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Ben Yedder N, Girot P, Koudougou C, Schnee M, Métairie S, Lim A, Soualah K, Andrault S, Salimon M, Touchefeu Y. Lack of prior screening for advanced liver fibrosis in patients with newly diagnosed hepatocellular carcinoma: Results from a prospective multicentre study. Clin Res Hepatol Gastroenterol 2025; 49:102607. [PMID: 40315983 DOI: 10.1016/j.clinre.2025.102607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2025] [Revised: 03/29/2025] [Accepted: 04/28/2025] [Indexed: 05/04/2025]
Abstract
INTRODUCTION Hepatocellular carcinoma (HCC) most commonly occurs in a cirrhotic liver. In France, a screening rate of 20 % to 35 % has been reported in clinical cohorts. In these studies, patients were generally enrolled in centers of the same category (university or general hospitals). The aim of this study was to prospectively investigate the circumstances of HCC diagnosis and the causes of HCC screening failure in a cohort of patients from a regional network. METHODS This prospective multicenter study enrolled patients with newly diagnosed HCC from October 2022 to July 2024. Investigators were from one university hospital, two private clinics, and three general hospitals. RESULTS Two hundred patients were included. Diagnosis was made by screening in 31.0 % of cases. Most patients had comorbidities that could lead to screening for liver fibrosis: current or past history of alcohol consumption (74.6 %), diabetes (51.4 %), hypertension (75.7 %), dyslipidemia (47.4 %). The FIB-4 score was ≥ 2.67 in 74.5 % of patients in the "in screening" group and 63.9 % in the "not in -screening" group. Among the 138 patient in the "not in screening" group, 115 (83.3 %), 34 (24.6), 23 (16.7 %) and 13 (9.4 %) declared they had visited a general practionner, a cardiologist, a gastroenterologist, and/or an endocrinologist within the 12 months prior to HCC diagnosis, respectively. CONCLUSION Recognition by general practitioners of patients at risk of chronic liver disease and identification of advanced fibrosis are major areas for optimization of HCC screening.
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Affiliation(s)
- Nour Ben Yedder
- Nantes Université, CHU Nantes, Institut des Maladies de l'Appareil Digestif (IMAD), Hépato-Gastroentérologie, Inserm CIC 1413, F-44000 Nantes, France
| | - Paul Girot
- Gastroenterology Department, Centre Hospitalier Départemental Vendée, La Roche-Sur-Yon, France
| | - Carelle Koudougou
- Department of Gastroenterology, Clinique Jules Verne, Nantes, France
| | - Matthieu Schnee
- Gastroenterology Department, Centre Hospitalier Départemental Vendée, La Roche-Sur-Yon, France
| | - Sylvie Métairie
- Department of Oncological, Digestive and Endocrine Surgery, University Hospital of Nantes, Nantes, France
| | - Annie Lim
- Department of Gastroenterology, Clinique Santé Atlantique, Saint Herblain, France
| | - Kouceila Soualah
- Centre Hospitalier Châteaubriant Nozay Pouancé, Châteaubriant, France
| | - Samuel Andrault
- Gastroenterology Department, Centre Hospitalier, Cholet, France
| | - Maëva Salimon
- Department of Gastroenterology, Clinique Santé Atlantique, Saint Herblain, France
| | - Yann Touchefeu
- Nantes Université, CHU Nantes, Institut des Maladies de l'Appareil Digestif (IMAD), Hépato-Gastroentérologie, Inserm CIC 1413, F-44000 Nantes, France.
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El-Azab GI, El-Helw GAA, Elsabaawy MMA, Kohla MAS, Omar YAM. Evaluation of screening program for hepatocellular carcinoma at a single center. EGYPTIAN LIVER JOURNAL 2025; 15:2. [DOI: 10.1186/s43066-025-00404-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Accepted: 01/16/2025] [Indexed: 03/04/2025] Open
Abstract
Abstract
Background
Hepatocellular carcinoma (HCC) is the seventh most common cancer in the world and is a form of liver cancer that starts in the cells of the liver. The best way to increase the chances of survival for people at high risk for HCC is to detect it early through regular monitoring. For monitoring purposes, it is recommended to conduct ultrasound exams every 4 to 6 months, sometimes in combination with alpha-fetoprotein tests.
Aim of the work
Assess the HCC surveillance and its ability to detect HCC patients early on and improve their management.
Patients and methods
The study involved 300 patients of hepatocellular carcinoma (HCC) investigated at Menoufia University’s Institute of National Liver in Egypt. Patients were evaluated using the Liver Cancer of Barcelona Clinic (BCLC) staging system. Furthermore, the patients were classified into three surveillance categories: no surveillance, routine surveillance, and sporadic surveillance.
Results
A substantial difference statistically among the groups that received and did not receive surveillance with consideration for the stage of hepatocellular carcinoma (HCC) in particular was found. Patients who were observed usually got their diagnoses earlier. Those who were not under surveillance frequently had advanced cases of hepatocellular carcinoma upon diagnosis (HCC).
Conclusion
High-risk patients were regularly investigated for having HCC is necessary for early disease detection, appropriate therapy, and improved survival. Consistent monitoring with AFP and ultrasound allows for early detection of HCC.
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Toy M, Hutton D, Conners EE, Pham H, Salomon JA, So S. Cost-effectiveness of monitoring and liver cancer surveillance among patients with inactive chronic hepatitis B. PLoS One 2025; 20:e0313898. [PMID: 39841655 PMCID: PMC11753660 DOI: 10.1371/journal.pone.0313898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Accepted: 01/06/2025] [Indexed: 01/24/2025] Open
Abstract
Patients with chronic hepatitis B infection (CHB) have an increased risk for death from liver cirrhosis and hepatocellular carcinoma (HCC). In the United States, only an estimated 37% of adults with chronic hepatitis B diagnosis without cirrhosis receive monitoring with at least an annual alanine transaminase (ALT) and hepatitis B deoxyribonucleic acid (DNA), and an estimated 59% receive antiviral treatment when they develop active hepatitis or cirrhosis. A Markov model was used to calculate the costs, health impact and cost-effectiveness of increased monitoring of adults with HBeAg negative inactive or HBeAg positive immune tolerant CHB who have no cirrhosis or significant fibrosis and are not recommended by the current American Association for the Study of Liver Diseases (AASLD) clinical practice guidelines to receive antiviral treatment, and to assess whether the addition of HCC surveillance would be cost-effective. For every 100,000 adults with CHB who were initially not recommended for treatment, if the monitoring rate increased from the current 37% to 90% and treatment rate increased from 59% to 80%, 4,600 cases of cirrhosis, 2,450 cases of HCC and 4,700 HBV-related deaths would be averted with a gain of 45,000 QALYs and a savings of $180 million in lifetime health care costs. At a willingness to pay threshold of $100,000/QALY, the addition of HCC surveillance with the standard recommended biannual liver ultrasound and alfa fetoprotein levels is likely cost-effective if the HCC risk ≥ 0.55%/year. Regular monitoring of persons with inactive or immune tolerant CHB who are initially not recommended to receive antiviral treatment in the United States is cost-saving. The addition of HCC surveillance with biannual US and AFP would be cost-effective for individuals with HCC incidence ≥ 0.55%/year.
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Affiliation(s)
- Mehlika Toy
- Erasmus School of Health Policy & Management, Erasmus University, Rotterdam, The Netherlands
| | - David Hutton
- Department of Health Management and Policy, University of Michigan, Ann Arbor, Michigan, United States of America
| | - Erin E. Conners
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - Hang Pham
- Department of Surgery, Asian Liver Center, Stanford University School of Medicine, Stanford, California, United States of America
| | - Joshua A. Salomon
- Department of Health Policy, Stanford University School of Medicine, Stanford, California, United States of America
- Center for Health Policy, Freeman Spogli Institute for International Studies, Stanford University, Stanford, California, United States of America
| | - Samuel So
- Department of Surgery, Asian Liver Center, Stanford University School of Medicine, Stanford, California, United States of America
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Shiha G, Hassan A, Mousa N, El-Domiaty N, Mikhail N, Gameaa R, Kobtan A, El Bassat H, Sharaf-Eldin M, Waked I, Eslam M, Soliman R. Individualized HCC surveillance using risk stratification scores in advanced fibrosis and cirrhotic HCV patients who achieved SVR: Prospective study. Aliment Pharmacol Ther 2025; 61:99-108. [PMID: 39313490 DOI: 10.1111/apt.18291] [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: 07/10/2024] [Revised: 08/09/2024] [Accepted: 09/09/2024] [Indexed: 09/25/2024]
Abstract
BACKGROUND Several HCC risk stratification scores were developed; however, none has been prospectively validated. The primary aim is to validate the clinical utility of six HCC risk scores in large prospective study of F3-4 patients achieving SVR following DAAs according to EASL guidelines. The secondary aim is to explore whether individualized risk stratification improves detection of HCC at early stages amenable to curative treatment. METHODS This prospective study included two cohorts: Egyptian Liver Research Institute and Hospital (ELRIAH) cohort of 463 chronic HCV patients with advanced liver disease (F3 and F4) achieved SVR with a follow-up every 6 months according to EASL guidelines using 6 simple HCC risk scores and Tanta cohort of 492 comparable patients where individualized surveillance intervals were tailored based on HCC risk assessments using GES score as follows: low-risk patients were followed yearly, intermediate-risk every 6 months and high-risk every 2-3 months. RESULTS All scores, except Watanabe post, successfully stratified patients into low-, intermediate- and high-risk groups, with log-rank p-value of 0.001 and Harrell's C ranging from 0.669 to 0.728. Clinical utility of these scores revealed that the highest percentage of patients classified as low risk was 42.5% using the GES, while the lowest was 8.9% using the aMAP. ELRIAH cohort, 25 patients developed HCC with 52% diagnosed at BCLC 0 and A. Tanta cohort, 35 patients developed HCC, with 80% diagnosed at BCLC 0 and A. CONCLUSION Individualized risk stratification using HCC risk scores was associated with improved early-stage detection and receipt of curative treatment.
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Affiliation(s)
- Gamal Shiha
- Hepatology and Gastroenterology Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
- Egyptian Liver Research Institute and Hospital (ELRIAH), Mansoura, Egypt
| | - Ayman Hassan
- Egyptian Liver Research Institute and Hospital (ELRIAH), Mansoura, Egypt
- Higher Institute of Applied Medical Sciences, Mansoura, Egypt
| | - Nasser Mousa
- Tropical Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Nada El-Domiaty
- Egyptian Liver Research Institute and Hospital (ELRIAH), Mansoura, Egypt
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Nabiel Mikhail
- Egyptian Liver Research Institute and Hospital (ELRIAH), Mansoura, Egypt
- Biostatistics and Cancer Epidemiology Department, South Egypt Cancer Institute, Assiut University, Assiut, Egypt
| | - Reham Gameaa
- Tropical Medicine and Infectious Diseases Department, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Abdelrahman Kobtan
- Tropical Medicine and Infectious Diseases Department, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Hanan El Bassat
- Tropical Medicine and Infectious Diseases Department, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Mohamed Sharaf-Eldin
- Tropical Medicine and Infectious Diseases Department, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Imam Waked
- National Liver Institute, Menofia University, Menofia, Egypt
| | - Mohamed Eslam
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, New South Wales, Australia
| | - Riham Soliman
- Egyptian Liver Research Institute and Hospital (ELRIAH), Mansoura, Egypt
- Tropical Medicine Department, Faculty of Medicine, Port Said University, Port Said, Egypt
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Kamaya A, Fetzer DT, Seow JH, Burrowes DP, Choi HH, Dawkins AA, Fung C, Gabriel H, Hong CW, Khurana A, McGillen KL, Morgan TA, Sirlin CB, Tse JR, Rodgers SK. LI-RADS US Surveillance Version 2024 for Surveillance of Hepatocellular Carcinoma: An Update to the American College of Radiology US LI-RADS. Radiology 2024; 313:e240169. [PMID: 39625378 DOI: 10.1148/radiol.240169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2024]
Abstract
In 2017, the American College of Radiology introduced the US Liver Imaging Reporting and Data System (LI-RADS) as a framework for US surveillance of patients at risk for developing hepatocellular carcinoma. This has aided in the standardization of technique, clinical reporting, patient management, data collection, and research. Emerging evidence has helped inform changes to the algorithm, now released as LI-RADS US Surveillance version 2024. The updated algorithm, the rationale for changes, and its alignment with the 2023 American Association for the Study of Liver Diseases Practice Guidance are presented.
