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Brahmania M, Congly S, Sachar Y, Burak KW, Lethebe B, Szostakiwskyj JH, Lautner D, Medellin A, Bhayana D, Wong J, Nguyen H, Sadler MD, Borman M, Aspinall AI, Coffin CS, Swain M, Shaheen A. Dedicated Automatic Recall Hepatocellular Cancer Surveillance Programme Demonstrates High Retention: A Population-Based Cohort Study. Liver Int 2025; 45:e70020. [PMID: 39927626 PMCID: PMC11809127 DOI: 10.1111/liv.70020] [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: 06/18/2024] [Revised: 12/28/2024] [Accepted: 01/27/2025] [Indexed: 02/11/2025]
Abstract
INTRODUCTION Patient, clinician, and system-related barriers may affect adherence to hepatocellular carcinoma (HCC) surveillance programmes. The impact of a dedicated automated recall HCC surveillance programme on retention rates in patients eligible for screening is unknown. We aimed to describe and evaluate a large HCC surveillance programme in a publicly funded healthcare system. METHODS Data were collected from January 1, 2013, to December 31, 2022, from a retrospective cohort of subjects enrolled in a publicly funded automated recall semi-annual surveillance programme as per the American Association for the Study of Liver Disease HCC guidance in the Calgary Health Zone (~1.6 million), Canada. Patients were excluded if there was incomplete data or did not meet indications for surveillance. Cox regression was used to identify predictors of non-retention to surveillance. RESULTS A total of 7269 patients were included. The median was age 55.5 years (IQR: 45.5-63.8), 60% were male, 46% were of Asian descent, 51% had HBV infection, and 36% had cirrhosis (35% alcohol-related). Median follow-up was 4.9 years (IQR: 1.5-7.2). Overall, 52% (n = 3768) of patients were retained in the surveillance programme, while 8.3% (n = 603) left for potential medical reasons, and 40% (n = 2898) were lost in follow-up. The median time in the programme for those lost in follow-up was 0.81 years (IQR: 0.0-2.8) compared to 6.75 years if retained (IQR: 5.6-8.6; p < 0.001). In multivariable Cox regression analysis, HCV aetiology (HR 1.41; CI 1.23-1.62, p < 0.01), African ethnicity (HR 1.20, CI 1.02-1.42, p = 0.03), and cirrhosis (HR 1.16, CI 1.05-1.28, p < 0.01) increased risk of dropout. On interaction analysis, Hepatitis B amongst cirrhotic patients also increased risk of dropout (HR 1.48, CI 1.05-2.07, p = 0.02). CONCLUSION A dedicated automated recall HCC surveillance programme has a high retention rate in a large multi-ethnic cohort of patients while identifying certain marginalised patient populations, such as those with viral liver disease, cirrhosis, or African ethnicity, as particularly vulnerable to loss to follow-up.
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Affiliation(s)
- Mayur Brahmania
- Division of Gastroenterology and Hepatology, Department of MedicineSchulich School of MedicineLondonOntarioCanada
- O'Brien Institute of Public HealthSchulich School of MedicineLondonOntarioCanada
| | - Stephen Congly
- Division of Gastroenterology and Hepatology, Department of MedicineSchulich School of MedicineLondonOntarioCanada
- O'Brien Institute of Public HealthSchulich School of MedicineLondonOntarioCanada
| | - Yashasavi Sachar
- Division of Internal Medicine, Department of MedicineSchulich School of MedicineLondonOntarioCanada
| | - Kelly W. Burak
- Division of Gastroenterology and Hepatology, Department of MedicineSchulich School of MedicineLondonOntarioCanada
- Department of OncologyCumming School of MedicineCalgaryAlbertaCanada
| | - Brendan Lethebe
- Clinical Research UnitCumming School of Medicine, University of CalgaryCalgaryAlbertaCanada
| | | | - David Lautner
- Department of RadiologyCumming School of Medicine, University of CalgaryCalgaryAlbertaCanada
| | - Alexandra Medellin
- Department of RadiologyCumming School of Medicine, University of CalgaryCalgaryAlbertaCanada
| | - Deepak Bhayana
- Department of RadiologyCumming School of Medicine, University of CalgaryCalgaryAlbertaCanada
| | - Jason Wong
- Department of RadiologyCumming School of Medicine, University of CalgaryCalgaryAlbertaCanada
| | - Henry Nguyen
- Division of Gastroenterology and Hepatology, Department of MedicineSchulich School of MedicineLondonOntarioCanada
| | - Matthew D. Sadler
- Division of Gastroenterology and Hepatology, Department of MedicineSchulich School of MedicineLondonOntarioCanada
| | - Meredith Borman
- Division of Gastroenterology and Hepatology, Department of MedicineSchulich School of MedicineLondonOntarioCanada
| | - Alexander I. Aspinall
- Division of Gastroenterology and Hepatology, Department of MedicineSchulich School of MedicineLondonOntarioCanada
| | - Carla S. Coffin
- Division of Gastroenterology and Hepatology, Department of MedicineSchulich School of MedicineLondonOntarioCanada
| | - Mark Swain
- Division of Gastroenterology and Hepatology, Department of MedicineSchulich School of MedicineLondonOntarioCanada
| | - Abdel‐Aziz Shaheen
- Division of Gastroenterology and Hepatology, Department of MedicineSchulich School of MedicineLondonOntarioCanada
- O'Brien Institute of Public HealthSchulich School of MedicineLondonOntarioCanada
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Hui S, Sane N, Wang A, Wan L, Bell S, Le S, Dev A. Hepatocellular carcinoma surveillance in the telehealth era: A single-centre review. J Telemed Telecare 2025; 31:64-72. [PMID: 37032467 DOI: 10.1177/1357633x231166032] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/11/2023]
Abstract
BACKGROUND Real-world hepatocellular carcinoma (HCC) surveillance uptake remains suboptimal, despite evidence that surveillance is associated with lower cancer-related mortality in patients with cirrhosis and chronic hepatitis B. We aimed to examine the impact of telehealth consultations on HCC surveillance rates within a specialist liver clinic. METHODS We conducted a retrospective observational study within an Australian outreach liver clinic within a culturally diverse community, comparing standard consultations before the COVID-19 pandemic to telehealth consultations during the pandemic. The primary outcome was surveillance uptake defined as the percentage of time up-to-date with surveillance (PTUDS) with the 6-month interval following each scan considered up-to-date. RESULTS Over 18 months of follow-up for each cohort, the median PTUDS was 86.5% in the standard consultation cohort and 85.5% in the telehealth consultation cohort (p = 0.12). HCC diagnoses did not differ between groups and hospitalisation and mortality rates were low. Using multivariate regression, increasing age, the need for an interpreter and being born in South-East Asia independently predicted PTUDS in the standard consultation cohort, whereas being born in Australia or New Zealand was predictive of a lower PTUDS. Current alcohol use and distance from the clinic predicted a lower PTUDS in the telehealth consultation cohort. In both groups, missed clinic attendances were strongly predictive of a lower PTUDS. CONCLUSION Telehealth hepatology consultations effectively coordinate HCC surveillance and are associated with similar outcomes to standard consultations. Its implementation should be widely considered given its advantages with regards to accessibility for patients.
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Affiliation(s)
- Samuel Hui
- School of Clinical Sciences at Monash Health, Monash University, Melbourne, Victoria, Australia
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, Victoria, Australia
| | - Nikhita Sane
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, Victoria, Australia
| | - Andrew Wang
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, Victoria, Australia
| | - Leo Wan
- School of Clinical Sciences at Monash Health, Monash University, Melbourne, Victoria, Australia
| | - Sally Bell
- School of Clinical Sciences at Monash Health, Monash University, Melbourne, Victoria, Australia
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, Victoria, Australia
| | - Suong Le
- School of Clinical Sciences at Monash Health, Monash University, Melbourne, Victoria, Australia
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, Victoria, Australia
| | - Anouk Dev
- School of Clinical Sciences at Monash Health, Monash University, Melbourne, Victoria, Australia
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, Victoria, Australia
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Goldberg D, Reese PP, Kaplan DA, Zarnegarnia Y, Gaddipati N, Gaddipati S, John B, Blandon C. Predicting long-term survival among patients with HCC. Hepatol Commun 2024; 8:e0581. [PMID: 39495142 PMCID: PMC11537595 DOI: 10.1097/hc9.0000000000000581] [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: 07/25/2024] [Accepted: 09/03/2024] [Indexed: 11/05/2024] Open
Abstract
BACKGROUND Prognosticating survival among patients with HCC and cirrhosis must account for both the tumor burden/stage, as well as the severity of the underlying liver disease. Although there are many staging systems used to guide therapy, they have not been widely adopted to predict patient-level survival after the diagnosis of HCC. We sought to develop a score to predict long-term survival among patients with early- to intermediate-stage HCC using purely objective criteria. METHODS Retrospective cohort study among patients with HCC confined to the liver, without major medical comorbidities within the Veterans Health Administration from 2014 to 2023. Tumor data were manually abstracted and combined with clinical and laboratory data to predict 5-year survival from HCC diagnosis using accelerated failure time models. The data were randomly split using a 75:25 ratio for training and validation. Model discrimination and calibration were assessed and compared to other HCC staging systems. RESULTS The cohort included 1325 patients with confirmed HCC. A risk score using baseline clinical, laboratory, and HCC-related survival had excellent discrimination (integrated AUC: 0.71 in the validation set) and calibration (based on calibration plots and Brier scores). Models had superior performance to the BCLC and ALBI scores and similar performance to the combined BCLC-ALBI score. CONCLUSIONS We developed a risk score using purely objective data to accurately predict long-term survival for patients with HCC. This score, if validated, can be used to prognosticate survival for patients with HCC, and, in the setting of liver transplantation, can be incorporated to consider the net survival benefit of liver transplantation versus other curative options.
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Affiliation(s)
- David Goldberg
- Department of Medicine, Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, Miami, Florida, USA
- Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, Florida, USA
- Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Peter P. Reese
- Department of Medicine, Renal-Electrolyte and Hypertension Division, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
- Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - David A. Kaplan
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
- Department of Medicine, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA
| | - Yalda Zarnegarnia
- Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Neelima Gaddipati
- Department of Medicine, Jackson Memorial Hospital, Miami, Florida, USA
| | - Sirisha Gaddipati
- Department of Medicine, Jackson Memorial Hospital, Miami, Florida, USA
| | - Binu John
- Department of Medicine, Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, Miami, Florida, USA
- Department of Medicine, Bruce Carter VA Medical Center, Miami, Florida, USA
| | - Catherine Blandon
- Department of Medicine, Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, Miami, Florida, USA
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Qurashi M, von Wagner C, Sharma R. Optimising Surveillance in Hepatocellular Carcinoma: Patient-Defined Obstacles and Solutions. J Hepatocell Carcinoma 2024; 11:1597-1605. [PMID: 39193064 PMCID: PMC11348922 DOI: 10.2147/jhc.s462303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Accepted: 07/20/2024] [Indexed: 08/29/2024] Open
Abstract
Background and Aims Six-monthly ultrasound surveillance for hepatocellular carcinoma (HCC) is recommended in patients with cirrhosis. Surveillance enhances early detection and improves survival. Yet, despite clear benefits, uptake remains low. We aim to identify and explore ways to overcome patient-related barriers to HCC surveillance with the aim of producing invitations for surveillance. Methods Using the COM-B model of behaviour and a co-design process, we collaborated with patients, liver health charities and advocacy groups, to identify patient-related barriers to attending HCC surveillance. We performed qualitative thematic analysis of co-production workshops on HCC surveillance to develop information leaflets and surveillance invitations. Results Twenty-eight participants attended five workshops. Fear of a serious diagnosis and stigma from healthcare professionals were highlighted as main patient-related barriers to attending surveillance appointments. Co-design was used to develop informative, user-friendly, non-judgemental invitations and information regarding HCC surveillance relevant to populations with cirrhosis. Conclusion We identified potential patient barriers to surveillance uptake and developed patient facing material that directly addressed these barriers to be trialled in the clinic. Targeting patient-specific barriers may increase uptake of surveillance and therefore enhance early diagnosis.
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Affiliation(s)
- Maria Qurashi
- Department of Surgery & Cancer, Imperial College London, London, UK
| | - Christian von Wagner
- Department of Epidemiology and Public Health, University College London, London, UK
| | - Rohini Sharma
- Department of Surgery & Cancer, Imperial College London, London, UK
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Hui S, Nguyen A, Le S, Dev A, Bell S. Clinical outcomes of hepatocellular carcinoma surveillance in Melbourne, Australia. Intern Med J 2024; 54:1360-1368. [PMID: 38666599 DOI: 10.1111/imj.16405] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Accepted: 03/28/2024] [Indexed: 08/20/2024]
Abstract
BACKGROUND Ultrasound surveillance for hepatocellular carcinoma (HCC) may improve early tumour detection but may additionally result in surveillance-related harm through increased evaluation of non-HCC lesions. The incidence of these outcomes has not been reported outside North America. AIMS We aimed to report the outcomes of HCC surveillance with respect to both surveillance-related benefits and harms. METHODS We reviewed all HCC surveillance ultrasounds at a large Victorian tertiary hospital network in 2017 and followed their outcomes until 2021. Surveillance-related benefits were defined as early-stage HCC detection. Surveillance-related harm was defined as contrast imaging, biopsies or surgery performed to evaluate non-HCC liver lesions or false-positive alpha-fetoprotein levels. RESULTS Five hundred and fifty-three patients were included (mean age 54.5 ± 12.3 years, males 67.5%, cirrhosis 50.3%). The most common liver disease aetiology was hepatitis B (53.9%). Over a median of 4.7 years follow-up, early-stage HCC was detected in 3.3% (5.4% in cirrhotic vs 1.1% in non-cirrhotic patients, P < 0.01). 75% of all HCCs were early-stage. Surveillance-related harm occurred in 12.5% (15.5% in cirrhotic vs 9.5% in non-cirrhotic patients, P < 0.04), although most harm was mild (12.1%). In subgroup analysis, the detection of early-stage HCC ranged between 0% (screened outside of guideline criteria and alcoholic cirrhotic patients) and 7.2% (hepatitis C cirrhosis). Harm occurred between 9% (non-cirrhotic hepatitis B) and 20.8% (thrombocytopenia). CONCLUSION In our study, HCC surveillance was associated with early tumour detection, although many patients experienced mild surveillance-related harm. Novel surveillance strategies and pathways are required to improve detection in high-risk patients and minimise harm in low-risk patients.
