Sciences, UT Southwestern Medical Center, Dallas, Texas
| | - Caitlin C Murphy
- Department of Clinical Sciences, UT Southwestern Medical Center, Dallas, Texas
| | | | - Jennifer R Kramer
- Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
| | - Aisha Khan
- Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
| | - Yan Liu
- Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
| | - Song Zhang
- Department of Clinical Sciences, UT Southwestern Medical Center, Dallas, Texas
| | - Jessica L Phillips
- Department of Clinical Sciences, UT Southwestern Medical Center, Dallas, Texas
| | - Ruben Hernaez
- Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas; Department of Medicine, Baylor College of Medicine, Houston, Texas
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48
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Vo Quang E, Shimakawa Y, Nahon P. Epidemiological projections of viral-induced hepatocellular carcinoma in the perspective of WHO global hepatitis elimination. Liver Int 2021; 41:915-927. [PMID: 33641230 DOI: 10.1111/liv.14843] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 01/19/2021] [Accepted: 02/13/2021] [Indexed: 12/13/2022]
Abstract
Hepatitis B is an eminent risk factor for hepatocellular carcinoma (HCC) in Southeast Asia and sub-Saharan Africa, whereas hepatitis C is a key risk factor for HCC in Western Europe and North America. Increased awareness of the global burden of viral hepatitis resulted, in May 2016, in the adoption of the first global health sector strategy on viral hepatitis by the World Health Assembly, which calls for the elimination of viral hepatitis as a public health threat by 2030. Although the incidence of liver cancer resulting from viral infections has increased since the 1990s, the implementation of public health interventions, such as hepatitis B vaccination and antiviral therapies might have reduced the global burdens of HCC. Hepatitis B immunization in infancy has been associated with a reduction in the risk of infant fulminant hepatitis, chronic liver disease, and HCC in Taiwan. Achieving viral hepatitis elimination by 2030 can be accelerated by improving the access to HCC screening programs. HCC surveillance programs in developed countries must be refined to increase an access to personalized surveillance program, whereas the limited access to surveillance and treatment of HCC in developing countries remains a significant public health issue.
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Affiliation(s)
- Erwan Vo Quang
- Université Paris-Sud, Université Paris-Saclay, Kremlin-Bicêtre, France.,AP-HP, Hôpital Avicenne, Service d'Hépatologie, Bobigny, France.,Equipe labellisée Ligue Contre le Cancer, Université Paris 13, Sorbonne Paris Cité, Saint-Denis, France.,Inserm, UMR-1162, Génomique fonctionnelle des tumeurs solides, Paris, France
| | - Yusuke Shimakawa
- Unité d'Epidémiologie des Maladies Emergentes, Institut Pasteur, Paris, France
| | - Pierre Nahon
- AP-HP, Hôpital Avicenne, Service d'Hépatologie, Bobigny, France.,Equipe labellisée Ligue Contre le Cancer, Université Paris 13, Sorbonne Paris Cité, Saint-Denis, France.,Inserm, UMR-1162, Génomique fonctionnelle des tumeurs solides, Paris, France
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49
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Moon AM, Sanoff HK, Chang Y, Lund JL, Barritt AS, Hayashi PH, Stitzenberg KB. Medicare/Medicaid Insurance, Rurality, and Black Race Associated With Provision of Hepatocellular Carcinoma Treatment and Survival. J Natl Compr Canc Netw 2021; 19:285-293. [PMID: 33578376 PMCID: PMC9899074 DOI: 10.6004/jnccn.2020.7616] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Accepted: 07/01/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Early treatment of hepatocellular carcinoma (HCC) is associated with improved survival, but many patients with HCC do not receive therapy. We aimed to examine factors associated with HCC treatment and survival among incident patients with HCC in a statewide cancer registry. MATERIALS AND METHODS All patients with HCC from 2003 through 2013 were identified in the North Carolina cancer registry. These patients were linked to insurance claims from Medicare, Medicaid, and large private insurers in North Carolina. Associations between prespecified covariates and more advanced HCC stage at diagnosis (ie, multifocal cancer), care at a liver transplant center, and provision of HCC treatment were examined using multivariate logistic regression. A Cox proportional hazards model was developed to assess the association between these factors and survival. RESULTS Of 1,809 patients with HCC, 53% were seen at a transplant center <90 days from diagnosis, with lower odds among those who were Black (adjusted odds ratio [aOR], 0.54; 95% CI, 0.39-0.74), had Medicare insurance (aOR, 0.35; 95% CI, 0.21-0.59), had Medicaid insurance (aOR, 0.46; 95% CI, 0.28-0.77), and lived in a rural area; odds of transplant center visits were higher among those who had prediagnosis alpha fetoprotein screening (aOR, 1.74; 95% CI, 1.35-2.23) and PCP and gastroenterology care (aOR, 1.66; 95% CI, 1.27-2.18). Treatment was more likely among patients who had prediagnosis gastroenterology care (aOR, 1.68; 95% CI, 0.98-2.86) and transplant center visits (aOR, 2.42; 95% CI, 1.74-3.36). Survival was strongly associated with age, cancer stage, cirrhosis complications, and receipt of HCC treatment. Individuals with Medicare (adjusted hazard ratio [aHR], 1.58; 95% CI, 1.20-2.09) and Medicaid insurance (aHR, 1.55; 95% CI, 1.17-2.05) had shorter survival than those with private insurance. CONCLUSIONS In this population-based cohort of patients with HCC, Medicare/Medicaid insurance, rural residence, and Black race were associated with lower provision of HCC treatment and poorer survival. Efforts should be made to improve access to care for these vulnerable populations.