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Affiliation(s)
- Aya Kamaya
- From the Department of Radiology, Stanford University, 300 Pasteur Dr, Palo Alto, CA 94304 (A. Kamaya, J.R.T.); The University of Texas Southwestern Medical Center, Dallas, Tex (D.T.F.); Department of Radiology, Royal Perth Hospital, Perth, Western Australia, Australia (J.H.S.); Department of Radiology, University of Calgary, Calgary, Alberta, Canada (D.P.B.); Department of Radiology and Biomedical Imaging, University of California at San Francisco, San Francisco, Calif (H.H.C., C.W.H.); Department of Radiology, University of Kentucky, Lexington, Ky (A.A.D.); MIC Medical Imaging, Edmonton, Alberta, Canada (C.F.); Department of Radiology, Northwestern University, Chicago, Ill (H.G.); Department of Radiology, University of California at San Diego, UC San Diego Medical Center, San Diego, Calif (A. Khurana); Liver Imaging Group, Department of Radiology, UC San Diego, San Diego, Calif (C.B.S.); Penn State Health Milton S. Hershey Medical Center, Hershey, Pa (K.L.M.); Department of Radiology, Mayo Clinic Arizona, Phoenix, Ariz (T.A.M.); and Department of Radiology, Thomas Jefferson University, Cherry Hill, NJ (S.K.R.)
| | - David T Fetzer
- From the Department of Radiology, Stanford University, 300 Pasteur Dr, Palo Alto, CA 94304 (A. Kamaya, J.R.T.); The University of Texas Southwestern Medical Center, Dallas, Tex (D.T.F.); Department of Radiology, Royal Perth Hospital, Perth, Western Australia, Australia (J.H.S.); Department of Radiology, University of Calgary, Calgary, Alberta, Canada (D.P.B.); Department of Radiology and Biomedical Imaging, University of California at San Francisco, San Francisco, Calif (H.H.C., C.W.H.); Department of Radiology, University of Kentucky, Lexington, Ky (A.A.D.); MIC Medical Imaging, Edmonton, Alberta, Canada (C.F.); Department of Radiology, Northwestern University, Chicago, Ill (H.G.); Department of Radiology, University of California at San Diego, UC San Diego Medical Center, San Diego, Calif (A. Khurana); Liver Imaging Group, Department of Radiology, UC San Diego, San Diego, Calif (C.B.S.); Penn State Health Milton S. Hershey Medical Center, Hershey, Pa (K.L.M.); Department of Radiology, Mayo Clinic Arizona, Phoenix, Ariz (T.A.M.); and Department of Radiology, Thomas Jefferson University, Cherry Hill, NJ (S.K.R.)
| | - James H Seow
- From the Department of Radiology, Stanford University, 300 Pasteur Dr, Palo Alto, CA 94304 (A. Kamaya, J.R.T.); The University of Texas Southwestern Medical Center, Dallas, Tex (D.T.F.); Department of Radiology, Royal Perth Hospital, Perth, Western Australia, Australia (J.H.S.); Department of Radiology, University of Calgary, Calgary, Alberta, Canada (D.P.B.); Department of Radiology and Biomedical Imaging, University of California at San Francisco, San Francisco, Calif (H.H.C., C.W.H.); Department of Radiology, University of Kentucky, Lexington, Ky (A.A.D.); MIC Medical Imaging, Edmonton, Alberta, Canada (C.F.); Department of Radiology, Northwestern University, Chicago, Ill (H.G.); Department of Radiology, University of California at San Diego, UC San Diego Medical Center, San Diego, Calif (A. Khurana); Liver Imaging Group, Department of Radiology, UC San Diego, San Diego, Calif (C.B.S.); Penn State Health Milton S. Hershey Medical Center, Hershey, Pa (K.L.M.); Department of Radiology, Mayo Clinic Arizona, Phoenix, Ariz (T.A.M.); and Department of Radiology, Thomas Jefferson University, Cherry Hill, NJ (S.K.R.)
| | - David P Burrowes
- From the Department of Radiology, Stanford University, 300 Pasteur Dr, Palo Alto, CA 94304 (A. Kamaya, J.R.T.); The University of Texas Southwestern Medical Center, Dallas, Tex (D.T.F.); Department of Radiology, Royal Perth Hospital, Perth, Western Australia, Australia (J.H.S.); Department of Radiology, University of Calgary, Calgary, Alberta, Canada (D.P.B.); Department of Radiology and Biomedical Imaging, University of California at San Francisco, San Francisco, Calif (H.H.C., C.W.H.); Department of Radiology, University of Kentucky, Lexington, Ky (A.A.D.); MIC Medical Imaging, Edmonton, Alberta, Canada (C.F.); Department of Radiology, Northwestern University, Chicago, Ill (H.G.); Department of Radiology, University of California at San Diego, UC San Diego Medical Center, San Diego, Calif (A. Khurana); Liver Imaging Group, Department of Radiology, UC San Diego, San Diego, Calif (C.B.S.); Penn State Health Milton S. Hershey Medical Center, Hershey, Pa (K.L.M.); Department of Radiology, Mayo Clinic Arizona, Phoenix, Ariz (T.A.M.); and Department of Radiology, Thomas Jefferson University, Cherry Hill, NJ (S.K.R.)
| | - Hailey H Choi
- From the Department of Radiology, Stanford University, 300 Pasteur Dr, Palo Alto, CA 94304 (A. Kamaya, J.R.T.); The University of Texas Southwestern Medical Center, Dallas, Tex (D.T.F.); Department of Radiology, Royal Perth Hospital, Perth, Western Australia, Australia (J.H.S.); Department of Radiology, University of Calgary, Calgary, Alberta, Canada (D.P.B.); Department of Radiology and Biomedical Imaging, University of California at San Francisco, San Francisco, Calif (H.H.C., C.W.H.); Department of Radiology, University of Kentucky, Lexington, Ky (A.A.D.); MIC Medical Imaging, Edmonton, Alberta, Canada (C.F.); Department of Radiology, Northwestern University, Chicago, Ill (H.G.); Department of Radiology, University of California at San Diego, UC San Diego Medical Center, San Diego, Calif (A. Khurana); Liver Imaging Group, Department of Radiology, UC San Diego, San Diego, Calif (C.B.S.); Penn State Health Milton S. Hershey Medical Center, Hershey, Pa (K.L.M.); Department of Radiology, Mayo Clinic Arizona, Phoenix, Ariz (T.A.M.); and Department of Radiology, Thomas Jefferson University, Cherry Hill, NJ (S.K.R.)
| | - Adrian A Dawkins
- From the Department of Radiology, Stanford University, 300 Pasteur Dr, Palo Alto, CA 94304 (A. Kamaya, J.R.T.); The University of Texas Southwestern Medical Center, Dallas, Tex (D.T.F.); Department of Radiology, Royal Perth Hospital, Perth, Western Australia, Australia (J.H.S.); Department of Radiology, University of Calgary, Calgary, Alberta, Canada (D.P.B.); Department of Radiology and Biomedical Imaging, University of California at San Francisco, San Francisco, Calif (H.H.C., C.W.H.); Department of Radiology, University of Kentucky, Lexington, Ky (A.A.D.); MIC Medical Imaging, Edmonton, Alberta, Canada (C.F.); Department of Radiology, Northwestern University, Chicago, Ill (H.G.); Department of Radiology, University of California at San Diego, UC San Diego Medical Center, San Diego, Calif (A. Khurana); Liver Imaging Group, Department of Radiology, UC San Diego, San Diego, Calif (C.B.S.); Penn State Health Milton S. Hershey Medical Center, Hershey, Pa (K.L.M.); Department of Radiology, Mayo Clinic Arizona, Phoenix, Ariz (T.A.M.); and Department of Radiology, Thomas Jefferson University, Cherry Hill, NJ (S.K.R.)
| | - Christopher Fung
- From the Department of Radiology, Stanford University, 300 Pasteur Dr, Palo Alto, CA 94304 (A. Kamaya, J.R.T.); The University of Texas Southwestern Medical Center, Dallas, Tex (D.T.F.); Department of Radiology, Royal Perth Hospital, Perth, Western Australia, Australia (J.H.S.); Department of Radiology, University of Calgary, Calgary, Alberta, Canada (D.P.B.); Department of Radiology and Biomedical Imaging, University of California at San Francisco, San Francisco, Calif (H.H.C., C.W.H.); Department of Radiology, University of Kentucky, Lexington, Ky (A.A.D.); MIC Medical Imaging, Edmonton, Alberta, Canada (C.F.); Department of Radiology, Northwestern University, Chicago, Ill (H.G.); Department of Radiology, University of California at San Diego, UC San Diego Medical Center, San Diego, Calif (A. Khurana); Liver Imaging Group, Department of Radiology, UC San Diego, San Diego, Calif (C.B.S.); Penn State Health Milton S. Hershey Medical Center, Hershey, Pa (K.L.M.); Department of Radiology, Mayo Clinic Arizona, Phoenix, Ariz (T.A.M.); and Department of Radiology, Thomas Jefferson University, Cherry Hill, NJ (S.K.R.)
| | - Helena Gabriel
- From the Department of Radiology, Stanford University, 300 Pasteur Dr, Palo Alto, CA 94304 (A. Kamaya, J.R.T.); The University of Texas Southwestern Medical Center, Dallas, Tex (D.T.F.); Department of Radiology, Royal Perth Hospital, Perth, Western Australia, Australia (J.H.S.); Department of Radiology, University of Calgary, Calgary, Alberta, Canada (D.P.B.); Department of Radiology and Biomedical Imaging, University of California at San Francisco, San Francisco, Calif (H.H.C., C.W.H.); Department of Radiology, University of Kentucky, Lexington, Ky (A.A.D.); MIC Medical Imaging, Edmonton, Alberta, Canada (C.F.); Department of Radiology, Northwestern University, Chicago, Ill (H.G.); Department of Radiology, University of California at San Diego, UC San Diego Medical Center, San Diego, Calif (A. Khurana); Liver Imaging Group, Department of Radiology, UC San Diego, San Diego, Calif (C.B.S.); Penn State Health Milton S. Hershey Medical Center, Hershey, Pa (K.L.M.); Department of Radiology, Mayo Clinic Arizona, Phoenix, Ariz (T.A.M.); and Department of Radiology, Thomas Jefferson University, Cherry Hill, NJ (S.K.R.)
| | - Cheng William Hong
- From the Department of Radiology, Stanford University, 300 Pasteur Dr, Palo Alto, CA 94304 (A. Kamaya, J.R.T.); The University of Texas Southwestern Medical Center, Dallas, Tex (D.T.F.); Department of Radiology, Royal Perth Hospital, Perth, Western Australia, Australia (J.H.S.); Department of Radiology, University of Calgary, Calgary, Alberta, Canada (D.P.B.); Department of Radiology and Biomedical Imaging, University of California at San Francisco, San Francisco, Calif (H.H.C., C.W.H.); Department of Radiology, University of Kentucky, Lexington, Ky (A.A.D.); MIC Medical Imaging, Edmonton, Alberta, Canada (C.F.); Department of Radiology, Northwestern University, Chicago, Ill (H.G.); Department of Radiology, University of California at San Diego, UC San Diego Medical Center, San Diego, Calif (A. Khurana); Liver Imaging Group, Department of Radiology, UC San Diego, San Diego, Calif (C.B.S.); Penn State Health Milton S. Hershey Medical Center, Hershey, Pa (K.L.M.); Department of Radiology, Mayo Clinic Arizona, Phoenix, Ariz (T.A.M.); and Department of Radiology, Thomas Jefferson University, Cherry Hill, NJ (S.K.R.)
| | - Aman Khurana
- From the Department of Radiology, Stanford University, 300 Pasteur Dr, Palo Alto, CA 94304 (A. Kamaya, J.R.T.); The University of Texas Southwestern Medical Center, Dallas, Tex (D.T.F.); Department of Radiology, Royal Perth Hospital, Perth, Western Australia, Australia (J.H.S.); Department of Radiology, University of Calgary, Calgary, Alberta, Canada (D.P.B.); Department of Radiology and Biomedical Imaging, University of California at San Francisco, San Francisco, Calif (H.H.C., C.W.H.); Department of Radiology, University of Kentucky, Lexington, Ky (A.A.D.); MIC Medical Imaging, Edmonton, Alberta, Canada (C.F.); Department of Radiology, Northwestern University, Chicago, Ill (H.G.); Department of Radiology, University of California at San Diego, UC San Diego Medical Center, San Diego, Calif (A. Khurana); Liver Imaging Group, Department of Radiology, UC San Diego, San Diego, Calif (C.B.S.); Penn State Health Milton S. Hershey Medical Center, Hershey, Pa (K.L.M.); Department of Radiology, Mayo Clinic Arizona, Phoenix, Ariz (T.A.M.); and Department of Radiology, Thomas Jefferson University, Cherry Hill, NJ (S.K.R.)
| | - Kathryn L McGillen
- From the Department of Radiology, Stanford University, 300 Pasteur Dr, Palo Alto, CA 94304 (A. Kamaya, J.R.T.); The University of Texas Southwestern Medical Center, Dallas, Tex (D.T.F.); Department of Radiology, Royal Perth Hospital, Perth, Western Australia, Australia (J.H.S.); Department of Radiology, University of Calgary, Calgary, Alberta, Canada (D.P.B.); Department of Radiology and Biomedical Imaging, University of California at San Francisco, San Francisco, Calif (H.H.C., C.W.H.); Department of Radiology, University of Kentucky, Lexington, Ky (A.A.D.); MIC Medical Imaging, Edmonton, Alberta, Canada (C.F.); Department of Radiology, Northwestern University, Chicago, Ill (H.G.); Department of Radiology, University of California at San Diego, UC San Diego Medical Center, San Diego, Calif (A. Khurana); Liver Imaging Group, Department of Radiology, UC San Diego, San Diego, Calif (C.B.S.); Penn State Health Milton S. Hershey Medical Center, Hershey, Pa (K.L.M.); Department of Radiology, Mayo Clinic Arizona, Phoenix, Ariz (T.A.M.); and Department of Radiology, Thomas Jefferson University, Cherry Hill, NJ (S.K.R.)
| | - Tara A Morgan
- From the Department of Radiology, Stanford University, 300 Pasteur Dr, Palo Alto, CA 94304 (A. Kamaya, J.R.T.); The University of Texas Southwestern Medical Center, Dallas, Tex (D.T.F.); Department of Radiology, Royal Perth Hospital, Perth, Western Australia, Australia (J.H.S.); Department of Radiology, University of Calgary, Calgary, Alberta, Canada (D.P.B.); Department of Radiology and Biomedical Imaging, University of California at San Francisco, San Francisco, Calif (H.H.C., C.W.H.); Department of Radiology, University of Kentucky, Lexington, Ky (A.A.D.); MIC Medical Imaging, Edmonton, Alberta, Canada (C.F.); Department of Radiology, Northwestern University, Chicago, Ill (H.G.); Department of Radiology, University of California at San Diego, UC San Diego Medical Center, San Diego, Calif (A. Khurana); Liver Imaging Group, Department of Radiology, UC San Diego, San Diego, Calif (C.B.S.); Penn State Health Milton S. Hershey Medical Center, Hershey, Pa (K.L.M.); Department of Radiology, Mayo Clinic Arizona, Phoenix, Ariz (T.A.M.); and Department of Radiology, Thomas Jefferson University, Cherry Hill, NJ (S.K.R.)
| | - Claude B Sirlin
- From the Department of Radiology, Stanford University, 300 Pasteur Dr, Palo Alto, CA 94304 (A. Kamaya, J.R.T.); The University of Texas Southwestern Medical Center, Dallas, Tex (D.T.F.); Department of Radiology, Royal Perth Hospital, Perth, Western Australia, Australia (J.H.S.); Department of Radiology, University of Calgary, Calgary, Alberta, Canada (D.P.B.); Department of Radiology and Biomedical Imaging, University of California at San Francisco, San Francisco, Calif (H.H.C., C.W.H.); Department of Radiology, University of Kentucky, Lexington, Ky (A.A.D.); MIC Medical Imaging, Edmonton, Alberta, Canada (C.F.); Department of Radiology, Northwestern University, Chicago, Ill (H.G.); Department of Radiology, University of California at San Diego, UC San Diego Medical Center, San Diego, Calif (A. Khurana); Liver Imaging Group, Department of Radiology, UC San Diego, San Diego, Calif (C.B.S.); Penn State Health Milton S. Hershey Medical Center, Hershey, Pa (K.L.M.); Department of Radiology, Mayo Clinic Arizona, Phoenix, Ariz (T.A.M.); and Department of Radiology, Thomas Jefferson University, Cherry Hill, NJ (S.K.R.)