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Affiliation(s)
- Samuel Hui
- Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, Victoria, Australia
| | - Andrew Nguyen
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, Victoria, Australia
| | - Suong Le
- Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, Victoria, Australia
| | - Anouk Dev
- Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, Victoria, Australia
| | - Sally Bell
- Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, Victoria, Australia
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Mezzacappa C, Kim NJ, Vutien P, Kaplan DE, Ioannou GN, Taddei TH. Screening for Hepatocellular Carcinoma and Survival in Patients With Cirrhosis After Hepatitis C Virus Cure. JAMA Netw Open 2024; 7:e2420963. [PMID: 38985470 PMCID: PMC11238019 DOI: 10.1001/jamanetworkopen.2024.20963] [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: 02/01/2024] [Accepted: 05/05/2024] [Indexed: 07/11/2024] Open
Abstract
Importance The risk of hepatocellular carcinoma (HCC) declines over time after hepatitis C virus (HCV) cure by direct-acting antiviral (DAA) therapies. Liver society guidelines recommend continuing HCC screening for these patients, but data on screening outcomes are lacking. Objective To evaluate the association of HCC screening after HCV cure with overall survival. Design, Setting, and Participants This cohort study evaluated patients with HCV cirrhosis who achieved DAA-induced HCV cure in the Veterans Affairs health care system between January 2014 and December 2022. Data analysis occurred from October 2023 to January 2024. Exposures The percentage of time spent up to date with recommended HCC screening was calculated by year of follow-up and during the 4 years preceding HCC diagnosis (the detectable asymptomatic phase). Main Outcomes and Measures The primary outcome was overall survival after HCC diagnosis and was compared by percentage of time spent up to date with screening using Kaplan-Meier analyses and Cox proportional hazards regression. Early-stage HCC at diagnosis and curative treatment were secondary outcomes assessed using logistic regression. Results A total of 16 902 individuals were included (median [IQR] age, 64.0 [60.5-67.4] years; 16 426 male [97.2%]), of whom 1622 developed HCC. The cumulative incidence of HCC declined from 2.4% (409 of 16 902 individuals) to 1.0% (27 of 2833 individuals) from year 1 to year 7 of follow-up. Being up to date with screening for at least 50% of time during the 4 years preceding HCC diagnosis was associated with improved overall survival (log-rank test of equality over strata P = .002). In multivariate analysis, each 10% increase in follow-up spent up to date with screening was associated with a 3.2% decrease in the hazard of death (hazard ratio, 0.97; 95% CI, 0.95-0.99). There was a statistically significant interaction between time since HCV cure and screening, with no association observed among those who received a diagnosis of HCC more than 5 years after HCV cure. Each 10% of time spent up to date with screening was associated with a 10.1% increased likelihood of diagnosis with early-stage HCC (95% CI, 6.3%-14.0%) and a 6.8% increased likelihood of curative treatment (95% CI, 2.8%-11.0%). Conclusions and Relevance In this cohort study of persons with HCV-related cirrhosis who achieved HCV cure and subsequently developed HCC, remaining up to date with screening was associated with improved overall survival, supporting the screening of eligible individuals.
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Affiliation(s)
- Catherine Mezzacappa
- Division of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut
- Gastroenterology Section, VA Connecticut Healthcare System, West Haven, Connecticut
| | - Nicole J. Kim
- Division of Gastroenterology, University of Washington, Seattle
- Gastroenterology Division, VA Puget Sound Health Care System, Seattle, Washington
| | - Philip Vutien
- Division of Gastroenterology, University of Washington, Seattle
- Gastroenterology Division, VA Puget Sound Health Care System, Seattle, Washington
| | - David E. Kaplan
- Division of Gastroenterology and Hepatology, University of Pennsylvania School of Medicine, Philadelphia
- Gastroenterology Section, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania
| | - George N. Ioannou
- Division of Gastroenterology, University of Washington, Seattle
- Gastroenterology Division, VA Puget Sound Health Care System, Seattle, Washington
| | - Tamar H. Taddei
- Division of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut
- Gastroenterology Section, VA Connecticut Healthcare System, West Haven, Connecticut
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He L, Ji WS, Jin HL, Lu WJ, Zhang YY, Wang HG, Liu YY, Qiu S, Xu M, Lei ZP, Zheng Q, Yang XL, Zhang Q. Development of a nomogram for predicting liver transplantation prognosis in hepatocellular carcinoma. World J Gastroenterol 2024; 30:2763-2776. [PMID: 38899335 PMCID: PMC11185292 DOI: 10.3748/wjg.v30.i21.2763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Revised: 04/24/2024] [Accepted: 05/13/2024] [Indexed: 06/03/2024] Open
Abstract
BACKGROUND At present, liver transplantation (LT) is one of the best treatments for hepatocellular carcinoma (HCC). Accurately predicting the survival status after LT can significantly improve the survival rate after LT, and ensure the best way to make rational use of liver organs. AIM To develop a model for predicting prognosis after LT in patients with HCC. METHODS Clinical data and follow-up information of 160 patients with HCC who underwent LT were collected and evaluated. The expression levels of alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin, Golgi protein 73, cytokeratin-18 epitopes M30 and M65 were measured using a fully automated chemiluminescence analyzer. The best cutoff value of biomarkers was determined using the Youden index. Cox regression analysis was used to identify the independent risk factors. A forest model was constructed using the random forest method. We evaluated the accuracy of the nomogram using the area under the curve, using the calibration curve to assess consistency. A decision curve analysis (DCA) was used to evaluate the clinical utility of the nomograms. RESULTS The total tumor diameter (TTD), vascular invasion (VI), AFP, and cytokeratin-18 epitopes M30 (CK18-M30) were identified as important risk factors for outcome after LT. The nomogram had a higher predictive accuracy than the Milan, University of California, San Francisco, and Hangzhou criteria. The calibration curve analyses indicated a good fit. The survival and recurrence-free survival (RFS) of high-risk groups were significantly lower than those of low- and middle-risk groups (P < 0.001). The DCA shows that the model has better clinical practicability. CONCLUSION The study developed a predictive nomogram based on TTD, VI, AFP, and CK18-M30 that could accurately predict overall survival and RFS after LT. It can screen for patients with better postoperative prognosis, and improve long-term survival for LT patients.
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Affiliation(s)
- Li He
- Department of Organ Transplantation, The Third Medical Centre of Chinese PLA General Hospital, Beijing 100039, China
- School of Clinical Medicine, Shandong Second Medical University, Weifang 261053, Shandong Province, China
| | - Wan-Sheng Ji
- Clinical Research Center, The Affiliated Hospital of Shandong Second Medical University, Weifang 261053, Shandong Province, China
| | - Hai-Long Jin
- Department of Organ Transplantation, The Third Medical Centre of Chinese PLA General Hospital, Beijing 100039, China
| | - Wen-Jing Lu
- Department of Laboratory Medicine, The Third Medical Centre of Chinese PLA General Hospital, Beijing 100039, China
| | - Yuan-Yuan Zhang
- Department of Laboratory Medicine, The Third Medical Centre of Chinese PLA General Hospital, Beijing 100039, China
| | - Hua-Guang Wang
- Physiatry Department, Naval Aviation University, Yantai 100071, Shandong Province, China
| | - Yu-Yu Liu
- Department of Organ Transplantation, The Third Medical Centre of Chinese PLA General Hospital, Beijing 100039, China
| | - Shuang Qiu
- Department of Organ Transplantation, The Third Medical Centre of Chinese PLA General Hospital, Beijing 100039, China
| | - Meng Xu
- Department of Organ Transplantation, The Third Medical Centre of Chinese PLA General Hospital, Beijing 100039, China
| | - Zi-Peng Lei
- Department of Organ Transplantation, The Third Medical Centre of Chinese PLA General Hospital, Beijing 100039, China
| | - Qian Zheng
- Department of Organ Transplantation, The Third Medical Centre of Chinese PLA General Hospital, Beijing 100039, China
| | - Xiao-Li Yang
- Department of Laboratory Medicine, The Third Medical Centre of Chinese PLA General Hospital, Beijing 100039, China
| | - Qing Zhang
- Department of Organ Transplantation, The Third Medical Centre of Chinese PLA General Hospital, Beijing 100039, China
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Bansal S, Taddei T, Wells R, Serper M, Bittermann T, Mahmud N, Kaplan DE. Transjugular Intrahepatic Portosystemic Shunt Linked to Increased Risk of Hepatocellular Carcinoma: A VA Matched Cohort Study. J Clin Transl Hepatol 2024; 12:534-538. [PMID: 38779520 PMCID: PMC11106346 DOI: 10.14218/jcth.2023.00554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Revised: 02/01/2024] [Accepted: 02/09/2024] [Indexed: 05/25/2024] Open
Affiliation(s)
- Shalini Bansal
- Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA
| | - Tamar Taddei
- Division of Gastroenterology and Hepatology Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA
| | - Rebecca Wells
- Division of Gastroenterology and Hepatology Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA
| | - Marina Serper
- Division of Gastroenterology and Hepatology Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA
| | - Theresa Bittermann
- Division of Gastroenterology and Hepatology Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA
| | - Nadim Mahmud
- Division of Gastroenterology and Hepatology Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA
- Division of Gastroenterology and Hepatology, Yale University School of Medicine, New Haven, CT, USA
- VA Connecticut Healthcare System, West Haven, CT, USA
| | - David E. Kaplan
- Division of Gastroenterology and Hepatology Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA
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Feuangwattana P, Sripongpun P, Jandee S, Kaewdech A, Chamroonkul N. The Influence of Medical Subspecialty on the Adherence to Hepatocellular Carcinoma Surveillance in Patients with Chronic Hepatitis B. SIRIRAJ MEDICAL JOURNAL 2024; 76:216-224. [DOI: 10.33192/smj.v76i4.266951] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
Objective: This study aimed to determine the adherence rate of HCC surveillance in CHB patients at the largest tertiary hospital in Southern Thailand and identify patient and physician factors that influence it.
Materials and Methods: This retrospective cohort study included patients with CHB who were followed up for more than 1 year between 2011 and 2019 at a tertiary care hospital in Thailand. Patients diagnosed with HCC within 6 months of their first visit were excluded. The rate of adherence with HCC surveillance was calculated using percentage of time up-to-date with HCC surveillance (PTUDS).
Results: The mean age of 531 eligible patients at the time HCC surveillance started was 55.5 ± 9.26 years. The most common indications for surveillance were male over 40 years of age (41.2%), female over 50 years of age (28.9%), and cirrhosis (22.6%). The median PTUDS was 70.6% (interquartile range 55.1 – 81.4%). The highest PTUDS was for cirrhosis (74.0%). For physicians’ subspecialties, the median PTUDS was 71.8% for gastroenterologists (IQR 58.3 – 81.6%) and 41.7% for internists (IQR 31.4 – 65.8%). Factors associated with increased PTUDS by multivariable analysis were having ≥2 clinical visits per year (±18.4%, p<0.001), civil servant reimbursement (±8.81%, p=0.001), cirrhosis (±6.06%, p=0.003), and being follow-up by gastroenterologists (±20.4%, p<0.001).
Conclusion: The adherence with surveillance program in patients with CHB being followed up at a tertiary care setting in Thailand was good. This finding underscores the importance of education regarding indications for HCC surveillance, particularly in patients without cirrhosis.
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Nikzad N, Fuentes DT, Roach M, Chowdhury T, Cagley M, Badawy M, Elkhesen A, Hassan M, Elsayes KM, Beretta L, Koay EJ, Jalal PK. Enhancement Pattern Mapping for Early Detection of Hepatocellular Carcinoma in Patients with Cirrhosis. J Hepatocell Carcinoma 2024; 11:595-606. [PMID: 38525156 PMCID: PMC10961013 DOI: 10.2147/jhc.s449996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Accepted: 03/07/2024] [Indexed: 03/26/2024] Open
Abstract
Background and Aims Limited methods exist to accurately characterize the risk of malignant progression of liver lesions. Enhancement pattern mapping (EPM) measures voxel-based root mean square deviation (RMSD) of parenchyma and the contrast-to-noise (CNR) ratio enhances in malignant lesions. This study investigates the utilization of EPM to differentiate between HCC versus cirrhotic parenchyma with and without benign lesions. Methods Patients with cirrhosis undergoing MRI surveillance were studied prospectively. Cases (n=48) were defined as patients with LI-RADS 3 and 4 lesions who developed HCC during surveillance. Controls (n=99) were patients with and without LI-RADS 3 and 4 lesions who did not develop HCC. Manual and automated EPM signals of liver parenchyma between cases and controls were quantitatively validated on an independent patient set using cross validation with manual methods avoiding parenchyma with artifacts or blood vessels. Results With manual EPM, RMSD of 0.37 was identified as a cutoff for distinguishing lesions that progress to HCC from background parenchyma with and without lesions on pre-diagnostic scans (median time interval 6.8 months) with an area under the curve (AUC) of 0.83 (CI: 0.73-0.94) and a sensitivity, specificity, and accuracy of 0.65, 0.97, and 0.89, respectively. At the time of diagnostic scans, a sensitivity, specificity, and accuracy of 0.79, 0.93, and 0.88 were achieved with manual EPM with an AUC of 0.89 (CI: 0.82-0.96). EPM RMSD signals of background parenchyma that did not progress to HCC in cases and controls were similar (case EPM: 0.22 ± 0.08, control EPM: 0.22 ± 0.09, p=0.8). Automated EPM produced similar quantitative results and performance. Conclusion With manual EPM, a cutoff of 0.37 identifies quantifiable differences between HCC cases and controls approximately six months prior to diagnosis of HCC with an accuracy of 89%.