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Affiliation(s)
- Andrew M. Moon
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill NC
| | - Hanna K. Sanoff
- Division of Hematology/Oncology, Department of Medicine, University of North Carolina, Chapel Hill NC,Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill NC
| | - YunKyung Chang
- Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill NC
| | - Jennifer L. Lund
- Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill NC,,Center for Pharmacoepidemiology, Department of Epidemiology, University of North Carolina, Chapel Hill NC
| | - A. Sidney Barritt
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill NC
| | - Paul H. Hayashi
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill NC
| | - Karyn B. Stitzenberg
- Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill NC,,Division of Surgical Oncology, Department of Surgery, University of North Carolina, Chapel Hill NC
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50
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Wolf E, Rich NE, Marrero JA, Parikh ND, Singal AG. Use of Hepatocellular Carcinoma Surveillance in Patients With Cirrhosis: A Systematic Review and Meta-Analysis. Hepatology 2021; 73:713-725. [PMID: 32383272 PMCID: PMC7648722 DOI: 10.1002/hep.31309] [Citation(s) in RCA: 197] [Impact Index Per Article: 49.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Accepted: 04/21/2020] [Indexed: 12/24/2022]
Abstract
BACKGROUND AND AIMS Hepatocellular carcinoma (HCC) surveillance is associated with early tumor detection and improved survival; however, it is often underused in clinical practice. We aimed to characterize surveillance use among patients with cirrhosis and the efficacy of interventions to increase surveillance. APPROACH AND RESULTS We performed a systematic literature review using the MEDLINE database from January 2010 through August 2018 to identify cohort studies evaluating HCC surveillance receipt or interventions to increase surveillance in patients with cirrhosis. A pooled estimate for surveillance receipt with 95% confidence intervals was calculated. Correlates of surveillance use were defined from each study and prespecified subgroup analyses. Twenty-nine studies, with a total of 118,799 patients, met inclusion criteria, with a pooled estimate for surveillance use of 24.0% (95% confidence interval, 18.4-30.1). In subgroup analyses, the highest surveillance receipt was reported in studies with patients enrolled from subspecialty gastroenterology/hepatology clinics and lowest in studies characterizing surveillance in population-based cohorts (73.7% versus 8.8%, P < 0.001). Commonly reported correlates of surveillance included higher receipt among patients followed by subspecialists and lower receipt among those with alcohol-associated or nonalcoholic steatohepatitis (NASH)-related cirrhosis. All eight studies (n = 5,229) evaluating interventions including patient/provider education, inreach (e.g., reminder and recall systems), and population health outreach strategies reported significant increases (range 9.4%-63.6%) in surveillance receipt. CONCLUSIONS HCC surveillance remains underused in clinical practice, particularly among patients with alcohol-associated or NASH-related cirrhosis and those not followed in subspecialty gastroenterology clinics. Interventions such as provider education, inreach including reminder systems, and population health outreach efforts can significantly increase HCC surveillance.
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Affiliation(s)
- Erin Wolf
- Department of Internal MedicineUT Southwestern Medical CenterDallasTXUSA
| | - Nicole E Rich
- Department of Internal MedicineUT Southwestern Medical CenterDallasTXUSA
| | - Jorge A Marrero
- Department of Internal MedicineUT Southwestern Medical CenterDallasTXUSA
| | - Neehar D Parikh
- Department of Internal MedicineUniversity of MichiganAnn ArborMIUSA
| | - Amit G Singal
- Department of Internal MedicineUT Southwestern Medical CenterDallasTXUSA
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