| | - Justin R Tse
- From the Department of Radiology, Stanford University, 300 Pasteur Dr, Palo Alto, CA 94304 (A. Kamaya, J.R.T.); The University of Texas Southwestern Medical Center, Dallas, Tex (D.T.F.); Department of Radiology, Royal Perth Hospital, Perth, Western Australia, Australia (J.H.S.); Department of Radiology, University of Calgary, Calgary, Alberta, Canada (D.P.B.); Department of Radiology and Biomedical Imaging, University of California at San Francisco, San Francisco, Calif (H.H.C., C.W.H.); Department of Radiology, University of Kentucky, Lexington, Ky (A.A.D.); MIC Medical Imaging, Edmonton, Alberta, Canada (C.F.); Department of Radiology, Northwestern University, Chicago, Ill (H.G.); Department of Radiology, University of California at San Diego, UC San Diego Medical Center, San Diego, Calif (A. Khurana); Liver Imaging Group, Department of Radiology, UC San Diego, San Diego, Calif (C.B.S.); Penn State Health Milton S. Hershey Medical Center, Hershey, Pa (K.L.M.); Department of Radiology, Mayo Clinic Arizona, Phoenix, Ariz (T.A.M.); and Department of Radiology, Thomas Jefferson University, Cherry Hill, NJ (S.K.R.)
| | - Shuchi K Rodgers
- From the Department of Radiology, Stanford University, 300 Pasteur Dr, Palo Alto, CA 94304 (A. Kamaya, J.R.T.); The University of Texas Southwestern Medical Center, Dallas, Tex (D.T.F.); Department of Radiology, Royal Perth Hospital, Perth, Western Australia, Australia (J.H.S.); Department of Radiology, University of Calgary, Calgary, Alberta, Canada (D.P.B.); Department of Radiology and Biomedical Imaging, University of California at San Francisco, San Francisco, Calif (H.H.C., C.W.H.); Department of Radiology, University of Kentucky, Lexington, Ky (A.A.D.); MIC Medical Imaging, Edmonton, Alberta, Canada (C.F.); Department of Radiology, Northwestern University, Chicago, Ill (H.G.); Department of Radiology, University of California at San Diego, UC San Diego Medical Center, San Diego, Calif (A. Khurana); Liver Imaging Group, Department of Radiology, UC San Diego, San Diego, Calif (C.B.S.); Penn State Health Milton S. Hershey Medical Center, Hershey, Pa (K.L.M.); Department of Radiology, Mayo Clinic Arizona, Phoenix, Ariz (T.A.M.); and Department of Radiology, Thomas Jefferson University, Cherry Hill, NJ (S.K.R.)
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6
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Narra K, Hull M, Teigen KJ, Reddy V, Bullock JC, Basha R, Alawi-Kakomanolis N, Gerber DE, Brown TJ. Impact of Screening on Mortality for Patients Diagnosed with Hepatocellular Carcinoma in a Safety-Net Healthcare System: An Opportunity for Addressing Disparities. Cancers (Basel) 2024; 16:3829. [PMID: 39594783 PMCID: PMC11593179 DOI: 10.3390/cancers16223829] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 11/05/2024] [Accepted: 11/12/2024] [Indexed: 11/28/2024] Open
Abstract
Purpose: We describe the impact of screening on outcomes of patients diagnosed with hepatocellular carcinoma (HCC) in an urban safety-net healthcare system compared to a non-screened cohort diagnosed with HCC. Methods: Patients diagnosed with HCC at John Peter Smith Health Network were identified by querying the hospital tumor registry and allocated to the screened cohort if they had undergone any liver imaging within one year prior to HCC diagnosis, while the remainder were allocated to the non-screened cohort. Kaplan-Meier methods and log-rank tests were used to compare 3-year survival curves from an index date of HCC diagnosis. Cox proportional hazard models were used to calculate unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). The Duffy adjustment was used to address lead-time bias. Results: A total of 158 patients were included (n = 53 screened, n = 105 non-screened). The median overall survival (OS) for the screened cohort was 19.0 months (95% CI: 9.9-NA) and that for the non-screened cohort was 5.4 months (95% CI: 3.7-8.5) [HR death (non-screened vs. screened) = 2.4, 95% CI: 1.6-3.6; log rank p < 0.0001]. The benefit of screening remained after adjusting for lead-time bias (HR 2.19, 95% CI 1.4-3.3, p = 0.0002). Conclusions: In an urban safety-net population, screening for HCC was associated with improved outcomes compared to patients diagnosed with HCC outside of a screening protocol.
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Affiliation(s)
- Kalyani Narra
- John Peter Smith Health Network, Fort Worth, TX 76104, USA
- Department of Internal Medicine, Burnett School of Medicine at Texas Christian University, Fort Worth, TX 76104, USA
| | - Madison Hull
- Texas College of Osteopathic Medicine, Fort Worth, TX 76107, USA
| | - Kari J. Teigen
- John Peter Smith Health Network, Fort Worth, TX 76104, USA
| | | | | | - Riyaz Basha
- Texas College of Osteopathic Medicine, Fort Worth, TX 76107, USA
| | - Nadia Alawi-Kakomanolis
- John Peter Smith Health Network, Fort Worth, TX 76104, USA
- Department of Internal Medicine, Burnett School of Medicine at Texas Christian University, Fort Worth, TX 76104, USA
| | - David E. Gerber
- Division of Hematology-Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
- Harold C. Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
- Peter O’Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Timothy J. Brown
- Division of Hematology-Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
- Harold C. Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
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7
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Sachar Y, Congly SE, Burak KW, Manko A, Ko HH, Ramji A, Rahman HS, Talia J, Jeyaparan J, Wong DW, Fung S, Cooper C, Kelly EM, Ma MM, Bailey R, Minuk G, Wong A, Doucette K, Elkashab M, Sebastiani G, Wong P, Coffin CS, Brahmania M. Epidemiology, Treatment Patterns and Survival in Canadian Patients With Chronic Hepatitis B-Related Hepatocellular Carcinoma. J Viral Hepat 2024; 31:739-745. [PMID: 39148449 DOI: 10.1111/jvh.13989] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Accepted: 07/17/2024] [Indexed: 08/17/2024]
Abstract
Chronic hepatitis B (CHB) is the leading cause of hepatocellular carcinoma (HCC) globally. We described and evaluated the outcomes of patients with CHB-HCC in Canada. In this retrospective cross-sectional cohort study, data were analysed from CHB mono-infected subjects seen between 1 January 2012 and 31 December 2022, and entered the Canadian Hepatitis B Network Registry. Descriptive analysis and chi-squared modelling were used to compare cohorts, followed by multivariable survival analysis regarding survival post-diagnosis. Statistical analyses were completed in R version 2.2. Of the 6711 patients with CHB who met inclusion criteria, 232 (3.5%) developed HCC. Compared with the CHB cohort, the majority of CHB-HCC cohort were male, SEA and HBeAg negative and born in endemic area (80% vs. 56%, 73% vs. 55%, 84% vs. 54%, 64% vs. 40% and all p < 0001). Overall, median HBV DNA level was log 2.54 (IQR: 0-4.04). Advanced liver disease, defined as minimum Fibrosis stage F3, was seen in 9.4% of overall cohort, but 92% of HCC cohort. At diagnosis, median tumour size was 2.5 cm (IQR: 1.7-4.0) and mean tumour number was 1.33 (SD: 1.33), with 81% of patients BCLC 0-A. Fifty-three per cent of patients were diagnosed with HCC as part of surveillance protocols. The survival rate after HCC diagnosis was 78.7%, during the median follow-up of 52.9 months (IQR: 17-90). In multivariable analysis, survival was significantly correlated with diagnosis through the screening programme. In this large cohort of patients with CHB-HCC, the majority of patients were detected with early-stage HCC and received treatment with curative intent, resulting in strong survival rates.
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Affiliation(s)
- Y Sachar
- Department of Medicine, Division of Gastroenterology and Multi-Organ Transplant Unit, London Health Sciences Center, Western University, London, Ontario, Canada
| | - S E Congly
- Cumming School of Medicine, Department of Medicine, Division of Gastroenterology and Hepatology, University of Calgary Liver Unit, Calgary, Alberta, Canada
| | - K W Burak
- Cumming School of Medicine, Department of Medicine, Division of Gastroenterology and Hepatology, University of Calgary Liver Unit, Calgary, Alberta, Canada
| | - A Manko
- Cumming School of Medicine, Department of Medicine, Division of Gastroenterology and Hepatology, University of Calgary Liver Unit, Calgary, Alberta, Canada
| | - H H Ko
- Department of Medicine, Division of Gastroenterology, University of British Columbia, Vancouver, British Columbia, Canada
| | - A Ramji
- Department of Medicine, Division of Gastroenterology, University of British Columbia, Vancouver, British Columbia, Canada
| | - H S Rahman
- Department of Medicine, Division of Gastroenterology and Multi-Organ Transplant Unit, London Health Sciences Center, Western University, London, Ontario, Canada
| | - J Talia
- Department of Medicine, Division of Gastroenterology and Multi-Organ Transplant Unit, London Health Sciences Center, Western University, London, Ontario, Canada
| | - J Jeyaparan
- Department of Medicine, Division of Gastroenterology and Multi-Organ Transplant Unit, London Health Sciences Center, Western University, London, Ontario, Canada
| | - D W Wong
- Toronto Center of Liver Medicine, Department of Medicine, Division of Gastroenterology, University of Toronto, Toronto, Ontario, Canada
| | - S Fung
- Toronto Center of Liver Medicine, Department of Medicine, Division of Gastroenterology, University of Toronto, Toronto, Ontario, Canada
| | - C Cooper
- Division of Infectious Diseases, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada
| | - E M Kelly
- Department of Medicine, Division of Gastroenterology, University of Ottawa, Ontario, Canada
| | - M M Ma
- Department of Medicine, Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada
| | - R Bailey
- Department of Medicine, Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada
| | - G Minuk
- Department of Pharmacology and Therapeutics, Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
| | - A Wong
- Department of Medicine, Division of Infectious Diseases, University of Saskatchewan, Regina, Saskatchewan, Canada
| | - K Doucette
- Department of Medicine, Division of Infectious Diseases, University of Alberta, Edmonton, Alberta, Canada
| | - M Elkashab
- Toronto Center of Liver Medicine, Department of Medicine, Division of Gastroenterology, University of Toronto, Toronto, Ontario, Canada
| | - G Sebastiani
- Department of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
| | - P Wong
- Department of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
| | - C S Coffin
- Cumming School of Medicine, Department of Medicine, Division of Gastroenterology and Hepatology, University of Calgary Liver Unit, Calgary, Alberta, Canada
| | - M Brahmania
- Cumming School of Medicine, Department of Medicine, Division of Gastroenterology and Hepatology, University of Calgary Liver Unit, Calgary, Alberta, Canada
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8
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Singal AG, Parikh ND, Kanwal F, Marrero JA, Deodhar S, Page-Lester S, Lopez C, Feng Z, Tayob N. National Liver Cancer Screening Trial (TRACER) study protocol. Hepatol Commun 2024; 8:e0565. [PMID: 39495136 PMCID: PMC11537583 DOI: 10.1097/hc9.0000000000000565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2024] [Accepted: 09/11/2024] [Indexed: 11/05/2024] Open
Abstract
BACKGROUND Professional guidelines recommend HCC screening in at-risk patients using semi-annual ultrasound with or without alpha-fetoprotein (AFP); however, this strategy has limited effectiveness due to low adherence and sensitivity. Increasing data support the potential role of blood-based biomarker panels, which could improve both aspects. The biomarker panel GALAD, comprised of sex, age, and 3 blood biomarkers (AFP, AFP-L3, and des-carboxy prothrombin des-carboxy prothrombin), has shown high sensitivity and specificity in biomarker phase II (case-control) and phase III (retrospective cohort) validation studies. However, prospective validation in a large phase IV biomarker clinical utility trial is necessary before its adoption in practice. METHODS The National Liver Cancer Screening Trial is an adaptive pragmatic randomized phase IV trial, which began enrollment in January 2024, comparing ultrasound-based versus biomarker-based screening in 5500 patients with chronic hepatitis B infection or cirrhosis from any etiology. Eligible patients are randomly assigned in a 1:1 ratio to semi-annual screening with ultrasound ± alpha-fetoprotein (arm A) or semi-annual screening with GALAD (arm B). Randomization is stratified by enrollment site, liver disease severity (per Child-Pugh class), liver disease etiology (viral, nonviral, and noncirrhotic HBV), and sex. Patients are being recruited from 15 sites (a mix of tertiary care academic referral centers, safety-net health systems, and large community health systems) over a 3-year period, and the primary endpoint, reduction in late-stage HCC, will be assessed at the end of year 5.5. DISCUSSION The results of this trial will inform the best strategy for HCC screening and early-stage detection in patients with chronic liver diseases. If GALAD shows superiority, HCC screening would primarily shift from an ultrasound-based strategy to the adoption of the biomarker panel. TRIAL REGISTRATION NCT06084234. TRIAL STATUS The TRACER Study is actively enrolling.
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Affiliation(s)
- Amit G. Singal
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Neehar D. Parikh
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Fasiha Kanwal
- Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Jorge A. Marrero
- Department of Internal Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Sneha Deodhar
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Stephanie Page-Lester
- Biostatistics Program, Public Health Science Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
| | - Camden Lopez
- Biostatistics Program, Public Health Science Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
| | - Ziding Feng
- Biostatistics Program, Public Health Science Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
| | - Nabihah Tayob
- Department of Data Science, Dana Farber Cancer Institute, Boston, Massachusetts, USA
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9
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Chai KP, Saxena V, Seo S, Horton BH, Avins AL, Sedki M, Ready JB. A Chronic Hepatitis B Identification and Surveillance Program Improves Care in an Integrated Health Plan. Am J Gastroenterol 2024:00000434-990000000-01360. [PMID: 39364887 DOI: 10.14309/ajg.0000000000003116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2024] [Accepted: 09/24/2024] [Indexed: 10/05/2024]
Abstract
INTRODUCTION Optimal management of patients with chronic hepatitis B (CHB) requires surveillance for hepatocellular carcinoma (HCC) and identification of antiviral therapy candidates, but few dedicated CHB surveillance models have been described. Kaiser Permanente Northern California developed a systematic CHB surveillance and management program in 2012. We report the results of the program's performance over the initial 8-year period. METHODS We conducted a retrospective cohort study of all patients with CHB meeting guideline criteria for HCC surveillance. Eligible patients were invited into the Kaiser Permanente Northern California Liver Care Program (LCP), wherein patients receive reminders to obtain semiannual laboratory and imaging surveillance, which are reviewed by nurse practitioners. Treatment-eligible patients are provided with antiviral medications. RESULTS Since its inception, 14,630 patients met study criteria, and 9,373 (64.1%) enrolled in the LCP. Adherence to imaging recommendations was higher in the LCP-managed group (41.5% of patients in the LCP received ≥80% of recommended imaging compared with 10.9% among patients not enrolled [risk ratio = 3.8; P < 0.001]). Approximately 63% of treatment-eligible patients in both groups received medication, although full-adherence rates were higher in patients managed in the LCP (72.3% vs 63.4%, respectively, P < 0.001). Among the 197 patients who developed HCC, recommended surveillance imaging was performed more frequently among LCP-managed patients (71.4% vs 53.8%, respectively, P < 0.05) who were also significantly more likely to be diagnosed at Barcelona Clinic Liver Cancer Stage 0/A (95.9% vs 74.6%; P < 0.001). DISCUSSION In this integrated healthcare system, a systematic program for surveilling and managing patients with CHB seemed beneficial for both process and clinical endpoints.