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Affiliation(s)
- Newsha Nikzad
- Department of Medicine and Surgery, Baylor College of Medicine, Houston, TX, USA
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Department of Internal Medicine, The University of Chicago Medical Center, Chicago, IL, USA
| | - David Thomas Fuentes
- Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Millicent Roach
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Tasadduk Chowdhury
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Matthew Cagley
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Mohamed Badawy
- Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ahmed Elkhesen
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA
| | - Manal Hassan
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Khaled M Elsayes
- Department of Abdominal Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Laura Beretta
- Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Eugene Jon Koay
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Prasun Kumar Jalal
- Department of Medicine and Surgery, Baylor College of Medicine, Houston, TX, USA
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11
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Johnson PJ, Bhatti E, Toyoda H, He S. Serologic Detection of Hepatocellular Carcinoma: Application of Machine Learning and Implications for Diagnostic Models. JCO Clin Cancer Inform 2024; 8:e2300199. [PMID: 38513163 DOI: 10.1200/cci.23.00199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Revised: 12/11/2023] [Accepted: 02/06/2024] [Indexed: 03/23/2024] Open
Abstract
PURPOSE The gender, age, lens culinaris agglutinin-reactive fraction of alphafetoprotein, alphafetoprotein, des-gamma-carboxyprothrombin (GALAD) score is a biomarker-based statistical model for the serologic diagnosis of hepatocellular carcinoma (HCC) that has been developed and validated using the case-control approach with a view to early detection. Performance has, however, been suboptimal in the first prospective studies which better reflect the real-world situation. In this article, we report the application of machine learning to a large, prospectively accrued, HCC surveillance data set. PATIENTS AND METHODS Models were built on a cohort of 3,473 patients with chronic liver disease within a rigorous surveillance program between 1998 and 2014, during which 459 patients with HCC were detected. Two random forest (RF) models were trained. The first RF model uses the same variables as the original GALAD model (GALAD-RF); the second is based on routinely available clinical and laboratory features (RF-practical). For comparison, we evaluated a logistic regression GALAD model trained on this longitudinal prospective data set (termed GALAD-Ogaki). RESULTS Models were evaluated using a repetitive cross-validation approach with the metrics averaged over 100 independent runs. As judged by area under the receiver operator curve (AUROC) and F1 score, the GALAD RF model significantly outperformed the original GALAD model. The RF-practical model also outperformed the original GALAD model in terms of both AUROC and F1 score, and both models outperformed the individual biomarkers. An online web application that implemented the GALAD-RF and RF-practical models is presented. CONCLUSION RF-based models improve on the diagnostic performance of the original GALAD model in the setting of a standard HCC surveillance program. Further prospective validation studies are warranted using these models and could be expanded to offer prediction of risk of HCC development over defined periods of time.
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Affiliation(s)
- Philip J Johnson
- Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, United Kingdom
| | - Ehsan Bhatti
- School of Computer Science, University of Birmingham, Birmingham, United Kingdom
| | - Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Shan He
- School of Computer Science, University of Birmingham, Birmingham, United Kingdom
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12
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Chu JN, Goldman ML, Brandman D, Sohn JH, Islam K, Ross LA, Fox RK. Underrecognition and Suboptimal Quality of Care for Nonalcoholic Fatty Liver Disease Cirrhosis in Primary Care Patients with Diabetes Mellitus. Am J Med 2024; 137:172-177.e2. [PMID: 37890572 DOI: 10.1016/j.amjmed.2023.10.002] [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: 05/12/2023] [Revised: 10/10/2023] [Accepted: 10/11/2023] [Indexed: 10/29/2023]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a leading cause of cirrhosis but is underrecognized in primary care. Cirrhosis management requires complex monitoring, and the quality of care (QoC) for NAFLD cirrhosis patients in primary care may be inadequate. METHODS In this retrospective-prospective cohort study of primary care patients with diabetes mellitus, we identified patients with NAFLD cirrhosis by 1) evidence of cirrhosis from abdominal imaging identified by natural language processing, or 2) existence of International Classification of Diseases code for cirrhosis. A finding of either was followed by manual chart review for confirmation of both cirrhosis and NAFLD. We then determined if cirrhosis care measures were up-to-date, including hepatitis A and B vaccination, Model for End-Stage Liver Disease score components, esophagogastroduodenoscopy, and hepatocellular carcinoma screening. We created a composite score quantifying overall QoC (scale 0-8), with high QoC defined as ≥6 points. RESULTS Among 3,028 primary care patients with diabetes mellitus, we identified 51 (1.7%) with NAFLD cirrhosis. Although 78% had ≥3 average primary care visits/year, only 24% completed hepatocellular carcinoma screening at least annually in at least 75% of years since diagnosis. The average QoC composite score was 4.9 (SD 2.4), and less than one-third had high QoC. CONCLUSIONS NAFLD cirrhosis is prevalent but underdiagnosed in primary care, and receipt of comprehensive QoC was suboptimal. Given the rising incidence of NAFLD cirrhosis, primary care providers need improved awareness and mechanisms to ensure high QoC for this population.
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Affiliation(s)
- Janet N Chu
- Division of General Internal Medicine, Department of Medicine, University of California, San Francisco, CA
| | - Max L Goldman
- Division of Hospital Medicine, Department of Medicine, San Francisco Veterans Affairs Medical Center and University of California, San Francisco, CA; Department of Gastroenterology, Kaiser Permanente San Francisco, CA
| | - Danielle Brandman
- Center for Liver Disease and Transplantation, Weill Cornell Medicine, New York, NY
| | - Jae Ho Sohn
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA
| | - Kendall Islam
- School of Medicine, University of California, San Francisco, CA
| | - Lauren A Ross
- Department of Psychological and Brain Sciences, Dartmouth College, Hanover, NH
| | - Rena K Fox
- Division of General Internal Medicine, Department of Medicine, University of California, San Francisco, CA.
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13
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Ufere NN, Lago-Hernandez C, Alejandro-Soto A, Walker T, Li L, Schoener K, Keegan E, Gonzalez C, Bethea E, Singh S, El-Jawahri A, Nephew L, Jones P, Serper M. Health care-related transportation insecurity is associated with adverse health outcomes among adults with chronic liver disease. Hepatol Commun 2024; 8:e0358. [PMID: 38206200 PMCID: PMC10786597 DOI: 10.1097/hc9.0000000000000358] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 11/07/2023] [Indexed: 01/12/2024] Open
Abstract
BACKGROUND Health care-related transportation insecurity (delayed or forgone medical care due to transportation barriers) is being increasingly recognized as a social risk factor affecting health outcomes. We estimated the national burden and adverse outcomes of health care-related transportation insecurity among US adults with chronic liver disease (CLD). METHODS Using the U.S. National Health Interview Survey from 2014 to 2018, we identified adults with self-reported CLD. We used complex weighted survey analysis to obtain national estimates of health care-related transportation insecurity. We examined the associations between health care-related transportation insecurity and health care-related financial insecurity, food insecurity, self-reported health status, work productivity, health care use, and mortality. RESULTS Of the 3643 (representing 5.2 million) US adults with CLD, 267 [representing 307,628 (6%; 95% CI: 5%-7%)] reported health care-related transportation insecurity. Adults with CLD experiencing health care-related transportation insecurity had 3.5 times higher odds of cost-related medication nonadherence [aOR, 3.5; (2.4-5.0)], 3.5 times higher odds of food insecurity [aOR, 3.5; (2.4-5.3)], 2.5 times higher odds of worsening self-reported health status over the past year [aOR, 2.5; (1.7-3.7)], 3.1 times higher odds of being unable to work due to poor health over the past year [aOR, 3.1; (2.0-4.9)], and 1.7 times higher odds of being in a higher-risk category group for number of hospitalizations annually [aOR, 1.7; (1.2-2.5)]. Health care-related transportation insecurity was independently associated with mortality after controlling for age, income, insurance status, comorbidity burden, financial insecurity, and food insecurity [aHR, 1.7; (1.4-2.0)]. CONCLUSIONS Health care-related transportation insecurity is a critical social risk factor that is associated with health care-related financial insecurity, food insecurity, poorer self-reported health status and work productivity, and increased health care use and mortality among US adults with CLD. Efforts to screen for and reduce health care-related transportation insecurity are warranted.
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Affiliation(s)
- Nneka N. Ufere
- Liver Center, Gastrointestinal Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Carlos Lago-Hernandez
- Department of Medicine, Division of Hospital Medicine, University of California San Diego, La Jolla, California, USA
| | - Alysa Alejandro-Soto
- Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Tiana Walker
- Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Lucinda Li
- Liver Center, Gastrointestinal Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Kimberly Schoener
- Department of Social Services, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Eileen Keegan
- Department of Social Services, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Carolina Gonzalez
- Department of Social Services, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Emily Bethea
- Liver Center, Gastrointestinal Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Siddharth Singh
- Department of Medicine, Division of Gastroenterology and Hepatology, University of California San Diego, La Jolla, California, USA
- Department of Medicine, Division of Biomedical Informatics, University of California San Diego, La Jolla, California, USA
| | - Areej El-Jawahri
- Division of Hematology and Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Lauren Nephew
- Division of Gastroenterology & Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Patricia Jones
- Department of Medicine, Division of Digestive Health and Liver Services, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Marina Serper
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
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14
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Mehta SJ, McDonald C, Reitz C, Kastuar S, Snider CK, Okorie E, McNelis K, Shaikh H, Cook TS, Goldberg DS, Rothstein K. A randomized trial of mailed outreach with behavioral economic interventions to improve liver cancer surveillance. Hepatol Commun 2024; 8:e0349. [PMID: 38099859 PMCID: PMC10727671 DOI: 10.1097/hc9.0000000000000349] [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: 09/22/2023] [Accepted: 11/08/2023] [Indexed: 12/18/2023] Open
Abstract
BACKGROUND Surveillance rates for HCC remain limited in patients with cirrhosis. We evaluated whether opt-out mailed outreach increased uptake with or without a $20 unconditional incentive. METHODS This was a pragmatic randomized controlled trial in an urban academic health system including adult patients with cirrhosis or advanced fibrosis, at least 1 visit to a specialty practice in the past 2 years and no surveillance in the last 7 months. Patients were randomized in a 1:2:2 ratio to (1) usual care, (2) a mailed letter with a signed order for an ultrasound, or (3) a mailed letter with an order and a $20 unconditional incentive. The main outcome was the proportion with completion of ultrasound within 6 months. RESULTS Among the 562 patients included, the mean age was 62.1 (SD 11.1); 56.8% were male, 51.1% had Medicare, and 40.6% were Black. At 6 months, 27.6% (95% CI: 19.5-35.7) completed ultrasound in the Usual care arm, 54.5% (95% CI: 47.9-61.0) in the Letter + Order arm, and 54.1% (95% CI: 47.5-60.6) in the Letter + Order + Incentive arm. There was a significant increase in the Letter + Order arm compared to Usual care (absolute difference of 26.9%; 95% CI: 16.5-37.3; p<0.001), but no significant increase in the Letter + Order + Incentive arm compared to Letter + Order (absolute difference of -0.4; 95% CI: -9.7 to 8.8; p=0.93). CONCLUSIONS There was an increase in HCC surveillance from mailed outreach with opt-out framing and a signed order slip, but no increase in response to the financial incentive.
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Affiliation(s)
- Shivan J. Mehta
- Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA
- Center for Health Care Innovation, University of Pennsylvania, Philadelphia, USA
| | - Caitlin McDonald
- Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA
- Center for Health Care Innovation, University of Pennsylvania, Philadelphia, USA
| | - Catherine Reitz
- Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA
- Center for Health Care Innovation, University of Pennsylvania, Philadelphia, USA
| | - Shivani Kastuar
- Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA
| | | | - Evelyn Okorie
- Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA
- Center for Health Care Innovation, University of Pennsylvania, Philadelphia, USA
| | - Kiernan McNelis
- Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA
- Center for Health Care Innovation, University of Pennsylvania, Philadelphia, USA
| | - Hamzah Shaikh
- Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA
| | - Tessa S. Cook
- Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA
| | - David S. Goldberg
- Department of Medicine, Miller School of Medicine, University of Miami, Miami, Florida, USA
| | - Kenneth Rothstein
- Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA
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15
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Chen J, Gao G, He Y, Zhang Y, Wu H, Dai P, Zheng Q, Huang H, Weng J, Zheng Y, Huang Y. Construction and validation of a novel lysosomal signature for hepatocellular carcinoma prognosis, diagnosis, and therapeutic decision-making. Sci Rep 2023; 13:22624. [PMID: 38114725 PMCID: PMC10730614 DOI: 10.1038/s41598-023-49985-3] [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: 09/11/2023] [Accepted: 12/14/2023] [Indexed: 12/21/2023] Open
Abstract
Lysosomes is a well-recognized oncogenic driver and chemoresistance across variable cancer types, and has been associated with tumor invasiveness, metastasis, and poor prognosis. However, the significance of lysosomes in hepatocellular carcinoma (HCC) is not well understood. Lysosomes-related genes (LRGs) were downloaded from Genome Enrichment Analysis (GSEA) databases. Lysosome-related risk score (LRRS), including eight LRGs, was constructed via expression difference analysis (DEGs), univariate and LASSO-penalized Cox regression algorithm based on the TCGA cohort, while the ICGC cohort was obtained for signature validation. Based on GSE149614 Single-cell RNA sequencing data, model gene expression and liver tumor niche were further analyzed. Moreover, the functional enrichments, tumor microenvironment (TME), and genomic variation landscape between LRRSlow/LRRShigh subgroup were systematically investigated. A total of 15 Lysosomes-related differentially expressed genes (DELRGs) in HCC were detected, and then 10 prognosis DELRGs were screened out. Finally, the 8 optimal DELRGs (CLN3, GBA, CTSA, BSG, APLN, SORT1, ANXA2, and LAPTM4B) were selected to construct the LRRS prognosis signature of HCC. LRRS was considered as an independent prognostic factor and was associated with advanced clinicopathological features. LRRS also proved to be a potential marker for HCC diagnosis, especially for early-stage HCC. Then, a nomogram integrating the LRRS and clinical parameters was set up displaying great prognostic predictive performance. Moreover, patients with high LRRS showed higher tumor stemness, higher heterogeneity, and higher genomic alteration status than those in the low LRRS group and enriched in metabolism-related pathways, suggesting its underlying role in the progression and development of liver cancer. Meanwhile, the LRRS can affect the proportion of immunosuppressive cell infiltration, making it a vital immunosuppressive factor in the tumor microenvironment. Additionally, HCC patients with low LRRS were more sensitive to immunotherapy, while patients in the high LRRS group responded better to chemotherapy. Upon single-cell RNA sequencing, CLN3, GBA, and LAPTM4B were found to be specially expressed in hepatocytes, where they promoted cell progression. Finally, RT-qPCR and external datasets confirmed the mRNA expression levels of model genes. This study provided a direct links between LRRS signature and clinical characteristics, tumor microenvironment, and clinical drug-response, highlighting the critical role of lysosome in the development and treatment resistance of liver cancer, providing valuable insights into the prognosis prediction and treatment response of HCC, thereby providing valuable insights into prognostic prediction, early diagnosis, and therapeutic response of HCC.
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Affiliation(s)
- Jianlin Chen
- Shengli Clinical Medical College, Fujian Medical University, Fujian, 350001, Fuzhou, China
- Department of Clinical Laboratory, Fujian Provincial Hospital, Fujian, 350001, Fuzhou, China
- Central Laboratory, Fujian Provincial Hospital, Fujian, 350001, Fuzhou, China
- Center for Experimental Research in Clinical Medicine, Fujian Provincial Hospital, Fujian, 350001, Fuzhou, China
| | - Gan Gao
- Department of Clinical Laboratory, Liuzhou Hospital, Guangzhou Women and Children's Medical Center, Liuzhou, 545616, Guangxi, China
- Guangxi Clinical Research Center for Obstetrics and Gynecology, Liuzhou, 545616, Guangxi, China
| | - Yufang He
- Shengli Clinical Medical College, Fujian Medical University, Fujian, 350001, Fuzhou, China
| | - Yi Zhang
- Shengli Clinical Medical College, Fujian Medical University, Fujian, 350001, Fuzhou, China
- Department of Clinical Laboratory, Fujian Provincial Hospital, Fujian, 350001, Fuzhou, China
| | - Haixia Wu
- Shengli Clinical Medical College, Fujian Medical University, Fujian, 350001, Fuzhou, China
| | - Peng Dai
- Department of Anesthesiology, The First People's Hospital of Foshan, Foshan, 528000, Guangdong, China
| | - Qingzhu Zheng
- Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou, 350001, China
| | - Hengbin Huang
- Shengli Clinical Medical College, Fujian Medical University, Fujian, 350001, Fuzhou, China
- Department of Clinical Laboratory, Fujian Provincial Hospital, Fujian, 350001, Fuzhou, China
| | - Jiamiao Weng
- Shengli Clinical Medical College, Fujian Medical University, Fujian, 350001, Fuzhou, China
- Department of Clinical Laboratory, Fujian Provincial Hospital, Fujian, 350001, Fuzhou, China
| | - Yue Zheng
- Shengli Clinical Medical College, Fujian Medical University, Fujian, 350001, Fuzhou, China
- Department of Clinical Laboratory, Fujian Provincial Hospital, Fujian, 350001, Fuzhou, China
| | - Yi Huang
- Shengli Clinical Medical College, Fujian Medical University, Fujian, 350001, Fuzhou, China.
- Department of Clinical Laboratory, Fujian Provincial Hospital, Fujian, 350001, Fuzhou, China.
- Central Laboratory, Fujian Provincial Hospital, Fujian, 350001, Fuzhou, China.
- Center for Experimental Research in Clinical Medicine, Fujian Provincial Hospital, Fujian, 350001, Fuzhou, China.
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16
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Huang DQ, Singal AG, Kanwal F, Lampertico P, Buti M, Sirlin CB, Nguyen MH, Loomba R. Hepatocellular carcinoma surveillance - utilization, barriers and the impact of changing aetiology. Nat Rev Gastroenterol Hepatol 2023; 20:797-809. [PMID: 37537332 DOI: 10.1038/s41575-023-00818-8] [Citation(s) in RCA: 42] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/30/2023] [Indexed: 08/05/2023]
Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. Surveillance for HCC is critical for early detection and treatment, but fewer than one-quarter of individuals at risk of HCC undergo surveillance. Multiple failures across the screening process contribute to the underutilization of surveillance, including limited disease awareness among patients and health-care providers, knowledge gaps, and difficulty recognizing patients who are at risk. Non-alcoholic fatty liver disease and alcohol-associated liver disease are the fastest-rising causes of HCC-related death worldwide and are associated with unique barriers to surveillance. In particular, more than one-third of patients with HCC related to non-alcoholic fatty liver disease do not have cirrhosis and therefore lack a routine indication for HCC surveillance on the basis of current practice guidelines. Semi-annual abdominal ultrasound with measurement of α-fetoprotein levels is recommended for HCC surveillance, but the sensitivity of this approach for early HCC is limited, especially for patients with cirrhosis or obesity. In this Review, we discuss the current status of HCC surveillance and the remaining challenges, including the changing aetiology of liver disease. We also discuss strategies to improve the utilization and quality of surveillance for HCC.
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Affiliation(s)
- Daniel Q Huang
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore.
| | - Amit G Singal
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Fasiha Kanwal
- Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
| | - Pietro Lampertico
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy
- CRC "A. M. and A. Migliavacca" Center for Liver Disease, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Maria Buti
- Liver Unit, Department of Internal Medicine, Hospital Universitari Valle d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
- CIBER-EHD del Instituto Carlos III, Barcelona, Spain
| | - Claude B Sirlin
- Liver Imaging Group, Department of Radiology, UCSD School of Medicine, San Diego, CA, USA
| | - Mindie H Nguyen
- Department of Epidemiology and Population Health, Stanford University Medical Center, Stanford University, Palo Alto, CA, USA
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford University, Palo Alto, CA, USA
| | - Rohit Loomba
- NAFLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, San Diego, CA, USA
- Division of Epidemiology, Department of Family Medicine and Public Health, University of California at San Diego, San Diego, CA, USA
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Elderkin J, Al Hallak N, Azmi AS, Aoun H, Critchfield J, Tobon M, Beal EW. Hepatocellular Carcinoma: Surveillance, Diagnosis, Evaluation and Management. Cancers (Basel) 2023; 15:5118. [PMID: 37958294 PMCID: PMC10647678 DOI: 10.3390/cancers15215118] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Revised: 10/11/2023] [Accepted: 10/13/2023] [Indexed: 11/15/2023] Open
Abstract
Hepatocellular carcinoma (HCC) ranks fourth in cancer-related deaths worldwide. Semiannual surveillance of the disease for patients with cirrhosis or hepatitis B virus allows for early detection with more favorable outcomes. The current underuse of surveillance programs demonstrates the need for intervention at both the patient and provider level. Mail outreach along with navigation provision has proven to increase surveillance follow-up in patients, while provider-targeted electronic medical record reminders and compliance reports have increased provider awareness of HCC surveillance. Imaging is the primary mode of diagnosis in HCC with The Liver Imaging Reporting and Data System (LI-RADS) being a widely accepted comprehensive system that standardizes the reporting and data collection for HCC. The management of HCC is complex and requires multidisciplinary team evaluation of each patient based on their preference, the state of the disease, and the available medical and surgical interventions. Staging systems are useful in determining the appropriate intervention for HCC. Early-stage HCC is best managed by curative treatment modalities, such as liver resection, transplant, or ablation. For intermediate stages of the disease, transarterial local regional therapies can be applied. Advanced stages of the disease are treated with systemic therapies, for which there have been recent advances with new drug combinations. Previously sorafenib was the mainstay systemic treatment, but the recent introduction of atezolizumab plus bevacizumab proves to have a greater impact on overall survival. Although there is a current lack of improved outcomes in Phase III trials, neoadjuvant therapies are a potential avenue for HCC management in the future.
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Affiliation(s)
- Jessica Elderkin
- Wayne State University School of Medicine, Detroit, MI 48201, USA;
| | - Najeeb Al Hallak
- Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA; (N.A.H.); (A.S.A.)
| | - Asfar S. Azmi
- Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA; (N.A.H.); (A.S.A.)
| | - Hussein Aoun
- Department of Radiology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA; (H.A.); (J.C.)
| | - Jeffrey Critchfield
- Department of Radiology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA; (H.A.); (J.C.)
| | - Miguel Tobon
- Department of Surgery, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA;
| | - Eliza W. Beal
- Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA; (N.A.H.); (A.S.A.)
- Department of Surgery, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA;
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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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An S, Zhan X, Liu M, Li L, Wu J. Diagnostic and Prognostic Nomograms for Hepatocellular Carcinoma Based on PIVKA-II and Serum Biomarkers. Diagnostics (Basel) 2023; 13:diagnostics13081442. [PMID: 37189543 DOI: 10.3390/diagnostics13081442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 04/06/2023] [Accepted: 04/07/2023] [Indexed: 05/17/2023] Open
Abstract
BACKGROUND The aim of the present study was to develop an improved diagnostic and prognostic model for HBV-associated HCC by combining AFP with PIVKA-II and other potential serum/plasma protein biomarkers. METHODS A total of 578 patients, including 352 patients with HBV-related HCC, 102 patients with HBV-associated liver cirrhosis (LC), 124 patients with chronic HBV, and 127 healthy subjects (HS), were enrolled in the study. The serum levels of AFP, PIVKA-II, and other laboratory parameters were collected. Univariate and multivariate logistic regression and Cox regression analyses were performed to identify independent diagnostic and prognostic factors, respectively. The diagnostic efficacy of the nomogram was evaluated using receiver operator curve (ROC) analysis and the prognostic performance was measured by Harrell's concordance index (C-index). RESULTS AFP and PIVKA-II levels were significantly increased in HBV-related HCC, compared with those in HBV-associated LC and chronic HBV participants (p < 0.05 and p < 0.001, respectively). The diagnostic nomogram, which included age, gender, AFP, PIVKA-II, prothrombin time (PT), and total protein (TP), discriminated patients with HBV-HCC from those with HBV-LC or chronic HBV with an AUC of 0.970. In addition, based on the univariate and multivariate Cox regression analysis, PIVKA-II, γ-glutamyl transpeptidase, and albumin were found to be significantly associated with the prognosis of HBV-related HCC and were incorporated into a nomogram. The C-index of the nomogram for predicting 3-year survival in the training and validation groups was 0.75 and 0.78, respectively. The calibration curves for the probability of 3-year OS showed good agreement between the nomogram prediction and the actual observation in the training and the validation groups. Furthermore, the nomogram had a higher C-index (0.74) than that of the Child-Pugh grade (0.62), the albumin-bilirubin (ALBI) score (0.64), and Barcelona Clinic Liver Cancer (0.56) in all follow-up cases. CONCLUSION Our study suggests that the nomograms based on AFP, PIVKA-II, and potential serum protein biomarkers showed a better performance in the diagnosis and prognosis of HCC, which may help to guide therapeutic strategies and assess the prognosis of HCC.
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Affiliation(s)
- Shu An
- Department of Laboratory Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
| | - Xiaoxia Zhan
- Department of Laboratory Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
| | - Min Liu
- Department of Laboratory Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
| | - Laisheng Li
- Department of Laboratory Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
| | - Jian Wu
- Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
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20
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King WW, Richhart R, Culpepper T, Mota M, Banerjee D, Ismael M, Chakraborty J, Ladna M, Khan W, Ruiz N, Wilson J, Altshuler E, Clark V, Cabrera R. Adherence to guideline-directed hepatocellular carcinoma screening: A single-center US experience. World J Hepatol 2023; 15:410-418. [PMID: 37034234 PMCID: PMC10075011 DOI: 10.4254/wjh.v15.i3.410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Revised: 01/16/2023] [Accepted: 02/21/2023] [Indexed: 03/22/2023] Open
Abstract
BACKGROUND The American Association for the Study of Liver Disease recommends screening patients with cirrhosis for hepatocellular carcinoma (HCC) using imaging with or without alpha-fetoprotein every six months. Unfortunately, screening rates remain inadequate.
AIM To assess root causes of screening failure in a subspecialty hepatology clinic.
METHODS The authors identified patients with cirrhosis seen in a subspecialty hepatology clinic and determined whether they underwent appropriate screening, defined as two cross-sectional images between five and seven months apart. The authors characterized the primary driver of screening failure. Finally, other hepatologists were surveyed to determine provider perceptions of screening failure causes.
RESULTS 1034 patients were identified with an average age of 61 years and a mean MELD of 8.1 ± 3.8. Hepatitis C virus was the most common cirrhosis etiology. 489 (47%) underwent appropriate screening. No demographic or clinical differences were detected between those who underwent appropriate screening and those who did not. The most common etiologies of screening failure, in descending order, were: radiology unable to schedule timely imaging, provider did not order imaging, patient canceled follow up appointment, appointments scheduled too far apart, lost to follow up, no-show to radiology appointment, and provider canceled appointment. Hepatologists surveyed believed the most common cause of screening failure was no-show to radiology.
CONCLUSION Rates of screening were poor even in a subspecialty hepatology clinic. Screening failure was mostly due to systemic factors such as radiology availability and time between hepatology appointments rather than individual error.