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Affiliation(s)
- Krisna P Chai
- Department of Gastroenterology, The Permanente Medical Group, Kaiser Permanente Northern California, Santa Clara, California, USA
| | - Varun Saxena
- Department of Gastroenterology, The Permanente Medical Group, Kaiser Permanente Northern California, South San Francisco, California, USA
- Division of Research, Kaiser Permanente Northern California, Oakland, California, USA
- Department of Gastroenterology and Transplant Hepatology, University of California San Francisco, San Francisco, California, USA
| | - Suk Seo
- Department of Gastroenterology, The Permanente Medical Group, Kaiser Permanente Northern California, Antioch, California, USA
| | - Brandon H Horton
- Division of Research, Kaiser Permanente Northern California, Oakland, California, USA
| | - Andrew L Avins
- Division of Research, Kaiser Permanente Northern California, Oakland, California, USA
| | - Mai Sedki
- Division of Research, Kaiser Permanente Northern California, Oakland, California, USA
| | - Joanna B Ready
- Department of Gastroenterology, The Permanente Medical Group, Kaiser Permanente Northern California, Santa Clara, California, USA
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10
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Sun L, Liu Z, Wu Z, Wu Z, Qiu B, Liu S, Hu J, Yin X. PSMD11 promotes the proliferation of hepatocellular carcinoma by regulating the ubiquitination degradation of CDK4. Cell Signal 2024; 121:111279. [PMID: 38944255 DOI: 10.1016/j.cellsig.2024.111279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 06/14/2024] [Accepted: 06/26/2024] [Indexed: 07/01/2024]
Abstract
BACKGROUND The 26S proteasome non-ATPase regulatory subunit 11 is a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins, and PSMD11 plays a key role in the regulation of embryonic stem cell proteasome activity. However, the role of PSMD11 in hepatocellular carcinoma has not been studied. In this study, it was found that the expression of PSMD11 in HCC tissues was significantly higher than that in para-cancerous tissues, and was associated with poor prognosis. The results of in vitro experiments showed that PSMD11 knockdown could effectively inhibit the proliferation and apoptosis of hepatoma cell lines, and flow cytometry showed that the G0/G1 phase was significantly prolonged. Through protein spectrometry, immunoprecipitation and in vitro experiments, it was found that PSMD11 can promote the proliferation of hepatocellular carcinoma through regulating the ubiquitination of CDK4 and enhancing its protein stability. This study explores the mechanism of action of PSMD11 in hepatocellular carcinoma and provides new insights for the treatment of hepatocellular carcinoma.
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Affiliation(s)
- Liang Sun
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Zitao Liu
- Department of Gastrointestinal Surgery, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Zhengyi Wu
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Zhipeng Wu
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Bingbing Qiu
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Shuiqiu Liu
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Junwen Hu
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
| | - Xiangbao Yin
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
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11
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Salehi MA, Harandi H, Mohammadi S, Shahrabi Farahani M, Shojaei S, Saleh RR. Diagnostic Performance of Artificial Intelligence in Detection of Hepatocellular Carcinoma: A Meta-analysis. JOURNAL OF IMAGING INFORMATICS IN MEDICINE 2024; 37:1297-1311. [PMID: 38438694 PMCID: PMC11300422 DOI: 10.1007/s10278-024-01058-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Revised: 02/18/2024] [Accepted: 02/19/2024] [Indexed: 03/06/2024]
Abstract
Due to the increasing interest in the use of artificial intelligence (AI) algorithms in hepatocellular carcinoma detection, we performed a systematic review and meta-analysis to pool the data on diagnostic performance metrics of AI and to compare them with clinicians' performance. A search in PubMed and Scopus was performed in January 2024 to find studies that evaluated and/or validated an AI algorithm for the detection of HCC. We performed a meta-analysis to pool the data on the metrics of diagnostic performance. Subgroup analysis based on the modality of imaging and meta-regression based on multiple parameters were performed to find potential sources of heterogeneity. The risk of bias was assessed using Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) and Prediction Model Study Risk of Bias Assessment Tool (PROBAST) reporting guidelines. Out of 3177 studies screened, 44 eligible studies were included. The pooled sensitivity and specificity for internally validated AI algorithms were 84% (95% CI: 81,87) and 92% (95% CI: 90,94), respectively. Externally validated AI algorithms had a pooled sensitivity of 85% (95% CI: 78,89) and specificity of 84% (95% CI: 72,91). When clinicians were internally validated, their pooled sensitivity was 70% (95% CI: 60,78), while their pooled specificity was 85% (95% CI: 77,90). This study implies that AI can perform as a diagnostic supplement for clinicians and radiologists by screening images and highlighting regions of interest, thus improving workflow.
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Affiliation(s)
| | - Hamid Harandi
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Research Center for Antibiotic Stewardship and Antimicrobial Resistance, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Soheil Mohammadi
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
| | | | - Shayan Shojaei
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Ramy R Saleh
- Department of Oncology, McGill University, Montreal, QC, H3A 0G4, Canada
- Division of Medical Oncology, McGill University Health Centre, Montreal, QC, H4A 3J1, Canada
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12
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Amador A, Salord S, Xiol X, Garcia-Guix M, Cachero A, Rota R, Hernandez Aretxabaleta N, Baliellas C, Castellote J. Improvement of quality of care provided to outpatients with hepatic cirrhosis after an educational intervention. Eur J Gastroenterol Hepatol 2024; 36:941-944. [PMID: 38625820 DOI: 10.1097/meg.0000000000002778] [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] [Indexed: 04/18/2024]
Abstract
OBJECTIVE A set of indicators has been reported to measure the quality of care for cirrhotic patients, and previously published studies report variable adherence rates to these indicators. This study aimed to assess the quality of care provided to cirrhotic outpatients before and after an educational intervention by determining its impact on adherence to quality indicators. METHODS We conducted a quasi-experimental, cross-sectional study including 324 cirrhotic patients seen in 2017 and 2019 at a tertiary teaching hospital in Spain. Quality indicators were assessed in five domains: documentation of cirrhosis etiology, disease severity assessment, hepatocellular carcinoma (HCC) screening, variceal bleeding prophylaxis, and vaccination. After identifying areas for improvement, an educational intervention was implemented. A second evaluation was performed after the intervention to assess changes in adherence rates. RESULTS Before the intervention, adherence rates were excellent (>90%) for indicators related to variceal bleeding prophylaxis and documentation of cirrhosis etiology, acceptable (60-80%) for HCC screening and disease severity assessment, and poor (<50%) for vaccinations. After the educational intervention, there was a statistically significant improvement in adherence rates for eight indicators related to HCC screening (70-90%), disease severity assessment (90%), variceal bleeding prophylaxis (>90%), and vaccinations (60-90%). CONCLUSION Our study demonstrates a significant improvement in the quality of care provided to cirrhotic outpatients after an educational intervention. The findings highlight the importance of targeted educational interventions to enhance adherence to quality indicators in the management of cirrhosis.
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Affiliation(s)
- Alberto Amador
- Hepatology Unit, Gastroenterology Department, Hospital Universitari de Bellvitge, Institut Català de la Salut, Hepatobiliary and Pancreatic Diseases Research Group, IDIBELL, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain
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13
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Mendiratta-Lala M, Fetzer D, Kamaya A, Parikh ND, Singal AG. The Future Role of Abdominal US in Hepatocellular Carcinoma Surveillance. Radiology 2024; 311:e232624. [PMID: 38742973 PMCID: PMC11140528 DOI: 10.1148/radiol.232624] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Revised: 12/16/2023] [Accepted: 12/26/2023] [Indexed: 05/16/2024]
Abstract
Abdominal US is currently the best-validated surveillance strategy for hepatocellular carcinoma (HCC) in at-risk patients. It is the only modality shown to have completed all five phases of validation and can achieve high sensitivity and specificity for HCC detection, especially when conducted by expert sonographers in high-volume centers. However, US also has limitations, including operator dependency and varying sensitivity in clinical practice. Further, the sensitivity of US for early-stage HCC detection is lower in patients with obesity or nonviral liver disease, increasingly common populations undergoing surveillance. Imaging-based and blood-based surveillance strategies, including abbreviated MRI and biomarker panels, may overcome some limitations of US-based surveillance. Both strategies have promising test performance in phase II and phase III biomarker studies and are undergoing prospective validation. Considering the variation in HCC risk and test performance between patients, there will likely be a shift away from a one-size-fits-all approach and toward precision screening, in which the "best" test is selected based on individual patient characteristics. In this upcoming era of precision HCC screening among patients with cirrhosis, US will likely continue to have an important, albeit reduced, surveillance role.
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Affiliation(s)
| | | | - Aya Kamaya
- From the Departments of Radiology (M.M.L.) and Internal Medicine
(N.D.P.), University of Michigan, Ann Arbor, Mich; Department of Radiology
(D.F.) and Department of Internal Medicine, Division of Digestive and Liver
Diseases (A.G.S.), University of Texas Southwestern Medical Center, 5959 Harry
Hines Blvd, Ste 420, POB 1, Dallas, TX 75390-8887; and Department of Radiology,
Stanford University School of Medicine, Stanford, Calif (A.K.)
| | - Neehar D. Parikh
- From the Departments of Radiology (M.M.L.) and Internal Medicine
(N.D.P.), University of Michigan, Ann Arbor, Mich; Department of Radiology
(D.F.) and Department of Internal Medicine, Division of Digestive and Liver
Diseases (A.G.S.), University of Texas Southwestern Medical Center, 5959 Harry
Hines Blvd, Ste 420, POB 1, Dallas, TX 75390-8887; and Department of Radiology,
Stanford University School of Medicine, Stanford, Calif (A.K.)
| | - Amit G. Singal
- From the Departments of Radiology (M.M.L.) and Internal Medicine
(N.D.P.), University of Michigan, Ann Arbor, Mich; Department of Radiology
(D.F.) and Department of Internal Medicine, Division of Digestive and Liver
Diseases (A.G.S.), University of Texas Southwestern Medical Center, 5959 Harry
Hines Blvd, Ste 420, POB 1, Dallas, TX 75390-8887; and Department of Radiology,
Stanford University School of Medicine, Stanford, Calif (A.K.)
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14
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Ullah Khan N, Sadiq A, Khan J, Basharat N, Hassan ZU, Ali I, Shah TA, Bourhia M, Bin Jardan YA, Wondmie GF. Molecular characterization of plasma virome of hepatocellular carcinoma (HCC) patients. AMB Express 2024; 14:46. [PMID: 38664337 PMCID: PMC11045709 DOI: 10.1186/s13568-024-01696-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Accepted: 04/09/2024] [Indexed: 04/28/2024] Open
Abstract
Hepatocellular carcinoma (HCC) stands as the most common cancer type, arising from various causes, and responsible for a substantial number of cancer-related fatalities. Recent advancements in viral metagenomics have empowered scientists to delve into the intricate diversity of the virosphere, viral evolution, interactions between viruses and their hosts, and the identification of viral causes behind disease outbreaks, the development of specific symptoms, and their potential role in altering the host's physiology. The present study had the objective of "Molecular Characterization of HBV, HCV, anelloviruses, CMV, SENV-D, SENV-H, HEV, and HPV viruses among individuals suffering from HCC." A total of 381 HCC patients contributed 10 cc of blood each for this study. The research encompassed the assessment of tumor markers, followed by molecular characterization of HBV, HCV, Anelloviruses (TTV, TTMV, and TTMDV), SENV-H and SENV-D viruses, HEV, CMV, and HPV, as well as histopathological examinations. The outcomes of this study revealed that majority of the HCC patients 72.4% (276/381) were male as compared to females. HCV infection, at 76.4% (291 out of 381), exhibited a significant association (p < 0.05) with HCC. Most patients displayed singular lesions in the liver, with Child Pugh Score Type B being the predominant finding in 45.2% of cases. Plasma virome analysis indicated the prevalence of TTMDV (75%), followed by TTMV (70%) and TTV (42.1%) among anelloviruses in HCC patients. Similarly, SENV-H (52%) was followed by SENV-D (20%), with co-infections at 15%. The presence of CMV and HEV among the HCC patients was recorded 5% each however 3.5% of the patients showed the presence of HPV. In conclusion, this study underscores that HCC patients serve as reservoirs for various pathogenic and non-pathogenic viruses, potentially contributing to the development, progression, and severity of the disease.
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Affiliation(s)
- Niamat Ullah Khan
- Molecular Virology Laboratory, Department of Biosciences, COMSATS University, Islamabad, Pakistan
| | - Asma Sadiq
- Department of Microbiology, University of Jhang, Punjab, Pakistan
| | - Jadoon Khan
- Molecular Virology Laboratory, Department of Biosciences, COMSATS University, Islamabad, Pakistan.
- Department of Allied Health Sciences, Iqra University, Chak Shahzad Campus, Islamabad, Pakistan.
| | - Nosheen Basharat
- Department of Microbiology, University of Jhang, Punjab, Pakistan
| | - Zulfiqar Ul Hassan
- Department of Allied Health Sciences, Iqra University, Chak Shahzad Campus, Islamabad, Pakistan
| | - Ijaz Ali
- Molecular Virology Laboratory, Department of Biosciences, COMSATS University, Islamabad, Pakistan
- Center for Applied Mathematics and Bioinformatics (CAMB), Gulf University for Science and Technology, West Mishref, Kuwait
| | - Tawaf Ali Shah
- College of Agriculture Engineering and Food Science, Shandong University of Technology, Zibo, 255000, China
| | - Mohammed Bourhia
- Laboratory of Biotechnology and Natural Resources Valorization, Faculty of Sciences, Ibn Zohr University, Agadir, 80060, Morocco.
| | - Yousef A Bin Jardan
- Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 11451, Riyadh, Saudi Arabia
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Hazari Y, Chevet E, Bailly-Maitre B, Hetz C. ER stress signaling at the interphase between MASH and HCC. Hepatology 2024:01515467-990000000-00844. [PMID: 38626349 DOI: 10.1097/hep.0000000000000893] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2024] [Accepted: 03/28/2024] [Indexed: 04/18/2024]
Abstract
HCC is the most frequent primary liver cancer with an extremely poor prognosis and often develops on preset of chronic liver diseases. Major risk factors for HCC include metabolic dysfunction-associated steatohepatitis, a complex multifactorial condition associated with abnormal endoplasmic reticulum (ER) proteostasis. To cope with ER stress, the unfolded protein response engages adaptive reactions to restore the secretory capacity of the cell. Recent advances revealed that ER stress signaling plays a critical role in HCC progression. Here, we propose that chronic ER stress is a common transversal factor contributing to the transition from liver disease (risk factor) to HCC. Interventional strategies to target the unfolded protein response in HCC, such as cancer therapy, are also discussed.
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Affiliation(s)
- Younis Hazari
- Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile
- Faculty of Medicine, Biomedical Neuroscience Institute (BNI), University of Chile, Santiago, Chile
- Center for Geroscience, Brain Health and Metabolism (GERO), Santiago, Chile
- Department of Biotechnology, University of Kashmir, Srinagar, India
| | - Eric Chevet
- Inserm U1242, University of Rennes, Rennes, France
- Centre de Lutte Contre le Cancer Eugène Marquis, Rennes, France
| | - Béatrice Bailly-Maitre
- Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1065, Université Côte d'Azur (UCA), Centre Méditerranéen de Médecine Moléculaire (C3M), 06204 Nice, France Team "Metainflammation and Hematometabolism", Metabolism Department, France
- Université Côte d'Azur, INSERM, U1065, C3M, 06200 Nice, France
| | - Claudio Hetz
- Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile
- Faculty of Medicine, Biomedical Neuroscience Institute (BNI), University of Chile, Santiago, Chile
- Center for Geroscience, Brain Health and Metabolism (GERO), Santiago, Chile
- Buck Institute for Research on Aging, Novato, California, USA
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16
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Donati A, Henrion J, Regnier M, Deltenre P, Marot A. Abstinence is associated with better outcomes in patients with alcohol-related hepatocellular carcinoma: Results of an observational study. Clin Res Hepatol Gastroenterol 2023; 47:102225. [PMID: 37838325 DOI: 10.1016/j.clinre.2023.102225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 10/04/2023] [Accepted: 10/11/2023] [Indexed: 10/16/2023]
Abstract
BACKGROUND Patients with alcohol-related cirrhosis and hepatocellular carcinoma (HCC) may have reduced survival compared to those with HCC related to other causes. The impact of abstinence in alcohol-related HCC is unknown. We compared access to curative treatment and the prognosis of patients with HCC according to the cause of cirrhosis and evaluated the impact of abstinence on the prognosis of patients with alcohol-related HCC. PATIENTS AND METHODS Data for patients with cirrhosis and HCC were prospectively collected in a single center. A logistic regression model was used to identify factors associated with access to curative treatment. Multivariate Fine and Gray proportional hazards models were used to identify factors associated with 5-year survival after adjustment for lead-time bias. RESULTS Two hundred patients were included, 114 (57 %) with non-alcohol-related HCC and 86 (43 %) with alcohol-related HCC (35 abstainers, 51 consumers). During follow-up, 21 patients were transplanted and 156 died. The proportion of patients who had access to curative treatment was 65 % in abstainers, 44 % in consumers, and 57 % in patients with non-alcohol-related cirrhosis (p = 0.06). In multivariate analyses, abstinence was not associated with better access to curative treatment. After adjustment for lead-time bias, the 5-year cumulative incidence of overall death was significantly lower in abstainers than in consumers and in patients with non-alcohol-related cirrhosis (52 % vs. 78 % vs. 81 %, respectively, p = 0.04). In multivariate analyses, abstainers had lower risk of death than consumers (SHR: 0.47, 95 % CI: 0.28-0.80, p = 0.005). CONCLUSION Abstinence improves the outcome of patients with alcohol-related cirrhosis once HCC has occurred.
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Affiliation(s)
- Adeline Donati
- Department of Gastroenterology and Hepatology, CHU UCL Namur, Université Catholique de Louvain, Avenue G. Therasse, 1, Yvoir 5530, Belgium
| | - Jean Henrion
- Department of Gastroenterology and Hepatology, Hôpital de Jolimont, Haine-Saint-Paul, Belgium
| | - Maxime Regnier
- Scientific Support Unit (USS), CHU UCL Namur, Université Catholique de Louvain, Yvoir, Belgium
| | - Pierre Deltenre
- Department of Gastroenterology and Hepatology, CHU UCL Namur, Université Catholique de Louvain, Avenue G. Therasse, 1, Yvoir 5530, Belgium; Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium; Department of Gastroenterology and Hepatology, Clinique St Luc, Bouge, Belgium
| | - Astrid Marot
- Department of Gastroenterology and Hepatology, CHU UCL Namur, Université Catholique de Louvain, Avenue G. Therasse, 1, Yvoir 5530, Belgium.
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17
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Yang J, Yang Z, Zeng X, Yu S, Gao L, Jiang Y, Sun F. Benefits and harms of screening for hepatocellular carcinoma in high-risk populations: systematic review and meta-analysis. JOURNAL OF THE NATIONAL CANCER CENTER 2023; 3:175-185. [PMID: 39035193 PMCID: PMC11256723 DOI: 10.1016/j.jncc.2023.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 12/30/2022] [Accepted: 02/03/2023] [Indexed: 12/05/2023] Open
Abstract
OBJECTIVE The incidence and mortality of hepatocellular carcinoma (HCC) have been increasing around the world. Current guidelines recommend HCC screening in high-risk population. However, the strength of evidence of benefits and harms of HCC screening to support the recommendation was unclear. The objective is to systematically synthesize current evidence on the benefits and harms of HCC screening. METHODS We searched PubMed and nine other databases until August 20, 2021. We included cohort studies and RCTs that compared the benefits and harms of screening and non-screening in high-risk population of HCC. Case series studies that reported harms of HCC screening were also included. Pooled risk ratio (RR), according to HCC screening status, was calculated for each benefit outcome (e.g., HCC mortality, survival rate, proportion of early HCC), using head-to-head meta-analysis. The harmful outcomes (e.g., proportion of physiological harms provided by non-comparative studies were pooled by prevalence of meta-analysis. Analysis on publication bias and quality of life, subgroup analysis, and sensitivity analysis were also conducted. RESULTS We included 70 studies, including four random clinical trials (RCTs), 63 cohort studies,three case series studies. The meta-analysis of RCTs showed HCC screening was significantly associated with reduced HCC mortality (RR [risk ratio], 0.73 [95% CI, 0.56-0.96]; I 2 = 75.1%), prolonged overall survival rates (1-year, RR, 1.72 [95% CI, 1.13-2.61]; I 2 = 72.5%; 3-year, RR, 2.86 [95% CI, 1.78-4.58]; I 2 = 10.1%; and 5-year, RR, 2.76 [95% CI, 1.37-5.54]; I 2 = 28.3%), increased proportion of early HCC detection (RR, 2.68 [95% CI, 1.77-4.06]; I 2 = 50.4%). Similarly, meta-analysis of cohort studies indicated HCC screening was more effective than non-screening. However, pooled proportion of physiological harms was 16.30% (95% CI: 8.92%-23.67%) and most harms were of a mild to moderate severity. CONCLUSION The existing evidence suggests HCC screening is more effective than non-screening in high-risk population. However, harms of screening should not be ignored.
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Affiliation(s)
- Jichun Yang
- Department of Epidemiology and Biostatistics, School of Population Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - Zhirong Yang
- Primary Care Unit, School of Clinical Medicine, University of Cambridge, Cambridgeshire, UK
- Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
| | - Xueyang Zeng
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - Shuqing Yu
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - Le Gao
- Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
| | - Yu Jiang
- Department of Epidemiology and Biostatistics, School of Population Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Feng Sun
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
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18
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Zeng H, Cao M, Xia C, Wang D, Chen K, Zhu Z, Fu R, Zhang S, Zhou J, Wang H, Qi X, Dai S, Chen Y, Sun Z, Ding H, Li Q, Zhao H, Zhang X, Morze J, Ji JS, Sun F, Yu X, Qu C, Chen W. Performance and effectiveness of hepatocellular carcinoma screening in individuals with HBsAg seropositivity in China: a multicenter prospective study. NATURE CANCER 2023; 4:1382-1394. [PMID: 37667043 DOI: 10.1038/s43018-023-00618-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/05/2023] [Accepted: 07/19/2023] [Indexed: 09/06/2023]
Abstract
Current guidelines recommend hepatocellular carcinoma (HCC) surveillance for at-risk individuals, including individuals with hepatitis B virus infection. However, the performance and survival benefits of annual screening have not been evaluated through multicenter prospective studies in a Chinese population. Between 2017 and 2021, we included 14,426 participants with hepatitis B surface antigen seropositivity in an annual HCC screening study in China using a multicenter prospective design with ultrasonography and serum alpha-fetoprotein. After four rounds of screening and follow-up, the adjusted hazard ratios of death after correction for lead-time and length-time biases for screen-detected cancers at the prevalent and incident rounds were 0.74 (95% confidence interval = 0.60-0.91) and 0.52 (95% confidence interval = 0.40-0.68), respectively. A meta-analysis demonstrated that HCC screening was associated with improved survival after adjusting for lead-time bias. Our findings highlight the 'real-world' feasibility and effectiveness of annual HCC screening in community settings for the early detection of HCC and to improve survival.
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Affiliation(s)
- Hongmei Zeng
- National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Maomao Cao
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Changfa Xia
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Dongmei Wang
- State Key Laboratory of Molecular Oncology and Department of Immunology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Kun Chen
- State Key Laboratory of Molecular Oncology and Department of Immunology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Zheng Zhu
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Ruiying Fu
- National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Shaokai Zhang
- Department of Cancer Epidemiology, Affiliated Cancer Hospital of Zhengzhou University/Henan Cancer Hospital, Henan Engineering Research Center of Cancer Prevention and Control, Henan International Joint Laboratory of Cancer Prevention, Zhengzhou, People's Republic of China
| | - Jinyi Zhou
- Department for Chronic Non-communicable Diseases Control, Jiangsu Provincial Center for Disease Control and Prevention (Public Health Research Institute of Jiangsu Province), Nanjing, People's Republic of China
| | - Huadong Wang
- Department of Chronic Non-communicable Diseases Prevention and Treatment, Anhui Provincial Center for Disease Control and Prevention, Hefei, People's Republic of China
| | - Xianyun Qi
- Department of Chronic Non-communicable Diseases Prevention and Treatment, Yingdong Center for Disease Control and Prevention, Fuyang, People's Republic of China
| | - Shuguang Dai
- Sheyang Center for Disease Control and Prevention, Yancheng, People's Republic of China
| | - Yong Chen
- Binhai Center for Disease Control and Prevention, Yancheng, People's Republic of China
| | - Zhong Sun
- Dancheng Center for Disease Control and Prevention, Zhoukou, People's Republic of China
| | - Hao Ding
- Mengcheng Center for Disease Control and Prevention, Bozhou, People's Republic of China
| | - Qingwen Li
- Shenqiu Center for Disease Control and Prevention, Zhoukou, People's Republic of China
| | - Hui Zhao
- Lingbi Center for Disease Control and Prevention, Suzhou, People's Republic of China
| | - Xuehong Zhang
- Department of Nutrition, Harvard University, Cambridge, MA, USA
| | - Jakub Morze
- Department of Cardiology and Internal Medicine, College of Medical Sciences, SGMK University, Olsztyn, Poland
| | - John S Ji
- Vanke School of Public Health, Tsinghua University, Beijing, People's Republic of China
| | - Feng Sun
- Department of Epidemiology and Biostatistics, Peking University, Beijing, People's Republic of China
| | - Xueqin Yu
- The Daffodil Centre, The University of Sydney, Sydney, New South Wales, Australia
| | - Chunfeng Qu
- State Key Laboratory of Molecular Oncology and Department of Immunology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
| | - Wanqing Chen
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
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19
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Fukushima T, Morimoto M, Kobayashi S, Ueno M, Uojima H, Hidaka H, Kusano C, Chuma M, Numata K, Tsuruya K, Arase Y, Kagawa T, Hattori N, Ikeda H, Watanabe T, Tanaka K, Maeda S. Association Between Immune-Related Adverse Events and Survival in Patients with Hepatocellular Carcinoma Treated With Atezolizumab Plus Bevacizumab. Oncologist 2023; 28:e526-e533. [PMID: 37023703 PMCID: PMC10322131 DOI: 10.1093/oncolo/oyad090] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Accepted: 03/09/2023] [Indexed: 04/08/2023] Open
Abstract
BACKGROUND Immune checkpoint inhibitors (ICIs) are effective for advanced hepatocellular carcinoma (HCC). However, there are few reports on the correlation between the clinical efficacy of ICIs and the development of immune-related adverse events (irAEs) in patients with HCC. The aim of this study was to investigate the association between irAE development and survival in patients with HCC treated with atezolizumab plus bevacizumab. PATIENTS AND METHODS We enrolled 150 patients with advanced HCC treated with atezolizumab plus bevacizumab between October 2020 and October 2021 at 5 territorial institutions. We compared the efficacy of atezolizumab plus bevacizumab between patients who experienced irAEs (irAE group) and those who did not (non-irAE group). RESULTS Thirty-two patients (21.3%) developed irAEs of any grade. Grade 3/4 irAEs were observed in 9 patients (6.0%). The median progression-free survivals (PFS) in the irAE and non-irAE groups were 273 and 189 days, respectively (P = .055). The median overall survivals (OS) in the irAE and non-irAE groups were not reached and 458 days, respectively (P = .036). Grade 1/2 irAEs significantly prolonged PFS (P = .014) and OS (P = .003). Grade 1/2 irAEs were significantly associated with PFS (hazard ratio [HR], 0.339; 95% confidence interval [CI], 0.166-0.691; P = .003) and OS (HR, 0.086; 95% CI, 0.012-0.641; P = .017) on multivariate analysis. CONCLUSION The development of irAEs was associated with increased survival in a real-world population of patients with advanced HCC treated with atezolizumab plus bevacizumab. Grade 1/2 irAEs were strongly correlated with PFS and OS.