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Affiliation(s)
- William W King
- Department of Medicine, University of Florida, Gainesville, FL 32610, United States
| | - Raymond Richhart
- Department of Medicine, University of Florida, Gainesville, FL 32610, United States
| | - Tyler Culpepper
- Department of Medicine, University of Florida, Gainesville, FL 32610, United States
| | - Maneola Mota
- Department of Gastroenterology, University of Florida, Gainesville, FL 32610, United States
| | - Debdeep Banerjee
- Department of Medicine, University of Florida, Gainesville, FL 32610, United States
| | - Media Ismael
- Department of Gastroenterology, University of Florida, Gainesville, FL 32610, United States
| | - Joydeep Chakraborty
- Department of Gastroenterology, University of Florida, Gainesville, FL 32610, United States
| | - Michael Ladna
- Department of Hospital Medicine, University of Florida, Gainesville, FL 32610, United States
| | - Walid Khan
- Department of Hospital Medicine, University of Florida, Gainesville, FL 32610, United States
| | - Nicole Ruiz
- Department of Medicine, University of Florida, Gainesville, FL 32610, United States
| | - Jake Wilson
- Department of Medicine, University of Florida, Gainesville, FL 32610, United States
| | - Ellery Altshuler
- Department of Medicine, University of Florida, Gainesville, FL 32610, United States
| | - Virginia Clark
- Department of Gastroenterology, University of Florida, Gainesville, FL 32610, United States
| | - Roniel Cabrera
- Department of Gastroenterology, University of Florida, Gainesville, FL 32610, United States
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HAMP as a Potential Diagnostic, PD-(L)1 Immunotherapy Sensitivity and Prognostic Biomarker in Hepatocellular Carcinoma. Biomolecules 2023; 13:biom13020360. [PMID: 36830729 PMCID: PMC9953231 DOI: 10.3390/biom13020360] [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: 11/08/2022] [Revised: 12/09/2022] [Accepted: 12/14/2022] [Indexed: 02/16/2023] Open
Abstract
Hepatocellular carcinoma (HCC) remains a global medical problem. Programmed cell death protein 1 (PD-1) is a powerful weapon against many cancers, but it is not sensitive to some patients with HCC. We obtained datasets from the Gene Expression Omnibus (GEO) database on HCC patients and PD-1 immunotherapy to select seven intersecting DEGs. Through Lasso regression, two intersecting genes were acquired as predictors of HCC and PD-1 treatment prognosis, including HAMP and FOS. Logistic regression was performed to build a prediction model. HAMP had a better ability to diagnose HCC and predict PD1 treatment sensitivity. Further, we adapted the support vector machine (SVM) technique using HAMP to predict triple-classified outcomes after PD1 treatment in HCC patients, which had an excellent classification ability. We also performed external validation using TCGA data, which showed that HAMP was elevated in the early stage of HCC. HAMP was positively correlated with the infiltration of 18 major immune cells and the expression of 2 important immune checkpoints, PDCD1 and CTLA4. We discovered a biomarker that can be used for the early diagnosis, prognosis and PD1 immunotherapy efficacy prediction of HCC for the first time and developed a diagnostic model, prognostic model and prediction model of PD1 treatment sensitivity and treatment outcome for HCC patients accordingly.
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Serper M, Tapper EB, Kaplan DE, Taddei TH, Mahmud N. Patterns of Care Utilization and Hepatocellular Carcinoma Surveillance: Tracking Care Across the Pandemic. Am J Gastroenterol 2023; 118:294-303. [PMID: 36114778 PMCID: PMC9898115 DOI: 10.14309/ajg.0000000000002011] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Accepted: 09/09/2022] [Indexed: 02/06/2023]
Abstract
INTRODUCTION We studied longitudinal trends in mortality, outpatient, and inpatient care for cirrhosis in a national cohort in the first 2 years of the coronavirus disease-2019 pandemic. We evaluated trends in hepatocellular carcinoma (HCC) surveillance and factors associated with completion. METHODS Within the national cirrhosis cohort in the Veterans Administration from 2020 to 2021, we captured mortality, outpatient primary care provider, gastroenterology/hepatology (GI/HEP) visits, and hospitalizations. HCC surveillance was computed as percentage of time up to date with surveillance every 6 months (PTUDS). Multivariable models for PTUDS were adjusted for patient demographics, clinical factors, and facility-level variables. RESULTS The total cohort was 68,073; 28,678 were eligible for HCC surveillance. Outpatient primary care provider and GI/HEP appointment rates initially dropped from 30% to 7% with a rebound 1 year into the pandemic and steady subsequent use. Telemedicine monthly visit rates rose from less than 10% to a peak of 20% with a steady gradual decline. Nearly 70% of Veterans were up to date with HCC surveillance before the pandemic with an early pandemic nadir of approximately 50% and 60% PTUDS 2 years into the pandemic. In adjusted models, use of a population-based cirrhosis dashboard (β 8.5, 95% CI 6.9-10.2) and GI/HEP visits both in-person (β 3.2, 95% CI 2.9-3.6) and telemedicine (β 2.1, 95% CI 1.9-2.4) were associated with a higher PTUDS. DISCUSSION Outpatient utilization and HCC surveillance rates have rebounded but remain below at baseline. Population-based approaches and specialty care for cirrhosis were associated with a higher completion of HCC surveillance.
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Affiliation(s)
- Marina Serper
- Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
- Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, PA
- Department of Medicine, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
| | - Elliot B. Tapper
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, USA
- Gastroenterology Section, Ann Arbor Healthcare System, Ann Arbor, VA, USA
| | - David E Kaplan
- Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
- Department of Medicine, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
| | - Tamar H. Taddei
- Section of Digestive Diseases, Yale School of Medicine, New Haven, CT
- VA Connecticut Healthcare System, West Haven, CT
| | - Nadim Mahmud
- Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
- Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, PA
- Department of Medicine, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
- Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics, Epidemiology & Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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23
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Utilization of Hepatocellular Carcinoma Surveillance Programs in Patients With Cirrhosis: A Systematic Review and Meta-Analysis. J Clin Gastroenterol 2023; 57:198-203. [PMID: 34999648 DOI: 10.1097/mcg.0000000000001668] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 11/06/2021] [Indexed: 01/07/2023]
Abstract
Patients with cirrhosis are advised to undergo hepatocellular carcinoma (HCC) surveillance every 6 months. Routine surveillance is associated with early tumor detection and improved survival. However, surveillance is underutilized. We aimed to characterize the uptake of HCC surveillance in cirrhotic patients following the implementation of interventional programs. We performed a comprehensive literature search of major databases (from inception to October 2020). Surveillance was defined as having an abdominal sonogram every 6 months. Nine studies were included for meta-analysis which involved 4550 patients. The etiology of liver cirrhosis was largely due to hepatitis C or B (n=2023), followed by alcohol (n=857), and nonalcoholic steatohepatitis (n=432). Patients enrolled in surveillance programs were 6 times more likely to undergo abdominal sonography when compared with standard of care (odds ratio=6.00; 95% confidence interval: 3.35-10.77). On subgroup analysis, clinical reminders were associated with a 4 times higher rate of HCC surveillance compared with standard of care (odds ratio=3.80; 95% confidence interval: 2.25-6.39). Interventional programs significantly improve the rate of HCC surveillance. This is clinically impactful and should be considered as a means for improving surveillance rates.
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24
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Parikh ND, Tayob N, Singal AG. Blood-based biomarkers for hepatocellular carcinoma screening: Approaching the end of the ultrasound era? J Hepatol 2023; 78:207-216. [PMID: 36089157 PMCID: PMC10229257 DOI: 10.1016/j.jhep.2022.08.036] [Citation(s) in RCA: 61] [Impact Index Per Article: 30.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Revised: 08/23/2022] [Accepted: 08/29/2022] [Indexed: 02/01/2023]
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, in part because of inadequate early detection strategies. Current recommendations for screening consist of semi-annual abdominal ultrasound with or without serum alpha-fetoprotein in patients with cirrhosis and in demographic subgroups with chronic hepatitis B infection. However, this screening strategy has several deficiencies, including suboptimal early-stage sensitivity, false positives with subsequent harms, inter-operator variability in ultrasound performance, and poor adherence. A blood-based biomarker with sufficient performance characteristics for early-stage disease could overcome several of these barriers to improving early-stage detection. However, prior to use of a biomarker for screening in clinical practice, a multistep validation is required in order to understand test performance characteristics. These steps include case-control validation, followed by validation in prospective cohorts of at-risk patients. Until recently, we lacked adequate longitudinal validation cohorts for early HCC detection; however, several validation cohorts are maturing, including the Hepatocellular Carcinoma Early Detection Study and the Texas Hepatocellular Carcinoma Consortium, which will allow for rigorous validation of candidate biomarkers. While there are several promising biomarkers awaiting validation, in order to supplant abdominal ultrasound, a candidate biomarker must show adequate test performance and overcome practical hurdles to ensure adoption in clinical practice. The promise of blood-based biomarkers is significant, especially given the limitations of ultrasound-based screening; however, they require adequate validation and several logistical obstacles must be overcome prior to clinical implementation.
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Affiliation(s)
- Neehar D Parikh
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
| | - Nabihah Tayob
- Department of Biostatistics, Dana Farber Cancer Center, Boston, MA, USA
| | - Amit G Singal
- Harold C. Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA
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25
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Nguyen MH, Roberts LR, Engel-Nitz NM, Bancroft T, Ozbay AB, Singal AG. Gaps in hepatocellular carcinoma surveillance in a United States cohort of insured patients with cirrhosis. Curr Med Res Opin 2022; 38:2163-2173. [PMID: 36111416 DOI: 10.1080/03007995.2022.2124070] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
OBJECTIVE Surveillance for hepatocellular carcinoma (HCC) is known to be underutilized; however, neither the variation of surveillance adherence by cirrhosis etiology nor the patient-side economic burden of surveillance are well understood. To identify potential barriers to HCC surveillance, we assessed utilization patterns and costs among US patients with cirrhosis monitored in routine clinical practice. METHODS We conducted a retrospective study of insured adult patients with cirrhosis using national administrative claims data from January 2013 through June 2019. Time up-to-date with recommended surveillance, correlates of surveillance receipt, and surveillance-associated costs were assessed during a ≥ 6-month follow-up. RESULTS Among 15,543 patients with cirrhosis (mean [SD] age 64.0 [11.1] years, 50.7% male), 45.8% and 58.7% had received any abdominal imaging at 6 and 12 months, respectively. Patients were up-to-date with recommended surveillance for only 31% of a median 1.3-year follow-up. Those with viral hepatitis were more likely to receive surveillance than those with other etiologies (hazard ratio [HR] 1.55, 95% CI 1.11-2.17, p = .010 for patients without a baseline gastroenterologist [GI] visit and 2.69, 95% CI 1.77-4.09, p < .001 for patients with a GI visit, relative to those with nonalcoholic fatty liver disease and no GI visit). For all etiologies except NAFLD, the HR (95% CI) for surveillance receipt was higher among patients with vs without a baseline GI visit (alcohol-related, 1.164 [1.002-1.351] vs 0.880 [0.796-0.972]; viral hepatitis, 2.688 [1.765-4.093] vs 1.553 [1.111-2.171]; Other, 0.612 [0.519-0.722] vs 0.549 [0.470-0.641]). Mean total and patient-paid daily surveillance-related costs ranged from $540 and $113, respectively (ultrasound) to $1580 and $300, respectively (magnetic resonance imaging), and mean estimated patient productivity costs were $730-$2514 annually. CONCLUSION HCC surveillance was underutilized and was lowest among patients with nonviral etiologies and those who had not seen a gastroenterologist. Surveillance-related out-of-pocket expenses and lost productivity were substantial. The development of surveillance strategies that reduce patient burden, such as those using blood-based biomarkers, may help improve surveillance adherence and effectiveness.
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Affiliation(s)
- Mindie H Nguyen
- Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
- Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, CA, USA
| | | | | | | | | | - Amit G Singal
- UT Southwestern Medical Center, Dallas, TX, USA
- North American Liver Cancer Consortium
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26
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Wong RJ, Jayasekera C, Jones P, Kanwal F, Singal AG, Ahmed A, Taglienti R, Younossi Z, Kulik L, Mehta N. An Open-Access, Interactive Decision-Support Tool to Facilitate Guideline-Driven Care for Hepatocellular Carcinoma. Gastroenterology Res 2022; 15:297-307. [PMID: 36660470 PMCID: PMC9822660 DOI: 10.14740/gr1573] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Accepted: 11/07/2022] [Indexed: 12/23/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is increasing in incidence and is a leading cause of cancer-related mortality worldwide. Adherence to HCC surveillance guidelines and appropriate treatment triage of liver lesions may improve receipt of curative-intent treatment and improved survival. Late-stage HCC diagnosis reflects sub-optimal implementation of effective HCC surveillance, whereas inappropriate treatment triage or linkage to care accounts for the non-receipt of curative-intent in close to half of early-stage HCC in the USA. A free, open-access decision-support tool for liver lesions that incorporates current guideline recommendations in a user-friendly interface could improve appropriate and timely triage of patients to appropriate care. This review provides a summary of gaps and disparities in linkage to HCC care and introduces a free, internet-based, interactive decision-support tool for managing liver lesions. This tool has been developed by the HCC Steering Committee of the Chronic Liver Disease Foundation and is targeted toward clinicians across specialties who may encounter liver lesions during routine care or as part of dedicated HCC surveillance.
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Affiliation(s)
- Robert J. Wong
- Veterans Affairs Palo Alto Healthcare System, Stanford University School of Medicine, Palo Alto, CA, USA,Corresponding Author: Robert J. Wong, Veterans Affairs Palo Alto Healthcare System, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
| | | | | | - Fasiha Kanwal
- Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX, USA
| | - Amit G. Singal
- University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Aijaz Ahmed
- Stanford University School of Medicine, Stanford, CA, USA
| | | | | | | | - Neil Mehta
- University of California, San Francisco, CA, USA
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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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28
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Evaluation of the aMAP score for hepatocellular carcinoma surveillance: a realistic opportunity to risk stratify. Br J Cancer 2022; 127:1263-1269. [PMID: 35798825 PMCID: PMC9519948 DOI: 10.1038/s41416-022-01851-1] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 04/13/2022] [Accepted: 05/09/2022] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND AND AIMS The aMAP score is a model that predicts risk of hepatocellular carcinoma (HCC) development in patients with chronic hepatitis. Its performance in a 'real world' surveillance setting has not yet been ascertained. PATIENTS AND METHODS We had access to a cohort of 3473 individuals enrolled in a rigorously implemented and prospectively accrued surveillance programme (patients undergoing regular ultrasound and biomarker examination between 1998 and 2021). During this period 445 had HCC detected. Of these, 77.8% had early stage disease (within Milan criteria), permitting potentially curative therapy to be implemented in nearly 70% of cases. We applied the recently developed aMAP score to classify patients according to their initial aMAP score in to low, medium and high-risk groups as proposed in the original publication. The performance of the aMAP score was assessed according to the concordance-index and calibration (i.e. agreement between observed and predicted risk). Allowance was made for competing causes of death. RESULTS The aMAP score achieved an overall C-index of 0.81 (95% CI: 0.79-0.82) consistent with the initial report and was unaffected by allowance for competing causes of death. Sub-group analysis showed that the results did not change significantly according to gender, or aetiology. However, aMAP discrimination was greater for younger individuals (versus older individuals), and also for individuals without cirrhosis. The HCC incidence rate was 0.98, 7.05 and 29.1 events per 1000 person-years in the low-, moderate- and high-risk aMAP groups, respectively. CONCLUSIONS The results from this 'real-world' cohort demonstrate that risk stratification is a realistic prospect and that identification of a subgroup of chronic liver disease patients who have a very low risk of HCC is feasible.