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Affiliation(s)
- Taito Fukushima
- Division of Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center, Yokohama, Japan
| | - Manabu Morimoto
- Division of Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center, Yokohama, Japan
| | - Satoshi Kobayashi
- Division of Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center, Yokohama, Japan
| | - Makoto Ueno
- Division of Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center, Yokohama, Japan
| | - Haruki Uojima
- Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan
| | - Hisashi Hidaka
- Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan
| | - Chika Kusano
- Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan
| | - Makoto Chuma
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Kazushi Numata
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Kota Tsuruya
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan
| | - Yoshitaka Arase
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan
| | - Tatehiro Kagawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan
| | - Nobuhiro Hattori
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Hiroki Ikeda
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Tsunamasa Watanabe
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Katsuaki Tanaka
- Gastroenterology Division, Hadano Red Cross Hospital, Hadano, Japan
| | - Shin Maeda
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
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20
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Zhang YH, Chen XL, Wang YR, Hou YW, Zhang YD, Wang KJ. Prevention of malignant digestive system tumors should focus on the control of chronic inflammation. World J Gastrointest Oncol 2023; 15:389-404. [PMID: 37009320 PMCID: PMC10052658 DOI: 10.4251/wjgo.v15.i3.389] [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: 10/28/2022] [Revised: 01/17/2023] [Accepted: 02/07/2023] [Indexed: 03/14/2023] Open
Abstract
Chronic inflammation, through a variety of mechanisms, plays a key role in the occurrence and development of digestive system malignant tumors (DSMTs). In this study, we feature and provide a comprehensive understanding of DSMT prevention strategies based on preventing or controlling chronic inflammation. The development and evaluation of cancer prevention strategies is a longstanding process. Cancer prevention, especially in the early stage of life, should be emphasized throughout the whole life course. Issues such as the time interval for colon cancer screening, the development of direct-acting antiviral drugs for liver cancer, and the Helicobacter pylori vaccine all need to be explored in long-term, large-scale experiments in the future.
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Affiliation(s)
- Yue-Hua Zhang
- College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- Henan International Joint Laboratory of Prevention and Treatment of Pediatric Diseases, Henan Children's Hospital Zhengzhou Children’s Hospital, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450018, Henan Province, China
| | - Xiao-Lin Chen
- Department of Prenatal Diagnosis Center, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Yi-Ran Wang
- Henan International Joint Laboratory of Prevention and Treatment of Pediatric Diseases, Henan Children's Hospital Zhengzhou Children’s Hospital, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450018, Henan Province, China
| | - Yu-Wei Hou
- Henan International Joint Laboratory of Prevention and Treatment of Pediatric Diseases, Henan Children's Hospital Zhengzhou Children’s Hospital, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450018, Henan Province, China
| | - Yao-Dong Zhang
- Henan International Joint Laboratory of Prevention and Treatment of Pediatric Diseases, Henan Children's Hospital Zhengzhou Children’s Hospital, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450018, Henan Province, China
| | - Kai-Juan Wang
- Henan International Joint Laboratory of Prevention and Treatment of Pediatric Diseases, Henan Children's Hospital Zhengzhou Children’s Hospital, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450018, Henan Province, China
- Henan Children’s Hospital Zhengzhou Children’s Hospital, Children’s Hospital Affiliated to Zhengzhou University, Key Laboratory of Tumor Epidemiology of Henan Province, State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou 450001, Henan Province, China
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An Overview of Hepatocellular Carcinoma Surveillance Focusing on Non-Cirrhotic NAFLD Patients: A Challenge for Physicians. Biomedicines 2023; 11:biomedicines11020586. [PMID: 36831120 PMCID: PMC9953185 DOI: 10.3390/biomedicines11020586] [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: 01/14/2023] [Revised: 02/08/2023] [Accepted: 02/09/2023] [Indexed: 02/18/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide and it ranges from simple steatosis to hepatocellular carcinoma (HCC). HCC represents the first liver tumor and the third source of cancer death. In the next few years, the prevalence of NAFLD and consequently of HCC is estimated to increase, becoming a major public health problem. The NAFLD-HCC shows several differences compared to other causes of chronic liver disease (CLD), including the higher percentage of patients that develop HCC in the absence of liver cirrhosis. In HCC surveillance, the international guidelines suggest a six months abdominal ultrasound (US), with or without alpha-fetoprotein (AFP) evaluation, in patients with cirrhosis and in a subgroup of patients with chronic hepatitis B infection. However, this screening program reveals several limitations, especially in NAFLD patients. Thus, new biomarkers and scores have been proposed to overcome the limits of HCC surveillance. In this narrative review we aimed to explore the differences in the HCC features between NAFLD and non-NAFLD patients, and those between NAFLD-HCC developed in the cirrhotic and non-cirrhotic liver. Finally, we focused on the limits of tumor surveillance in NAFLD patients, and we explored the new biomarkers for the early diagnosis of HCC.
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Ramai D, Singh J, Chandan S, Tartaglia N, Ambrosi A, Khan SR, Sacco R, Facciorusso A. 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] [MESH Headings] [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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Affiliation(s)
- Daryl Ramai
- Division of Gastroenterology and Hepatology, University of Utah, Salt Lake City, UT
| | - Jameel Singh
- Department of Internal Medicine, Mather Hospital, Northwell Health, Port Jefferson, NY
| | - Saurabh Chandan
- Division of Gastroenterology & Hepatology, CHI Health Creighton University Medical Center, Omaha, NE
| | - Nicola Tartaglia
- Department of Surgical and Medical Sciences, General Surgery Unit
| | - Antonio Ambrosi
- Department of Surgical and Medical Sciences, General Surgery Unit
| | - Shahab R Khan
- Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Rodolfo Sacco
- Section of Internal Medicine, Hospital of Faenza, Faenza, Italy
| | - Antonio Facciorusso
- Section of Gastroenterology, Department of Surgical and Medical Sciences, University of Foggia, Foggia
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23
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Yu CY, Huang PH, Tsang LLC, Hsu HW, Lim WX, Weng CC, Huang TL, Hsu CC, Chen CL, Ou HY, Cheng YF. Yttrium-90 Radioembolization as the Major Treatment of Hepatocellular Carcinoma. J Hepatocell Carcinoma 2023; 10:17-26. [PMID: 36660410 PMCID: PMC9843618 DOI: 10.2147/jhc.s385478] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Accepted: 01/04/2023] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND The purpose of this study was to assess the safety and efficacy of Yttrium-90 radioembolization using in unresectable hepatocellular carcinoma. METHODS From 2017 to 2021, 32 patients with unresectable hepatocellular carcinoma, with mean tumor diameter about 7cm (21 males, 11 females; median age, 57.5 years of age), treated with Yttrium-90 radioembolization using resin microspheres were reviewed at pre-Yttrium-90 and post-Yttrium-90 follow-up. Tumor response was assessed according to the modified Response Evaluation Criteria in Solid Tumors. Outcomes including overall survival and progression-free survival were reported. RESULTS Median follow-up was 18 months. At follow-up examinations at 3-, 6-, and 12-months follow-up, the overall survival rates were 94%, 87% and 59%, and the progression-free survival rates were 78%, 64% and 60%, respectively. Complete response, partial response, stable disease, and progressive disease were noted in 7 (21.9%), 14 (43.7%), 4 (12.5%), and 7 (21.9%) patients, respectively. The disease control rate was 78.1%, the objective response rate was 65.6%, and the successful downstage rate was 34.4% (11 of 32). Nine of thirty-two patients underwent resection or transplantation after Yttrium-90 radioembolization with 2-year overall survival being 100%. No serious adverse events occurred after Yttrium-90 treatment. Worse overall survival was related to the larger tumor, higher stage, Eastern Cooperative Oncology Group performance status, and Child-Pugh score. And worse progression-free survival was related to the higher tumor burden, and pre-Yttrium-90 serum α-fetoprotein level >100. CONCLUSION Yttrium-90 Radioembolization can control hepatocellular carcinoma well even in advanced diseases. Patients successfully downstaging/bridging to resection or transplantation have excellent overall survival.
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Affiliation(s)
- Chun-Yen Yu
- Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Po-Hsun Huang
- Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Leo Leung-Chit Tsang
- Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Hsien-Wen Hsu
- Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Wei-Xiong Lim
- Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ching-Chun Weng
- Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Tung-Liang Huang
- Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chien-Chin Hsu
- Department of Nuclear Medicine, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chao-Long Chen
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Hsin-You Ou
- Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yu-Fan Cheng
- Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
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24
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Ward JW, Wanlapakorn N, Poovorawan Y, Shouval D. Hepatitis B Vaccines. PLOTKIN'S VACCINES 2023:389-432.e21. [DOI: 10.1016/b978-0-323-79058-1.00027-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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25
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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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26
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Jonas E, Bernon M, Robertson B, Kassianides C, Keli E, Asare KO, Alatise IO, Okello M, Blondel NO, Mulehane KO, Abubeker ZA, Nogoud AA, Nashidengo PR, Chihaka O, Tzeuton C, Dusheiko G, Sonderup M, Spearman CW. Treatment of hepatocellular carcinoma in sub-Saharan Africa: challenges and solutions. Lancet Gastroenterol Hepatol 2022; 7:1049-1060. [PMID: 35810767 DOI: 10.1016/s2468-1253(22)00042-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2021] [Revised: 01/30/2022] [Accepted: 02/02/2022] [Indexed: 06/15/2023]
Abstract
Most patients who develop hepatocellular carcinoma reside in resource-poor countries, a category that includes most countries in sub-Saharan Africa. Age-standardised incidence rates of hepatocellular carcinoma in western, central, eastern, and southern Africa is 6·53 per 100 000 inhabitants to 11·1 per 100 000 inhabitants. In high-income countries, around 40% of patients are diagnosed at an early stage, in which interventions with curative intent or palliative interventions are possible. By contrast, 95% of patients with hepatocellular carcinoma in sub-Saharan Africa present with advanced or terminal disease. In high-income countries, targets of 30-40% that have been set for intervention with curative intent are regularly met, with expected 5-year overall survival rates in the region of 70%. These outcomes are in sharp contrast with the very small proportion of patients in sub-Saharan Africa who are treated with curative intent. Primary prevention through the eradication and reduction of risk factors is still suboptimal because of logistical challenges. The challenges facing primary prevention, in combination with difficult-to-manage historic and emerging risk factors, such as ethanol overconsumption and metabolic dysfunction-associated liver disease, mandates secondary prevention for populations at risk through screening and surveillance. Although the increased treatment needs yielded by screening and surveillance in high-income countries are manageable by the incremental expansion of existing interventional resources, the lack of resources in sub-Saharan Africa will undermine the possible benefits of secondary prevention. An estimate of the projected effect of the introduction and expansion of screening and surveillance, resulting in stage migration and possibilities for active interventions for hepatocellular carcinoma, would facilitate optimal planning and development of resources.
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Affiliation(s)
- Eduard Jonas
- Department of Surgery, University of Cape Town, Cape Town, South Africa.
| | - Marc Bernon
- Department of Surgery, University of Cape Town, Cape Town, South Africa
| | - Barbara Robertson
- Division of Radiation Oncology, Department of Radiation Medicine, University of Cape Town, Cape Town, South Africa
| | - Chris Kassianides
- Department of Medicine, University of Cape Town, Cape Town, South Africa
| | - Elie Keli
- Department of General and Digestive Surgery, Hôpital Militaire d'Abidjan, Abidjan, Côte d'Ivoire
| | - Kwaku Offei Asare
- Department of Surgery, Korle Bu Teaching Hospital and the University of Ghana Medical School, Accra, Ghana
| | - Isaac Olusegun Alatise
- Department of Surgery, Obafemi Awolowo University, Obafemi Awolowo University Teaching Hospital Complex, Ile Ife, Nigeria
| | - Michael Okello
- Department of Surgery, Uganda Martyrs Hospital Lubaga, Kampala, Uganda
| | - Nana Oumarou Blondel
- Centre Hospitalier d'Essos and Department of Surgery, University of Yaoundé, Yaoundé, Cameroon
| | | | - Zeki Abdurahman Abubeker
- Department of Surgery, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | | | - Pueya Rashid Nashidengo
- Department of Surgery, Windhoek Central Hospital, University of Namibia School of Medicine, Windhoek, Namibia
| | - Onesai Chihaka
- Department of Surgery, University of Zimbabwe, Harare, Zimbabwe
| | - Christian Tzeuton
- Faculty of Medicine and Pharmaceutical Sciences of Douala, University of Douala, Douala, Cameroon
| | - Geoffrey Dusheiko
- Institute of Liver Studies, King's College Hospital, London, UK; University College London Medical School, London, UK
| | - Mark Sonderup
- Division of Hepatology, Department of Medicine, University of Cape Town, Cape Town, South Africa
| | - C Wendy Spearman
- Division of Hepatology, Department of Medicine, University of Cape Town, Cape Town, South Africa
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27
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Shukla A, Patkar S, Sundaram S, Shah SR, Ingle M, Gupta A, Gopan A, Kamat M, Mohanka R, Singh S, Walke S, Pandey V, Goel M. Clinical Profile, Patterns of Care & adherence to Guidelines in Patients with Hepatocellular Carcinoma: Prospective multi-center Study. J Clin Exp Hepatol 2022; 12:1463-1473. [PMID: 36340319 PMCID: PMC9630010 DOI: 10.1016/j.jceh.2022.05.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2021] [Accepted: 05/27/2022] [Indexed: 12/12/2022] Open
Abstract
Background and aims Increasing incidence of hepatocellular carcinoma (HCC) in India is a matter of concern and need for adequate profiling and streamlining management strategies cannot be over-emphasized. Methods This is a prospective multi-centric observational cohort study comprising of an oncology center, one university tertiary hospital with specialized hepatology service, one public hospital with gastroenterology service, and a private liver transplant center located within a 3-km radius. The demographic and clinical parameters were recorded on a prospectively maintained database. The clinical profile, demographics, characteristics of HCC and the allocated treatment were noted and compared among the four centers. Results In total, 672 patients were enrolled from June 2016 till January 2020. Abdominal pain (64.3%) and weight loss (47.3%) were the most common symptoms. Most common identified etiology was hepatitis B (39%). The cancer center received lesser patients with hepatitis C and those with advanced stage of HCC. The private transplant center reported the highest proportion of NASH, which was also significantly higher in those belonging to higher socioeconomic strata, and lowest proportion of alcoholic cirrhosis. Metastasis was seen in almost one-fifth (19%) cases at diagnosis. Portal vein thrombosis was evident in 40%. Adherence to treatment guidelines was seen in three-fourth cases (76%). Conclusions Hepatitis B is the most common underlying cause for HCC, whereas other causes like NASH are on the rise. Etiologic profile may vary with selective specialization of centers catering to patients with HCC. Adherence to guideline while allocating treatment was high among all centers with highest non-adherence in BCLC A.
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Key Words
- AASLD, American Association of Study of Liver Disease
- AFP, Alpha fetoprotein
- ALP, Alkaline phosphatase
- ALT, Alanine transaminase
- AST, Aspartate transaminase
- BCLC, Barcelona Clinic Liver Cancer staging
- BCS, Budd Chiari syndrome
- CT, Computed tomography
- EASL, European Association for Study of Liver
- GGT, Gamma glutamyl transpeptidase
- HBV, Hepatitis B virus
- HCC, Hepatocellular carcinoma
- HCV, Hepatitis C virus
- HKLC, Hong-Kong Liver Cancer staging
- HVPG, Hepatic venous pressure gradient
- INR, International normalized ratio
- MDT, Multidisciplinary team
- MRI, Magnetic resonance imaging
- NAFLD, Non-alcoholic fatty liver disease
- PHT, Portal hypertension
- PVTT, Portal venous tumor thrombosis
- clinical profile
- hepatocellular carcinoma
- milan criteria
- multicenter
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Affiliation(s)
- Akash Shukla
- Department of Gastroenterology, Seth G.S Medical College and King Edward Memorial Hospital, Mumbai, India
| | - Shraddha Patkar
- Department of Surgical Oncology, Tata Memorial Hospital, Mumbai, India
| | - Sridhar Sundaram
- Department of Gastroenterology, Seth G.S Medical College and King Edward Memorial Hospital, Mumbai, India
| | - Samir R. Shah
- Department of Hepatology, Institute of Liver Disease, Hepato-pancreatico-biliary Surgery and Transplant, Global Hospitals, Mumbai, India
| | - Meghraj Ingle
- Department of Gastroenterology, Lokmanya Tilak Municipal Medical College and General Hospital, Mumbai, India
| | - Amit Gupta
- Department of Surgical Oncology, Tata Memorial Hospital, Mumbai, India
| | - Amrit Gopan
- Department of Gastroenterology, Seth G.S Medical College and King Edward Memorial Hospital, Mumbai, India
| | - Mrunal Kamat
- Department of Hepatology, Institute of Liver Disease, Hepato-pancreatico-biliary Surgery and Transplant, Global Hospitals, Mumbai, India
| | - Ravi Mohanka
- Department of Hepatology, Institute of Liver Disease, Hepato-pancreatico-biliary Surgery and Transplant, Global Hospitals, Mumbai, India
| | - Sandeep Singh
- Department of Hepatology, Institute of Liver Disease, Hepato-pancreatico-biliary Surgery and Transplant, Global Hospitals, Mumbai, India
| | - Swapnil Walke
- Department of Gastroenterology, Lokmanya Tilak Municipal Medical College and General Hospital, Mumbai, India
| | - Vikas Pandey
- Department of Gastroenterology, Lokmanya Tilak Municipal Medical College and General Hospital, Mumbai, India
| | - Mahesh Goel
- Department of Surgical Oncology, Tata Memorial Hospital, Mumbai, India
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28
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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: 5] [Impact Index Per Article: 1.7] [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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29
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Mohamed EA, Giama NH, Abdalla AO, Shaleh HM, Oseini AM, Ali HA, Ahmed F, Taha W, Ahmed Mohammed H, Cvinar J, Waaeys IA, Ali H, Allotey LK, Ali AO, Mohamed SA, Harmsen WS, Ahmmad EM, Bajwa NA, Afgarshe MD, Shire AM, Balls-Berry JE, Roberts LR. High prevalence of chronic viral hepatitis B and C in Minnesota Somalis contributes to rising hepatocellular carcinoma incidence. World J Gastroenterol 2022; 28:5217-5229. [PMID: 36188718 PMCID: PMC9516675 DOI: 10.3748/wjg.v28.i35.5217] [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: 01/19/2022] [Revised: 03/28/2022] [Accepted: 08/17/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are known risk factors for liver disease, cirrhosis and hepatocellular carcinoma (HCC). There is substantial global variation in HBV and HCV prevalence resulting in variations in cirrhosis and HCC. We previously reported high prevalence of HBV and HCV infections in Somali immigrants seen at an academic medical center in Minnesota. AIM To determine the prevalence of chronic viral hepatitis in Somali immigrants in Minnesota through a community-based screening program. METHODS We conducted a prospective community-based participatory research study in the Somali community in Minnesota in partnership with community advisory boards, community clinics and local mosques between November 2010 and December 2015 (data was analyzed in 2020). Serum was tested for hepatitis B surface antigen, hepatitis B core antibody, hepatitis B surface antibody and anti-HCV antibody. RESULTS Of 779 participants, 15.4% tested positive for chronic HBV infection, 50.2% for prior exposure to HBV and 7.6% for chronic HCV infection. Calculated age-adjusted frequencies in males and females for chronic HBV were 12.5% and 11.6%; for prior exposure to HBV were 44.8% and 41.3%; and for chronic HCV were 6.7% and 5.7%, respectively. Seven participants developed incident HCC during follow up. CONCLUSION Chronic HBV and HCV are major risk factors for liver disease and HCC among Somali immigrants, with prevalence of both infections substantially higher than in the general United States population. Community-based screening is essential for identifying and providing health education and linkage to care for diagnosed patients.
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Affiliation(s)
- Essa A Mohamed
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
- Center for Clinical and Translational Science, Mayo Clinic, Rochester, MN 55905, United States
| | - Nasra H Giama
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
- School of Nursing, University of Minnesota, Minneapolis, MN 55455, United States
| | - Abubaker O Abdalla
- Division of Digestive Diseases, Emory School of Medicine, Atlanta, GA 30322, United States
| | - Hassan M Shaleh
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, United States
| | - Abdul M Oseini
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
| | - Hamdi A Ali
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
| | - Fowsiyo Ahmed
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
| | - Wesam Taha
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
- Department of Internal Medicine, NewYork-Presbyterian Queens, Flushing, NY 11355, United States
| | - Hager Ahmed Mohammed
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
- Department of Pediatrics, University of Nevada Las Vegas, Las Vegas, NV 89154, United States
| | - Jessica Cvinar
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
| | - Ibrahim A Waaeys
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, United States
| | - Hawa Ali
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
| | - Loretta K Allotey
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
| | - Abdiwahab O Ali
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, United States
| | - Safra A Mohamed
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, United States
| | - William S Harmsen
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, United States
| | - Eimad M Ahmmad
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
| | - Numra A Bajwa
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
| | - Mohamud D Afgarshe
- Department of Medicine, Gargar Urgent Care and Clinic, Minneapolis, MN 55406, United States
| | - Abdirashid M Shire
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
- Office of the Director, Shire Scientific, Minneapolis, MN 55405, United States
| | - Joyce E Balls-Berry
- Center for Clinical and Translational Science, Mayo Clinic, Rochester, MN 55905, United States
- Department of Neurology, Washington University School of Medicine in St Louis, St Louis, MO 63130, United States
- Knight Alzheimer Disease Research Center, Washington University School of Medicine, St Louis, MO 63130, United States
| | - Lewis R Roberts
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
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30
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Kim JY, Kim J, Lim YS, Gwak GY, Yeo I, Kim Y, Lee J, Shin D, Lee JH, Kim Y. Proteome Multimarker Panel for the Early Detection of Hepatocellular Carcinoma: Multicenter Derivation, Validation, and Comparison. ACS OMEGA 2022; 7:29934-29943. [PMID: 36061641 PMCID: PMC9434733 DOI: 10.1021/acsomega.2c02926] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 08/08/2022] [Indexed: 06/15/2023]
Abstract
Conventional methods for the surveillance of hepatocellular carcinoma (HCC) by imaging, with and without serum tumor markers, are suboptimal with regard to accuracy. We aimed to develop and validate a reliable serum biomarker panel for the early detection of HCC using a proteomic technique. This multicenter case-control study comprised 727 patients with HCC and patients with risk factors but no HCC. We developed a multiple reaction monitoring-mass spectrometry (MRM-MS) multimarker panel using 17 proteins from the sera of 398 patients. Area under the receiver operating characteristics curve (AUROC) values of this MRM-MS panel with and without α-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) were compared. The combination and standalone MRM-MS panels had higher AUROC values than AFP in the training (0.940 and 0.929 vs 0.775, both P < 0.05), test (0.894 and 0.893 vs 0.593, both P < 0.05), and confirmation sets (0.961 and 0.937 vs 0.806, both P < 0.05) in detecting small single HCC. The combination and standalone MRM-MS panels had significantly higher AUROC values than the GALAD score (0.945 and 0.931 vs 0.829, both P < 0.05). Our proteome 17-protein multimarker panel distinguished HCC patients from high-risk controls and had high accuracy in the early detection of HCC.
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Affiliation(s)
- Ju Yeon Kim
- Department
of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
| | - Jaenyeon Kim
- Interdisciplinary
Program of Bioengineering, Graduate School,
Seoul National University, Seoul 08826, Republic of Korea
| | - Young-Suk Lim
- Department
of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul 44610, Republic of Korea
| | - Geum-Youn Gwak
- Department
of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic
of Korea
| | - Injoon Yeo
- Interdisciplinary
Program of Bioengineering, Graduate School,
Seoul National University, Seoul 08826, Republic of Korea
| | - Yoseop Kim
- Interdisciplinary
Program of Bioengineering, Graduate School,
Seoul National University, Seoul 08826, Republic of Korea
| | - Jihyeon Lee
- Department
of Biomedical Sciences, Seoul National University
College of Medicine, Seoul 03080, Republic of Korea
| | - Dongyoon Shin
- Department
of Biomedical Sciences, Seoul National University
College of Medicine, Seoul 03080, Republic of Korea
| | - Jeong-Hoon Lee
- Department
of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
| | - Youngsoo Kim
- Interdisciplinary
Program of Bioengineering, Graduate School,
Seoul National University, Seoul 08826, Republic of Korea
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31
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Qian X, Liu Y, Wu F, Zhang S, Gong J, Nan Y, Hu B, Chen J, Zhao J, Chen X, Pan W, Dang S, Lu F. The Performance of Serum Alpha-Fetoprotein for Detecting Early-Stage Hepatocellular Carcinoma Is Influenced by Antiviral Therapy and Serum Aspartate Aminotransferase: A Study in a Large Cohort of Hepatitis B Virus-Infected Patients. Viruses 2022; 14:1669. [PMID: 36016291 PMCID: PMC9416230 DOI: 10.3390/v14081669] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Revised: 06/25/2022] [Accepted: 07/14/2022] [Indexed: 11/17/2022] Open
Abstract
Background and aims: Factors associated with abnormally elevated alpha-fetoprotein (AFP) in hepatitis B virus (HBV)-infected patients remain to be studied. We aimed to identify factors associated with elevated serum AFP in patients with non-hepatocellular carcinoma (HCC) and early-stage HCC and their influences on the performance of AFP for detecting early-stage HCC. Methods: This multicenter, retrospective study was conducted in 4401 patients with chronic HBV infection, including 3680 patients with non-HCC and 721 patients with early-stage HCC. Factors associated with elevated AFP were analyzed. Diagnostic performance of AFP for early-stage HCC were compared among groups through area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Results: When analyzed by multivariate logistic regression, antiviral therapy was negatively associated with elevated AFP, while hepatitis B e antigen (HBeAg) and aspartate aminotransferase (AST) > 1× upper limit of normal (ULN) were positively associated with elevated AFP both in patients with non-HCC and early-stage HCC (all p < 0.05). The AUCs of AFP for detecting early-stage HCC in patients with antiviral therapy, HBV DNA (−), alanine aminotransferase (ALT) ≤ 1× ULN, and AST ≤ 1× ULN were significantly higher compared to those in non-antiviral therapy, HBV DNA (+), ALT > 1× ULN, and AST > 1× ULN groups, respectively. When categorizing patients into AST ≤ 1× ULN and > 1× ULN, AFP achieved the highest AUCs in patients with AST ≤ 1× ULN regardless of antiviral treatment (AUCs = 0.813 and 0.806, respectively). Furthermore, there were considerable differences in the cut-off values of AFP in detecting early-stage HCC in different subgroups when applying similar sensitivity and specificity. Conclusions: Antiviral therapy and serum AST might be used to help judge and select the specific cut-off values of serum AFP for HCC surveillance in different at-risk populations.
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Affiliation(s)
- Xiangjun Qian
- Department of Microbiology, Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; (X.Q.); (Y.L.); (X.C.)
- Department of Pancreatic Hepatobiliary Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510655, China
| | - Yanna Liu
- Department of Microbiology, Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; (X.Q.); (Y.L.); (X.C.)
| | - Fengping Wu
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China;
| | - Siyu Zhang
- Department of Traditional and Western Medical Hepatology, The Third Hospital of Hebei Medical University, Shijiazhuang 050051, China; (S.Z.); (Y.N.)
| | - Jiao Gong
- Department of Laboratory Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China; (J.G.); (B.H.)
| | - Yuemin Nan
- Department of Traditional and Western Medical Hepatology, The Third Hospital of Hebei Medical University, Shijiazhuang 050051, China; (S.Z.); (Y.N.)
| | - Bo Hu
- Department of Laboratory Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China; (J.G.); (B.H.)
| | - Junhui Chen
- Intervention and Cell Therapy Center, Peking University Shenzhen Hospital, Shenzhen 518035, China;
| | - Jingmin Zhao
- Department of Pathology and Hepatology, The 5th Medical Centre, Chinese PLA General Hospital, Beijing 100039, China;
| | - Xiangmei Chen
- Department of Microbiology, Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; (X.Q.); (Y.L.); (X.C.)
| | - Weidong Pan
- Department of Pancreatic Hepatobiliary Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510655, China
| | - Shuangsuo Dang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China;
| | - Fengmin Lu
- Department of Microbiology, Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; (X.Q.); (Y.L.); (X.C.)