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Nguyen MH, Roberts LR, Engel‐Nitz NM, Bancroft T, Ozbay AB, Singal AG. Gaps in hepatocellular carcinoma surveillance among insured patients with hepatitis B infection without cirrhosis in the United States. Hepatol Commun 2022; 6:3443-3456. [PMID: 36178256 PMCID: PMC9701467 DOI: 10.1002/hep4.2087] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 07/28/2022] [Accepted: 08/10/2022] [Indexed: 01/21/2023] Open
Abstract
Suboptimal adherence to guidelines for hepatocellular carcinoma (HCC) surveillance among high-risk patients is a persistent problem with substantial detriment to patient outcomes. While patients cite cost as a barrier to surveillance receipt, the financial burden they experience due to surveillance has not been examined. We conducted a retrospective administrative claims study to assess HCC surveillance use and associated costs in a US cohort of insured patients without cirrhosis but with hepatitis B virus (HBV) infection, monitored in routine clinical practice. Of 6831 patients (1122 on antiviral treatment, 5709 untreated), only 39.3% and 51.3% had received any abdominal imaging after 6 and 12 months, respectively, and patients were up to date with HCC surveillance guidelines for only 28% of the follow-up time. Completion of surveillance was substantially higher at 6 and 12 months among treated patients (51.7% and 69.6%, respectively) compared with untreated patients (36.9% and 47.6%, respectively) (p < 0.001). In adjusted models, treated patients were more likely than untreated patients to receive surveillance (hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.53-2.01, p < 0.001), and the proportion of those up to date with surveillance was 9.7% higher (95% CI 6.26-13.07, p < 0.001). Mean total and patient-paid daily surveillance-related costs ranged from $99 (ultrasound) to $334 (magnetic resonance imaging), and mean annual patient costs due to lost productivity for surveillance-related outpatient visits ranged from $93 (using the federal minimum wage) to $321 (using the Bureau of Labor Statistics wage). Conclusion: Use of current HCC surveillance strategies was low across patients with HBV infection, and surveillance was associated with substantial patient financial burden. These data highlight an urgent need for accessible and easy-to-implement surveillance strategies with sufficient sensitivity and specificity for early HCC detection.
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Affiliation(s)
- Mindie H. Nguyen
- Department of Medicine (Gastroenterology and Hepatology) and Department of Epidemiology and Population HealthStanford University Medical CenterPalo AltoCaliforniaUSA
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Ferreira da Silva AC, Cunha-Silva M, Sevá-Pereira T, Mazo DF. Evaluation of the Hepatocellular Carcinoma Predictive Scores PAGE-B and mPAGE-B among Brazilian Patients with Chronic Hepatitis B Virus Infection. Viruses 2022; 14:v14091968. [PMID: 36146774 PMCID: PMC9503912 DOI: 10.3390/v14091968] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 08/28/2022] [Accepted: 09/02/2022] [Indexed: 11/29/2022] Open
Abstract
Hepatitis B virus (HBV) is intrinsically oncogenic and related to hepatocellular carcinoma (HCC). Predictive scores of HCC have been developed but have been poorly studied in admixed populations. Therefore, we aimed to evaluate the performance of PAGE-B and mPAGE-B scores for HCC prediction in HBV Brazilian patients and factors related to HCC occurrence. This is a retrospective study that evaluated patients followed at a tertiary university center. A total of 224 patients were included, with a median follow-up period of 9 years. The mean age at HBV diagnosis was 38.71 ± 14.19 years, predominantly males (66.1%). The cumulative incidence of HCC at 3, 5, and 7 years was 0.993%, 2.70%, and 5.25%, respectively, being related in the univariate logistic regression analysis to male sex (p = 0.0461), older age (p = 0.0001), cirrhosis at HBV diagnosis (p < 0.0001), and higher values of PAGE-B and mPAGE-B scores (p = 0.0002 and p < 0.0001, respectively). Older age, male sex, and cirrhosis at HBV diagnosis were independently associated with HCC occurrence. The AUROCs of PAGE-B and mPAGE-B were 0.7906 and 0.7904, respectively, with no differences between them (p = 0.9767). In conclusion, both PAGE-B and mPAGE-B showed a correct prediction of HCC above 70% in this cohort.
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Affiliation(s)
- Ana Caroline Ferreira da Silva
- Division of Gastroenterology (Gastrocentro), Department of Internal Medicine, School of Medical Sciences of University of Campinas (UNICAMP), Campinas 13083-878, SP, Brazil
| | - Marlone Cunha-Silva
- Division of Gastroenterology (Gastrocentro), Department of Internal Medicine, School of Medical Sciences of University of Campinas (UNICAMP), Campinas 13083-878, SP, Brazil
| | - Tiago Sevá-Pereira
- Division of Gastroenterology (Gastrocentro), Department of Internal Medicine, School of Medical Sciences of University of Campinas (UNICAMP), Campinas 13083-878, SP, Brazil
| | - Daniel F. Mazo
- Division of Gastroenterology (Gastrocentro), Department of Internal Medicine, School of Medical Sciences of University of Campinas (UNICAMP), Campinas 13083-878, SP, Brazil
- Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, University of São Paulo School of Medicine (FMUSP), Sao Paulo 05403-900, SP, Brazil
- Correspondence:
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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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Goldberg D, Mantero A, Kaplan D, Delgado C, John B, Nuchovich N, Emanuel E, Reese PP. Accurate long-term prediction of death for patients with cirrhosis. Hepatology 2022; 76:700-711. [PMID: 35278226 PMCID: PMC9378359 DOI: 10.1002/hep.32457] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Revised: 03/03/2022] [Accepted: 03/08/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Cirrhosis is a major cause of death and is associated with extensive health care use. Patients with cirrhosis have complex treatment choices due to risks of morbidity and mortality. To optimally counsel and treat patients with cirrhosis requires tools to predict their longer-term liver-related survival. We sought to develop and validate a risk score to predict longer-term survival of patients with cirrhosis. APPROACH AND RESULTS We conducted a retrospective cohort study of adults with cirrhosis with no major life-limiting comorbidities. Adults with cirrhosis within the Veterans Health Administration were used for model training and internal validation, and external validation used the OneFlorida Clinical Research Consortium. We used four model-building approaches including variables predictive of cirrhosis-related mortality, focused on discrimination at key time points (1, 3, 5, and 10 years). Among 30,263 patients with cirrhosis ≤75 years old without major life-limiting comorbidities and complete laboratory data during the baseline period, the boosted survival tree models had the highest discrimination, with 1-year, 3-year, 5-year, and 10-year survival rates of 0.77, 0.81, 0.84, and 0.88, respectively. The 1-year, 3-year, and 5-year discrimination was nearly identical in external validation. Secondary analyses with imputation of missing data and subgroups by etiology of liver disease had similar results to the primary model. CONCLUSIONS We developed and validated (internally and externally) a risk score to predict longer-term survival of patients with cirrhosis. This score would transform management of patients with cirrhosis in terms of referral to specialty care and treatment decision-making for non-liver-related care.
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Affiliation(s)
- David Goldberg
- Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL
- Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL
| | - Alejandro Mantero
- Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL
| | - David Kaplan
- Division of Gastroenterology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
- Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
| | - Cindy Delgado
- Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL
| | - Binu John
- Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL
- Bruce Carter VA Medica Center, Miami, FL
| | - Nadine Nuchovich
- Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL
| | - Ezekiel Emanuel
- Department of Medical Ethics and Health Policy, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Peter P. Reese
- Renal-Electrolye and Hypertension Division, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
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Uche-Anya E, Anyane-Yeboa A, Berzin TM, Ghassemi M, May FP. Artificial intelligence in gastroenterology and hepatology: how to advance clinical practice while ensuring health equity. Gut 2022; 71:1909-1915. [PMID: 35688612 DOI: 10.1136/gutjnl-2021-326271] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Accepted: 04/19/2022] [Indexed: 12/12/2022]
Abstract
Artificial intelligence (AI) and machine learning (ML) systems are increasingly used in medicine to improve clinical decision-making and healthcare delivery. In gastroenterology and hepatology, studies have explored a myriad of opportunities for AI/ML applications which are already making the transition to bedside. Despite these advances, there is a risk that biases and health inequities can be introduced or exacerbated by these technologies. If unrecognised, these technologies could generate or worsen systematic racial, ethnic and sex disparities when deployed on a large scale. There are several mechanisms through which AI/ML could contribute to health inequities in gastroenterology and hepatology, including diagnosis of oesophageal cancer, management of inflammatory bowel disease (IBD), liver transplantation, colorectal cancer screening and many others. This review adapts a framework for ethical AI/ML development and application to gastroenterology and hepatology such that clinical practice is advanced while minimising bias and optimising health equity.
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Affiliation(s)
- Eugenia Uche-Anya
- Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Adjoa Anyane-Yeboa
- Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Tyler M Berzin
- Center for Advanced Endoscopy, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Marzyeh Ghassemi
- Institute for Medical and Evaluative Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
| | - Folasade P May
- Vatche and Tamar Manoukian Division of Digestive Diseases, UCLA Kaiser Permanente Center for Health Equity and Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, California, USA
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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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Ramani A, Tapper EB, Griffin C, Shankar N, Parikh ND, Asrani SK. Hepatocellular Carcinoma-Related Mortality in the USA, 1999-2018. Dig Dis Sci 2022; 67:4100-4111. [PMID: 35288828 DOI: 10.1007/s10620-022-07433-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 12/13/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS The burden of hepatocellular carcinoma (HCC) is increasing, and certain groups may be at higher risk. METHODS We analyzed trends in HCC-related mortality in the USA (1999-2018) using national death data. Age-adjusted trends in death rates (annual percentage change, APC) were calculated using joinpoint regression analysis. RESULTS HCC-related death rates increased by 2.1% (95% CI 1.9 to 2.3) annually. Hepatitis C (HCV)-related HCC death rates increased from 1999 to 2012 (8.9%, 95% CI 7.6 to 10.2) followed by a -1.3% (95% CI -3.5 to 0.9) decrease annually. For adults > 65 years, HCV-related HCC death rates increased (7.3% annually, 95% CI 6.5 to 8.1), especially for rural areas (11.1% annually, 95% CI 6.9 to 15.5) with high rates among African-Americans and Hispanics. Increases in non-HCV-related HCC death rates were larger: 13.5% annually (95% CI 3.6 to 24.3, 2005-2010) followed by 4.2% annually (95% CI 2.3 to 6.2, 2010-2018). Annual rates of increase were similar for men (6.8%, 95% CI 5.9 to 7.8) and women (7.0%, 95% CI 5.5 to 8.4) from 1999 to 2018. Rate of increase across races was Whites 8.3% (95% CI 7.2 to 9.4, 1999-2018), African-Americans 11.2% (95% CI -6.6 to 32.3, 2015-2018), and Hispanics 3.7% (95% CI 1.0 to 6.5, 2012-2018). CONCLUSION HCC-related mortality has increased, driven by increases in non-HCV-related mortality with important demographic and regional trends. In addition, HCV-HCC mortality remains high particularly in older persons and those in rural areas despite advances in HCV therapy. These data underscore the need for targeted approaches to mitigate the burden of HCC-related mortality similar to efforts for other cancers.
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Affiliation(s)
- Azaan Ramani
- Baylor University Medical Center, Baylor Scott and White, 3410 Worth Street, Suite 860, Dallas, TX, 75246, USA
| | - Elliot B Tapper
- Division of Gastroenterology and Hepatology, University of Michigan, Michigan, MI, USA.,Gastroenterology Section, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA
| | - Connor Griffin
- Baylor University Medical Center, Baylor Scott and White, 3410 Worth Street, Suite 860, Dallas, TX, 75246, USA
| | - Nagasri Shankar
- Baylor University Medical Center, Baylor Scott and White, 3410 Worth Street, Suite 860, Dallas, TX, 75246, USA
| | - Neehar D Parikh
- Division of Gastroenterology and Hepatology, University of Michigan, Michigan, MI, USA
| | - Sumeet K Asrani
- Baylor University Medical Center, Baylor Scott and White, 3410 Worth Street, Suite 860, Dallas, TX, 75246, USA.
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Ayoub WS, Jones PD, Yang JD, Martin P. Emerging drugs for the treatment of hepatocellular carcinoma. Expert Opin Emerg Drugs 2022; 27:141-149. [PMID: 35642526 DOI: 10.1080/14728214.2022.2083107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
INTRODUCTION Hepatocellular carcinoma (HCC) remains a leading cause of liver related mortality. Cirrhosis of any etiology is the major risk factor although HCC can develop in its absence in patients with Hepatitis B and increasingly in those with non-alcoholic fatty liver disease. When detected at an early stage, curative options include surgical resection, liver transplantation and/or ablative therapies. Unfortunately, most cases of HCC are recognized at an advanced state when options are limited and non-curative. However new systemic therapies with tyrosine kinase inhibitors and immunotherapy have expanded therapeutic options in advanced HCC. Advances in systemic therapy have given patients with advanced HCC hope and prolonged their survival. Ongoing trials addressing different combination therapies with checkpoint inhibitors, tyrosine kinase inhibitors (TKI) or anti-VEGF therapies are expected to further enhance the management of advanced HCC. AREAS COVERED We discuss recent data and ongoing research efforsts to improve the treatment of hepatocellular carcinoma with discussion of current and upcoming systemic therapy combining agents of different classes. EXPERT OPINION Sustemic therapy for HCC is in evolution. The inclusion of immunotherapy to systemic therapy has revolutionalized the field of HCC treatment. Identificantion of the appropriate combination and sequence of systemic therapy coupled with discovery of reliable HCC biomarkers will lead to improved survival and inidividulized HCC therapy.
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Affiliation(s)
- Walid S Ayoub
- Cedars-Sinai Medical Center, Los Angeles, United States
| | - Patricia D Jones
- University of Miami Miller School of Medicine, Miami, Florida, United States
| | - Ju Dong Yang
- Cedars-Sinai Medical Center, Los Angeles, United States
| | - Paul Martin
- University of Miami Miller School of Medicine, Miami, Florida, United States
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Polanco PM, Ju MR, Chansard M, Mathew Augustine M, Meier J, Mortensen E, Zeh HJ, Yopp AC. Trends and Disparities in Treatment Utilization for Early-Stage Hepatocellular Carcinoma in the Veteran Population. Ann Surg Oncol 2022; 29:5488-5497. [DOI: 10.1245/s10434-022-11897-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Accepted: 04/28/2022] [Indexed: 12/24/2022]
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Reinoso-Pereira GL, Paranaguá-Vezozzo DC, Mazo DF, França JID, Ono SK, Carrilho FJ. HIGH VALUES OF LIVER STIFFNESS PLAY AN IMPORTANT ROLE IN STRATIFYING THE RISK OF HEPATOCELLULAR CARCINOMA IN CIRRHOTIC HEPATITIS C PATIENTS. ARQUIVOS DE GASTROENTEROLOGIA 2022; 59:204-211. [PMID: 35830030 DOI: 10.1590/s0004-2803.202202000-38] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Accepted: 02/23/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND Evaluate the role of liver stiffness measurement (LSM) by transient elastography (TE) as a risk factor for hepatocellular carcinoma (HCC) occurrence in a prospective cohort of Brazilian hepatitis C virus (HCV) patients with cirrhosis. METHODS A cohort of 99 consecutive HCV patients was included between 2011 and 2016 with baseline LSM ≥12 kilopascals (kPa). Baseline variables were evaluated and HCC occurrence was documented. Kaplan-Meier methods with a log-rank test and the use of cox univariate and multivariate analysis assessed the association between variables and clinical results. RESULTS The mean age was 57.8±10.6 years. In a follow-up over a mean of 3.3 years, 20 (20.2%) patients developed HCC. In univariate logistic regression analysis, variables associated with HCC occurrence were: lower platelet count (P=0.0446), higher serum alpha-fetoprotein (P=0.0041) and bilirubin (P=0.0008) values, higher Model for End-Stage Liver Disease (MELD) score (P=0.0068) and higher LSM (P=0.0354). LSM evaluated by TE was independently associated with HCC development, and the best cut-off value for higher HCC risk was >21.1 kPa (HR: 5.548; 95%CI: 1.244-24.766; P=0.025). CONCLUSION A high value of liver stiffness relates substantially to an increased risk for HCC occurrence in Brazilian patients with cirrhosis due to HCV.
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Affiliation(s)
- Gleicy Luz Reinoso-Pereira
- Faculdade de Medicina da Universidade de São Paulo, Departamento de Gastroenterologia, Divisão de Gastroenterologia Clínica e Hepatologia, São Paulo, SP, Brasil
| | - Denise Cerqueira Paranaguá-Vezozzo
- Faculdade de Medicina da Universidade de São Paulo, Departamento de Gastroenterologia, Divisão de Gastroenterologia Clínica e Hepatologia, São Paulo, SP, Brasil
- Grupo São Paulo Clínicas de Câncer de Fígado, São Paulo, SP, Brasil
| | - Daniel F Mazo
- Faculdade de Medicina da Universidade de São Paulo, Departamento de Gastroenterologia, Divisão de Gastroenterologia Clínica e Hepatologia, São Paulo, SP, Brasil
- Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Divisão de Gastroenterologia-Gastrocentro, Campinas, SP, Brasil
| | - João Italo Dias França
- Faculdade de Medicina da Universidade de São Paulo, Departamento de Gastroenterologia, Divisão de Gastroenterologia Clínica e Hepatologia, São Paulo, SP, Brasil
| | - Suzane Kioko Ono
- Faculdade de Medicina da Universidade de São Paulo, Departamento de Gastroenterologia, Divisão de Gastroenterologia Clínica e Hepatologia, São Paulo, SP, Brasil
- Grupo São Paulo Clínicas de Câncer de Fígado, São Paulo, SP, Brasil
| | - Flair José Carrilho
- Faculdade de Medicina da Universidade de São Paulo, Departamento de Gastroenterologia, Divisão de Gastroenterologia Clínica e Hepatologia, São Paulo, SP, Brasil
- Grupo São Paulo Clínicas de Câncer de Fígado, São Paulo, SP, Brasil
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Identification of CCL20 and LCN2 as Efficient Serological Tools for Detection of Hepatocellular Carcinoma. DISEASE MARKERS 2022; 2022:7758735. [PMID: 35308139 PMCID: PMC8930252 DOI: 10.1155/2022/7758735] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/25/2021] [Accepted: 02/26/2022] [Indexed: 11/18/2022]
Abstract
Objectives To discover a more powerful diagnostic tool for the detection of hepatocellular carcinoma (HCC). Methods 16 extracellularly located candidates were selected by analyzing the expression array datasets in GEO. 10 of them were validated in clinical samples by ELISA. Differences of each variable were compared by one-way ANOVA or Kruskal-Wallis test. CCL20 and LCN2 were determined in all samples (HCC, 167; liver cirrhosis, 106; and healthy control, 106) and finally chosen for the construction of the combination model by binary logistic regression. The models were first built using a comprehensive control, including both liver cirrhosis (LC) and healthy donors. Then, the models were rebuilt by using the LC group alone as a control. ROC analysis was performed to compare the diagnostic efficiency of each indicator. Results Levels of CCL20 and LCN2 in HCC sera were significantly higher than those in all controls. Using the comprehensive control, ROC curves showed that the optimum diagnostic cutoff of the CCL20 and LCN2 combination was 0.443 (area under curve (AUC) of 0.927 (95% CI 0.896-0.951), sensitivity of 0.808, specificity of 0.892, and accuracy of 0.859). For detection of HCC from LC control, the optimum diagnostic cutoff was 0.590 (AUC of 0.919 (95% CI 0.880-0.948), sensitivity of 0.814, specificity of 0.868, and accuracy of 0.834). Furthermore, the model maintained diagnostic accuracy for patients with HCC in the early stage, with the sensitivity and specificity of 0.75 and 0.77 from LC control, yet the AFP only reached 0.5 and 0.67, respectively. Conclusion A combination model composed of CCL20 and LCN2 may serve as a more efficient tool for distinguishing HCC from nonmalignant liver diseases.
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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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Provider Attitudes Toward Risk-Based Hepatocellular Carcinoma Surveillance in Patients With Cirrhosis in the United States. Clin Gastroenterol Hepatol 2022; 20:183-193. [PMID: 32927050 PMCID: PMC8657369 DOI: 10.1016/j.cgh.2020.09.015] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 09/01/2020] [Accepted: 09/04/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Hepatocellular carcinoma (HCC) surveillance rates are suboptimal in clinical practice. We aimed to elicit providers' opinions on the following aspects of HCC surveillance: preferred strategies, barriers and facilitators, and the impact of a patient's HCC risk on the choice of surveillance modality. METHODS We conducted a web-based survey among gastroenterology and hepatology providers (40% faculty physicians, 21% advanced practice providers, 39% fellow-trainees) from 26 US medical centers in 17 states. RESULTS Of 654 eligible providers, 305 (47%) completed the survey. Nearly all (98.4%) of the providers endorsed semi-annual HCC surveillance in patients with cirrhosis, with 84.2% recommending ultrasound ± alpha fetoprotein (AFP) and 15.4% recommending computed tomography (CT) or magnetic resonance imaging (MRI). Barriers to surveillance included limited HCC treatment options, screening test effectiveness to reduce mortality, access to transportation, and high out-of-pocket costs. Facilitators of surveillance included professional society guidelines. Most providers (72.1%) would perform surveillance even if HCC risk was low (≤0.5% per year), while 98.7% would perform surveillance if HCC risk was ≥1% per year. As a patient's HCC risk increased from 1% to 3% to 5% per year, providers reported they would be less likely to order ultrasound ± AFP (83.6% to 68.9% to 57.4%; P < .001) and more likely to order CT or MRI ± AFP (3.9% to 26.2% to 36.1%; P < .001). CONCLUSIONS Providers recommend HCC surveillance even when HCC risk is much lower than the threshold suggested by professional societies. Many appear receptive to risk-based HCC surveillance strategies that depend on patients' estimated HCC risk, instead of our current "one-size-fits all" strategy.
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Benhammou JN, Lin J, Aby ES, Markovic D, Raman SS, Lu DS, Tong MJ. Nonalcoholic fatty liver disease-related hepatocellular carcinoma growth rates and their clinical outcomes. HEPATOMA RESEARCH 2021; 7. [PMID: 34966854 PMCID: PMC8713558 DOI: 10.20517/2394-5079.2021.74] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Aim: Nonalcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC) is projected to become the leading indication for liver transplantation. Previous studies indicate that tumor growth rates (TGR) may predict survival and were helpful in determining HCC surveillance intervals. Therefore, we aimed to determine its usefulness in predicting clinical outcomes and treatments. Methods: We conducted a retrospective study of hepatitis B, C and NAFLD-HCC cases. TGR was measured using 2-consecutive pre-treatment contrast-enhanced imaging studies ≥ 25 days apart. A multivariate regression model was used to determine predictors of TGR. In addition, the Cox regression model was used to evaluate the relationship between TGR and overall survival. Results: From 2000–2019, the study cohort comprised 38, 60, and 47 HBV, HCV, and NAFLD patients, respectively, with TGRs. NAFLD-HCC tumor size was inversely correlated to the extent of liver disease as measured by Child-Pugh score (7.2 cm in non-cirrhosis; 3.7 cm, 2.6 cm, and 2.1 cm in Child A, B, and C, respectively; P < 0.001). After adjusting for baseline characteristics, the TGR per month was fastest in HBV (9.4%, 95%CI: 6.3%-12.5%) compared to HCV (4.9%, 95%CI: 2.8%-7%) and NAFLD patients (3.6%, 95%CI: 1.6%-6.7%). Predictors of TGR included elevated AFP, low albumin, and smaller tumor size. Fast TGR in viral etiologies had higher mortality [adj. hazard ratio (HR) = 2.6, 95%CI: 1.2–5.7, P = 0.02] than slow TGRs, independent of treatments. Fast TGR in NAFLD had a trend towards higher mortality (HR = 3.6, 95%CI: 0.95–13.3, P = 0.059). Conclusion: NAFLD-HCC patients have more indolent growths than viral-related HCC TGRs. The addition of TGR as a biomarker may assist in stratifying treatment options.
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Affiliation(s)
- Jihane N Benhammou
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine, Los Angeles, CA 90095, USA.,Division of Gastroenterology, Hepatology and Parenteral Nutrition, Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90075, USA.,Pfleger Liver Institute, University of California, Los Angeles, CA 90095, USA
| | - Jonathan Lin
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine, Los Angeles, CA 90095, USA
| | - Elizabeth S Aby
- Gastroenterology, Hepatology, Liver Transplantation and Nutrition, University of Minnesota, Minneapolis, MN 55455, USA
| | - Daniela Markovic
- Department of Biomathematics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
| | - Steven S Raman
- Department of Radiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
| | - David S Lu
- Department of Radiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
| | - Myron J Tong
- Pfleger Liver Institute, University of California, Los Angeles, CA 90095, USA.,Liver Center, Huntington Medical Research Institutes, Pasadena, CA 91105, USA
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Low ESL, Apostolov R, Wong D, Lin S, Kutaiba N, Grace JA, Sinclair M. Hepatocellular carcinoma surveillance and quantile regression for determinants of underutilisation in at-risk Australian patients. World J Gastrointest Oncol 2021; 13:2149-2160. [PMID: 35070048 PMCID: PMC8713329 DOI: 10.4251/wjgo.v13.i12.2149] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Revised: 07/13/2021] [Accepted: 09/19/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND While clinical guidelines recommend hepatocellular carcinoma (HCC) surveillance for at-risk individuals, reported surveillance rates in the United States and Europe remain disappointingly low.
AIM To quantify HCC surveillance in an Australian cohort, and assess for factors associated with surveillance underutilisation.
METHODS All patients undergoing HCC surveillance liver ultrasounds between January 1, 2018 to June 30, 2018 at a tertiary hospital in Melbourne, Australia, were followed until July 31, 2020, or when surveillance was no longer required. The primary outcome was the percentage of time up-to-date with HCC surveillance (PTUDS). Quantile regression was performed to determine the impact of factors associated with HCC surveillance underutilisation.
RESULTS Among 775 at-risk patients followed up for a median of 27.5 months, the median PTUDS was 84.2% (IQR: 66.3%-96.3%). 85.0% of patients were followed up by specialist gastroenterologists. Amongst those receiving specialist care, quantile regression demonstrated differential associations at various quantile levels of PTUDS for several factors. Older age at the 25th quantile (estimate 0.002 per percent, P = 0.03), and cirrhotic status at the 75th quantile (estimate 0.021, P = 0.017), were significantly associated with greater percentage of time up-to-date. African ethnicity (estimate -0.089, P = 0.048) and a culturally and linguistically diverse (CALD) background (estimate -0.063, P = 0.01) were significantly associated with lower PTUDS at the 50th quantile, and again for CALD at the 75th quantile (estimate -0.026, P = 0.045).
CONCLUSION While median PTUDS in this Australian cohort study was 84.2%, awareness of the impact of specific factors across PTUDS quantiles can aid targeted interventions towards improved HCC surveillance.
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Affiliation(s)
- Elizabeth SL Low
- Department of Gastroenterology and Liver Transplant Unit, Austin Health, Heidelberg 3084, Victoria, Australia
| | - Ross Apostolov
- Department of Gastroenterology and Liver Transplant Unit, Austin Health, Heidelberg 3084, Victoria, Australia
- Department of Medicine, University of Melbourne, Melbourne 3000, Victoria, Australia
| | - Darren Wong
- Department of Gastroenterology and Liver Transplant Unit, Austin Health, Heidelberg 3084, Victoria, Australia
| | - Sandra Lin
- Department of Radiology, Monash Health, Clayton 3168, Victoria, Australia
| | - Numan Kutaiba
- Department of Radiology, Austin Health, Heidelberg 3084, Victoria, Australia
| | - Josephine A Grace
- Department of Gastroenterology and Liver Transplant Unit, Austin Health, Heidelberg 3084, Victoria, Australia
- Department of Medicine, University of Melbourne, Melbourne 3000, Victoria, Australia
| | - Marie Sinclair
- Department of Gastroenterology and Liver Transplant Unit, Austin Health, Heidelberg 3084, Victoria, Australia
- Department of Medicine, University of Melbourne, Melbourne 3000, Victoria, Australia
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Focused Education Increases Hepatocellular Cancer Screening in Patients with Cirrhosis Regardless of Functional Health Literacy. Dig Dis Sci 2021; 66:2603-2609. [PMID: 32889600 PMCID: PMC7933309 DOI: 10.1007/s10620-020-06583-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Accepted: 08/23/2020] [Indexed: 12/30/2022]
Abstract
BACKGROUND Health education interventions are successful in modifying lifestyle. Functional health literacy (FHL) can determine patient adherence to clinic visits and procedures and may adversely impact the success of these interventions. AIMS We sought to evaluate the hypothesis that a health education intervention would improve compliance with hepatocellular cancer (HCC) screening and that poor FHL would reduce such compliance. METHODS We assessed FHL using a short version test of functional health literacy in adults (STOFHLA). Cirrhotic patients free of HCC were prospectively enrolled from clinics and provided an educational intervention consisting of focused physician-led discussion regarding cirrhosis and HCC, along with written material on these topics for the subject to review at home. Patients were subsequently followed for 6 months (prospective time period), and the same cohort's clinic/HCC screening behavior between 6 and 12 months prior to the educational intervention (retrospective time period) was compared. RESULTS In total, 104 cirrhotic patients (age 60.01 ± 8.58 years, 80% men, MELD 12.70 ± 5.76) were included. Of these, 89 (85.57%) of patients had educational level 12th grade and higher. There were 76% (n = 79) with adequate, while 24% (n = 25) had inadequate/marginal FHL on S-TOHFLA. The number of HCC-related imaging increased from 59 (56.7%) to 86 (82.6%, p < 0.0001) post-education in the prospective compared to prior time period which was similar regardless of FHL. CONCLUSIONS While the educational intervention was successful in improving compliance with HCC screenings, FHL status did not impact the power of this intervention. Hence, the combination of specific verbal information, along with targeted written material, improved compliance with clinic visits and liver imaging for HCC.
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Sachar Y, Brahmania M, Dhanasekaran R, Congly SE. Screening for Hepatocellular Carcinoma in Patients with Hepatitis B. Viruses 2021; 13:1318. [PMID: 34372524 PMCID: PMC8310362 DOI: 10.3390/v13071318] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 07/05/2021] [Accepted: 07/05/2021] [Indexed: 12/18/2022] Open
Abstract
Chronic hepatitis B (CHB) infection is a significant risk factor for developing hepatocellular carcinoma (HCC). As HCC is associated with significant morbidity and mortality, screening patients with CHB at a high risk for HCC is recommended in an attempt to improve these outcomes. However, the screening recommendations on who to screen and how often are not uniform. Identifying patients at the highest risk of HCC would allow for the best use of health resources. In this review, we evaluate the literature on screening patients with CHB for HCC, strategies for optimizing adherence to screening, and potential risk stratification tools to identify patients with CHB at a high risk of developing HCC.
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Affiliation(s)
- Yashasavi Sachar
- London Health Sciences Center, Department of Medicine, Division of Gastroenterology, Western University, London, ON N6A 5A5, Canada; (Y.S.); (M.B.)
| | - Mayur Brahmania
- London Health Sciences Center, Department of Medicine, Division of Gastroenterology, Western University, London, ON N6A 5A5, Canada; (Y.S.); (M.B.)
- Centre for Quality, Innovation and Safety, Schulich School of Medicine & Dentistry, Western University, London, ON N6A 5W9, Canada
| | - Renumathy Dhanasekaran
- Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University, Stanford, CA 94305, USA;
| | - Stephen E. Congly
- Department of Medicine, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4Z6, Canada
- O’Brien Institute of Public Health, University of Calgary, Calgary, AB T2N 4Z6, Canada
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Liu C, Zhu X, Jia Y, Chi F, Qin K, Pei J, Zhang C, Mu X, Zhang H, Dong X, Xu J, Yu B. Dasatinib inhibits proliferation of liver cancer cells, but activation of Akt/mTOR compromises dasatinib as a cancer drug. Acta Biochim Biophys Sin (Shanghai) 2021; 53:823-836. [PMID: 33961012 DOI: 10.1093/abbs/gmab061] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Indexed: 12/15/2022] Open
Abstract
Dasatinib is a multi-target protein tyrosine kinase inhibitor. Due to its potent inhibition of Src, Abl, the platelet-derived growth factor receptor (PDGFR) family kinases, and other oncogenic kinases, it has been investigated as a targeted therapy for a broad spectrum of cancer types. However, its efficacy has not been significantly extended beyond leukemia. The mechanism of resistance to dasatinib in a wide array of cancers is not clear. In the present study, we investigated the effect of dasatinib on hepatocellular carcinoma cell growth and explored the underlying mechanisms. Our results showed that dasatinib potently inhibited the proliferation of SNU-449 cells, but not that of other cell lines, such as SK-Hep-1, even though it inhibited the phosphorylation of Src on both negative and positive regulation sites in all these cells. Dasatinib activated the phosphoinositide-dependent protein kinase1 (PDK1)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway in SK-Hep-1 cells, but not in SNU-449 cells. Blocking the Akt/mTOR signaling pathway strongly promoted the efficacy of dasatinib in SK-Hep-1 cells. In SNU-449 cells, dasatinib promoted apoptosis and the cleavage of caspase-3 and caspase-7, induced cell cycle arrest in the G1 phase, and inhibited the expression of Cyclin-dependent kinase (CDK4)/6/CyclinD1 complex. These findings demonstrate that dasatinib exerts its anti-proliferative effect on hepatocellular cell proliferation by blocking the Src family kinases; however, it causes Akt activation, which compromises dasatinib as an anti-cancer drug.
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Affiliation(s)
- Chang Liu
- Department of Biochemistry and Molecular Biology, Changzhi Medical College, Changzhi 046000, China
- Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China
| | - Xiaoxia Zhu
- Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China
| | - Yuqi Jia
- Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China
| | - Fenqing Chi
- Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China
| | - Keru Qin
- Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China
| | - Jinhong Pei
- Department of Biochemistry and Molecular Biology, Changzhi Medical College, Changzhi 046000, China
| | - Chan Zhang
- Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China
| | - Xiuli Mu
- Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China
| | - Hongwei Zhang
- Department of Hematology, Affiliated Tumor Hospital of Shanxi Medical University, Taiyuan 030013, China
| | - Xiushan Dong
- Department of General Surgery, Shanxi Bethune Hospital, Taiyuan 030032, China
| | - Jun Xu
- Department of General Surgery, The First Hospital of Shanxi Medical University, Taiyuan 030001, China
| | - Baofeng Yu
- Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China
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A Latin American survey on demographic aspects of hospitalized, decompensated cirrhotic patients and the resources for their management. Ann Hepatol 2021; 19:396-403. [PMID: 32418749 DOI: 10.1016/j.aohep.2020.03.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 03/19/2020] [Accepted: 03/25/2020] [Indexed: 02/04/2023]
Abstract
INTRODUCTION & OBJECTIVES Liver cirrhosis is a major cause of mortality worldwide. Adequate diagnosis and treatment of decompensating events requires of both medical skills and updated technical resources. The objectives of this study were to search the demographic profile of hospitalized cirrhotic patients in a group of Latin American hospitals and the availability of expertise/facilities for the diagnosis and therapy of decompensation episodes. METHODS A cross sectional, multicenter survey of hospitalized cirrhotic patients. RESULTS 377 patients, (62% males; 58±11 years) (BMI>25, 57%; diabetes 32%) were hospitalized at 65 centers (63 urbans; 57 academically affiliated) in 13 countries on the survey date. Main admission causes were ascites, gastrointestinal bleeding, hepatic encephalopathy and spontaneous bacterial peritonitis/other infections. Most prevalent etiologies were alcohol-related (AR) (40%); non-alcoholic-steatohepatitis (NASH) (23%), hepatitis C virus infection (HCV) (7%) and autoimmune hepatitis (AIH) (6%). The most frequent concurrent etiologies were AR+NASH. Expertise and resources in every analyzed issue were highly available among participating centers, mostly accomplishing valid guidelines. However, availability of these facilities was significantly higher at institutions located in areas with population>500,000 (n=45) and in those having a higher complexity level (Gastrointestinal, Liver and Internal Medicine Departments at the same hospital (n=22). CONCLUSIONS The epidemiological etiologic profile in hospitalized, decompensated cirrhotic patients in Latin America is similar to main contemporary emergent agents worldwide. Medical and technical resources are highly available, mostly at great population urban areas and high complexity medical centers. Main diagnostic and therapeutic approaches accomplish current guidelines recommendations.
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Mahmud N, Kaplan DE, Goldberg DS, Taddei TH, Serper M. Changes in Hepatocellular Carcinoma Surveillance and Risk Factors for Noncompletion in the Veterans Health Administration Cohort During the Coronavirus Disease 2019 Pandemic. Gastroenterology 2021; 160:2162-2164.e3. [PMID: 33434604 PMCID: PMC8142896 DOI: 10.1053/j.gastro.2021.01.007] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Revised: 12/28/2020] [Accepted: 01/07/2021] [Indexed: 02/06/2023]
Affiliation(s)
- Nadim Mahmud
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; Gastroenterology Section, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania; Leonard Davis Institute of Health Economics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania.
| | - David E. Kaplan
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania,Gastroenterology Section, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania
| | - David S. Goldberg
- Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, Miami, Florida
| | - Tamar H. Taddei
- Division of Digestive Diseases, Yale University School of Medicine, New Haven, Connecticut,VA Connecticut Healthcare System, West Haven, Connecticut
| | - Marina Serper
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania,Gastroenterology Section, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania,Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania
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Debes JD, Romagnoli PA, Prieto J, Arrese M, Mattos AZ, Boonstra A. Serum Biomarkers for the Prediction of Hepatocellular Carcinoma. Cancers (Basel) 2021; 13:cancers13071681. [PMID: 33918270 PMCID: PMC8038187 DOI: 10.3390/cancers13071681] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 03/22/2021] [Accepted: 03/28/2021] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of global cancer death. Major etiologies of HCC relate to chronic viral infections as well as metabolic conditions. The survival rate of people with HCC is very low and has been attributed to late diagnosis with limited treatment options. Combining ultrasound and the biomarker alpha-fetoprotein (AFP) is currently one of the most widely used screening combinations for HCC. However, the clinical utility of AFP is controversial, and the frequency and operator-dependence of ultrasound lead to a variable degree of sensitivity and specificity across the globe. In this review, we summarize recent developments in the search for non-invasive serum biomarkers for early detection of HCC to improve prognosis and outcome for patients. We focus on tumor-associated protein markers, immune mediators (cytokines and chemokines), and micro-RNAs in serum or circulating extracellular vesicles and examine their potential for clinical application.
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Affiliation(s)
- José D. Debes
- Department of Gastroenterology and Hepatology, Erasmus MC Rotterdam, 3015 CE Rotterdam, The Netherlands
- Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA
- Correspondence: (J.D.D.); (A.B.)
| | - Pablo A. Romagnoli
- Centro de Investigaciones en Medicina Translacional “Severo Amuchastegui” (CIMETSA), Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC), Córdoba 5016, Argentina;
| | - Jhon Prieto
- Centro de Enfermedades Hepaticas y Digestivas, Bogota CS412, Colombia;
| | - Marco Arrese
- Department of Gastroenterology, Escuela de Medicina, & Centro de Envejecimiento y Regeneración (CARE), Pontificia Universidad Católica de Chile, Santiago 8330077, Chile;
| | - Angelo Z. Mattos
- Graduate Program in Medicine: Hepatology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porte Alegre 90050-170, Brazil;
| | - André Boonstra
- Department of Gastroenterology and Hepatology, Erasmus MC Rotterdam, 3015 CE Rotterdam, The Netherlands
- Correspondence: (J.D.D.); (A.B.)
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Anugwom CM, Allaire M, Akbar SMF, Sultan A, Bollipo S, Mattos AZ, Debes JD. Hepatitis B-related hepatocellular carcinoma: surveillance strategy directed by immune-epidemiology. HEPATOMA RESEARCH 2021; 7. [PMID: 33884303 PMCID: PMC8057710 DOI: 10.20517/2394-5079.2021.06] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Hepatitis B infection (HBV) is one of the most common causes of hepatocellular carcinoma (HCC) worldwide. The age of occurrence, prognosis and incidence vary dramatically depending on the region of the world. This geographic variation is largely dependent on the contrasting incidence of HBV, age of transmission of the virus, the timing of integration into the human genome, and different HBV genotypes, as well as environmental factors. It results in a wide difference in viral interaction with the immune system, genomic modulation and the consequent development of HCC in an individual. In this review, we describe many factors implicated in HCC development, provide insight regarding at-risk populations and explain societal recommendations for HCC surveillance in persons living with HBV in different continents of the world.
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Affiliation(s)
- Chimaobi M Anugwom
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis 55455, USA
| | - Manon Allaire
- Sorbonne Université, Service d'Hépatologie, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, AP-HP, Paris 75103, France.,Inserm U1149, Centre de Recherche sur l'Inflammation, France Faculté de Médecine, Xavier Bichat, Université Paris Diderot, Paris 75108, France
| | - Sheikh Mohammad Fazle Akbar
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon 791-0295, Japan
| | - Amir Sultan
- College of Health Sciences, Addis Ababa University, Tikur Anbessa Specialized Hospital, Addis Ababa 5657, Ethiopia
| | - Steven Bollipo
- Department of Gastroenterology, John Hunter Hospital, Newcastle, Australia & School of Medicine & Public Health, University of Newcastle, New South Wales 2310, Australia
| | - Angelo Z Mattos
- Graduate Program in Medicine: Hepatology, Federal University of Health Sciences of Porto Alegre 90050-170, Brazil.,Gastroenterology and Hepatology Unit, Irmandade Santa Casa de Misericórdia de Porto Alegre 90020-090, Brazil
| | - Jose D Debes
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis 55455, USA.,Department of Medicine, Division of Infectious Diseases, University of Minnesota, Minneapolis, MN 55455, USA.,Department of Gastroenterology & Hepatology, Erasmus MC, Rotterdam 3015-CE, Netherlands
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