- Precision Medicine Center, Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450001, China
- Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Peking University Hepatology Institute, Peking University People’s Hospital, Beijing 100044, China
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Esteban JPG, Asgharpour A. Evaluation of liver transplant candidates with non-alcoholic steatohepatitis. Transl Gastroenterol Hepatol 2022; 7:24. [PMID: 35892057 PMCID: PMC9257540 DOI: 10.21037/tgh.2020.03.04] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Accepted: 02/03/2020] [Indexed: 11/07/2023] Open
Abstract
Non-alcoholic steatohepatitis (NASH) is anticipated to become the leading indication for liver transplantation (LT) in the United States in the near future. LT is indicated in patients with NASH-related cirrhosis who have medically refractory hepatic decompensation, synthetic dysfunction, and hepatocellular carcinoma (HCC) meeting certain criteria. The objective of LT evaluation is to determine which patient will derive the most benefit from LT with the least risk, thus maximizing the societal benefits of a limited resource. LT evaluation is a multidisciplinary undertaking involving several specialists, assessment tools, and diagnostic testing. Although the steps involved in LT evaluation are relatively similar across different liver diseases, patients with NASH-related cirrhosis have unique demographic and clinical features that affect transplant outcomes and influence their LT evaluation. LT candidates with NASH should be assessed for metabolic syndrome and obesity, malnutrition and sarcopenia, frailty, and cardiovascular disease. Interventions that treat cardiometabolic co-morbidities and improve patients' nutrition and functionality should be considered in order to improve patient outcomes in the waitlist and after LT.
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Affiliation(s)
- James Philip G Esteban
- Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, WI, USA
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Amon Asgharpour
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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33
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Huang Y, Luo W, Chen S, Su H, Zhu W, Wei Y, Qiu Y, Long Y, Shi Y, Wei J. Association of a Novel DOCK2 Mutation-Related Gene Signature With Immune in Hepatocellular Carcinoma. Front Genet 2022; 13:872224. [PMID: 35620462 PMCID: PMC9127407 DOI: 10.3389/fgene.2022.872224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Accepted: 04/08/2022] [Indexed: 11/30/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality worldwide. Many studies have shown that dedicator of cytokinesis 2 (DOCK2) has a crucial role as a prognostic factor in various cancers. However, the potentiality of DOCK2 in the diagnosis of HCC has not been fully elucidated. In this work, we aimed to investigate the prognostic role of DOCK2 mutation in HCC. The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) cohorts were utilized to identify the mutation frequency of DOCK2. Then, univariate Cox proportional hazard regression analysis, random forest (RF), and multivariate Cox regression analysis were performed to develop the risk score that was significantly related to DOCK2 mutation. Moreover, Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA), and immune correlation analysis were conducted for an in-depth study of the biological process of DOCK2 mutation involved in HCC. The results revealed that the mutation frequency of DOCK2 was relatively higher than that in non-cancer control subjects, and patients with DOCK2 mutations had a low survival rate and a poor prognosis compared with the DOCK2-wild group. In addition, the secretin receptor (SCTR), tetratricopeptide repeat, ankyrin repeat and coiled-coil domain-containing 1 (TANC1), Alkb homolog 7 (ALKBH7), FRAS1-related extracellular matrix 2 (FREM2), and G protein subunit gamma 4 (GNG4) were found to be the most relevant prognostic genes of DOCK2 mutation, and the risk score based on the five genes played an excellent role in predicting the status of survival, tumor mutation burden (TMB), and microsatellite instability (MSI) in DOCK2 mutant patients. In addition, DOCK2 mutation and the risk score were closely related to immune responses. In conclusion, the present study identifies a novel prognostic signature in light of DOCK2 mutation-related genes that shows great prognostic value in HCC patients; and this gene mutation might promote tumor progression by influencing immune responses. These data may provide valuable insights for future investigations into personalized forecasting methods and also shed light on stratified precision oncology treatment.
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Affiliation(s)
- Yushen Huang
- Pharmaceutical College, Guangxi Medical University, Nanning, China
| | - Wen Luo
- Department of Gastrointestinal Surgery, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, China
| | - Siyun Chen
- Pharmaceutical College, Guangxi Medical University, Nanning, China
| | - Hongmei Su
- Pharmaceutical College, Guangxi Medical University, Nanning, China
| | - Wuchang Zhu
- Pharmaceutical College, Guangxi Medical University, Nanning, China
| | - Yuanyuan Wei
- Pharmaceutical College, Guangxi Medical University, Nanning, China
| | - Yue Qiu
- Pharmaceutical College, Guangxi Medical University, Nanning, China
| | - Yan Long
- Pharmaceutical College, Guangxi Medical University, Nanning, China
| | - Yanxia Shi
- Pharmaceutical College, Guangxi Medical University, Nanning, China
| | - Jinbin Wei
- Pharmaceutical College, Guangxi Medical University, Nanning, China
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34
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Reappraisal of the roles of alpha-fetoprotein in hepatocellular carcinoma surveillance using large-scale nationwide database and hospital-based information. J Formos Med Assoc 2022; 121:2085-2092. [PMID: 35450743 DOI: 10.1016/j.jfma.2022.04.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2021] [Revised: 03/22/2022] [Accepted: 04/05/2022] [Indexed: 11/24/2022]
Abstract
BACKGROUND/PURPOSE Controversies over the use of alpha-fetoprotein (AFP) for detection of hepatocellular carcinoma (HCC) existed from guidelines. Using large-scale database and hospital-based information, we aimed to reappraise the role of AFP in HCC surveillance, including proportion of AFP elevation by stage of HCC, additional benefit of AFP in combination of ultrasonography (US) in the detection of early HCC, and survival in early HCC with high AFP levels. METHODS This retrospective study enrolled 43,437 patients from database of the Taiwan Cancer Registry (TCR) and 4250 patients from Kaohsiung Chang Gung Memorial Hospital (KCGMH) between January 2011 and December 2017. RESULTS The HCC cases in KCGMH accounted for 9.8% of the total cases in the TCR. Among both nationwide database and hospital-based information, the proportion of early HCC patients with an AFP level of ≥20 ng/mL was approximately 40%. In KCGMH, the proportion of patients with an AFP level of ≥20 ng/mL and a virus-related (hepatitis B and C) etiology was around 41.7%; furthermore, among patients with early HCC, those with an AFP level of ≥20 ng/mL had 4.7 years of median survival and 48.3% of the 5-year overall survival rate. By hospital electronic medical records review of early HCC cohort in KCGMH, approximately 10.9% of patients with AFP levels ≥20 ng/mL had US-undetectable early HCC. CONCLUSION This study suggested that AFP in combination with US would add an additional benefit as being a prompted role for detection of early HCC in patients with US-undetectable HCC.
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35
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Shiha G, Mikhail NNH, Soliman R, Hassan A, Eslam M. Predictive performance and clinical utility of HCC risk scores in chronic hepatitis C: a comparative study. Hepatol Int 2022; 16:159-170. [PMID: 35034266 DOI: 10.1007/s12072-021-10284-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Accepted: 12/06/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM Many HCC risk prediction scores were developed to guide HCC risk stratification and identify CHC patients who either need intensified surveillance or may not require screening. There is a need to compare different scores and their predictive performance in clinical practice. We aim to compare the newest HCC risk scores evaluating their discriminative ability, and clinical utility in a large cohort of CHC patients. PATIENTS AND METHODS The performance of the scores was evaluated in 3075 CHC patients who achieved SVR following DAAs using Log rank, Harrell's c statistic, also tested for HCC-risk stratification and negative predictive values. RESULTS HCC developed in 212 patients within 5 years follow-up. Twelve HCC risk scores were identified and displayed significant Log rank (p ≤ 0.05) except Alonso-Lopez TE-HCC, and Chun scores (p = 0.374, p = 0.053, respectively). Analysis of the remaining ten scores revealed that ADRES, GES pre-post treatment, GES algorithm and Watanabe (post-treatment) scores including dynamics of AFP, were clinically applicable and demonstrated good statistical performance; Log rank analysis < 0.001, Harrell's C statistic (0.66-0.83) and high negative predictive values (94.38-97.65%). In these three scores, the 5 years cumulative IR in low risk groups be very low (0.54-1.6), so screening could be avoided safely in these patients. CONCLUSION ADRES, GES (pre- and post-treatment), GES algorithm and Watanabe (post-treatment) scores seem to offer acceptable HCC-risk predictability and clinical utility in CHC patients. The dynamics of AFP as a component of these scores may explain their high performance when compared to other scores.
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Affiliation(s)
- Gamal Shiha
- Egyptian Liver Research Institute and Hospital (ELRIAH), Sherbin, Mansoura, Egypt.
- Hepatology and Gastroenterology Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
| | - Nabiel N H Mikhail
- Egyptian Liver Research Institute and Hospital (ELRIAH), Sherbin, Mansoura, Egypt
- Biostatistics and Cancer Epidemiology Department, South Egypt Cancer Institute, Assiut University, Assiut, Egypt
| | - Reham Soliman
- Egyptian Liver Research Institute and Hospital (ELRIAH), Sherbin, Mansoura, Egypt
- Tropical Medicine Department, Faculty of Medicine, Port Said University, Port Said, Egypt
| | - Ayman Hassan
- Egyptian Liver Research Institute and Hospital (ELRIAH), Sherbin, Mansoura, Egypt
| | - Mohammed Eslam
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia
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36
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Fukushima T, Morimoto M, Ueno M, Kubota K, Uojima H, Hidaka H, Chuma M, Numata K, Tsuruya K, Hirose S, Kagawa T, Hattori N, Watanabe T, Matsunaga K, Yamamoto K, Tanaka K, Maeda S. Comparative study between sorafenib and lenvatinib as the first-line therapy in the sequential treatment of unresectable hepatocellular carcinoma in a real-world setting. JGH Open 2022; 6:29-35. [PMID: 35071785 PMCID: PMC8762625 DOI: 10.1002/jgh3.12691] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 10/20/2021] [Accepted: 11/28/2021] [Indexed: 11/28/2022]
Abstract
AIMS There is a paucity of comparative data on the use of sorafenib and lenvatinib for unresectable hepatocellular carcinoma. We assessed the real-world treatment outcomes between using sorafenib and lenvatinib for unresectable hepatocellular carcinoma in the multiple molecular-targeted therapy era. METHODS AND RESULTS We enrolled 386 patients treated with sorafenib or lenvatinib as the first-line therapy for unresectable hepatocellular carcinoma at multiple centers. Propensity score matching was performed to adjust for differences in baseline and tumor characteristics between the two groups. Propensity score matching identified 110 patients in each treatment group. The median overall survival was similar between lenvatinib and sorafenib (14.8 and 13.0 months, respectively; P = 0.352). The median progression-free survival was longer with lenvatinib than with sorafenib (7.6 and 3.9 months, respectively; P < 0.001). The overall response rate (P < 0.001) and disease control rate (P = 0.015), as defined by the modified Response Evaluation Criteria in Solid Tumors, were significantly better with lenvatinib than with sorafenib. The median overall survival was longer in patients who received subsequent treatment than in those who did not in the sorafenib group (23.1 and 5.7 months, respectively; P < 0.001), whereas the median overall survival with or without subsequent treatment did not differ significantly in the lenvatinib group (17.8 and 14.7 months, respectively; P = 0.439). CONCLUSION Overall survival with sorafenib and lenvatinib was not significantly different. However, patients who received subsequent treatments had longer overall survival than those who received only first-line treatment with sorafenib, whereas lenvatinib did not show this effect.
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Affiliation(s)
- Taito Fukushima
- Hepatobiliary and Pancreatic OncologyKanagawa Cancer CenterYokohamaKanagawaJapan
- Department of GastroenterologyYokohama City University Graduate School of MedicineYokohamaKanagawaJapan
| | - Manabu Morimoto
- Hepatobiliary and Pancreatic OncologyKanagawa Cancer CenterYokohamaKanagawaJapan
| | - Makoto Ueno
- Hepatobiliary and Pancreatic OncologyKanagawa Cancer CenterYokohamaKanagawaJapan
| | - Kousuke Kubota
- Department of Gastroenterology, Internal MedicineKitasato University School of MedicineSagamiharaKanagawaJapan
| | - Haruki Uojima
- Department of Gastroenterology, Internal MedicineKitasato University School of MedicineSagamiharaKanagawaJapan
| | - Hisashi Hidaka
- Department of Gastroenterology, Internal MedicineKitasato University School of MedicineSagamiharaKanagawaJapan
| | - Makoto Chuma
- Gastroenterological CenterYokohama City University Medical CenterYokohamaKanagawaJapan
| | - Kazushi Numata
- Gastroenterological CenterYokohama City University Medical CenterYokohamaKanagawaJapan
| | - Kota Tsuruya
- Division of Gastroenterology and Hepatology, Department of Internal MedicineTokai University School of MedicineIseharaKanagawaJapan
| | - Shunji Hirose
- Division of Gastroenterology and Hepatology, Department of Internal MedicineTokai University School of MedicineIseharaKanagawaJapan
| | - Tatehiro Kagawa
- Division of Gastroenterology and Hepatology, Department of Internal MedicineTokai University School of MedicineIseharaKanagawaJapan
| | - Nobuhiro Hattori
- Division of Gastroenterology and Hepatology, Department of Internal MedicineSt. Marianna University School of MedicineKawasakiKanagawaJapan
| | - Tsunamasa Watanabe
- Division of Gastroenterology and Hepatology, Department of Internal MedicineSt. Marianna University School of MedicineKawasakiKanagawaJapan
| | - Kotaro Matsunaga
- Division of Gastroenterology and HepatologyKawasaki Municipal Tama HospitalKawasakiKanagawaJapan
| | - Kouji Yamamoto
- Department of Biostatistics, School of MedicineYokohama City UniversityYokohamaKanagawaJapan
| | - Katsuaki Tanaka
- Gastroenterology DivisionHadano Red Cross HospitalHadanoKanagawaJapan
| | - Shin Maeda
- Department of GastroenterologyYokohama City University Graduate School of MedicineYokohamaKanagawaJapan
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Park J, Lee JM, Kim TH, Yoon JH. Imaging Diagnosis of HCC: Future directions with special emphasis on hepatobiliary MRI and contrast-enhanced ultrasound. Clin Mol Hepatol 2021; 28:362-379. [PMID: 34955003 PMCID: PMC9293611 DOI: 10.3350/cmh.2021.0361] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Accepted: 12/21/2021] [Indexed: 11/16/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a unique cancer entity that can be noninvasively diagnosed using imaging modalities without pathologic confirmation. In 2018, several major guidelines for HCC were updated to include hepatobiliary contrast agent magnetic resonance imaging (HBA-MRI) and contrast-enhanced ultrasound (CEUS) as major imaging modalities for HCC diagnosis. HBA-MRI enables the achievement of high sensitivity in HCC detection using the hepatobiliary phase (HBP). CEUS is another imaging modality with real-time imaging capability, and it is reported to be useful as a second-line modality to increase sensitivity without losing specificity for HCC diagnosis. However, until now, there is an unsolved discrepancy among guidelines on whether to accept “HBP hypointensity” as a definite diagnostic criterion for HCC or include CEUS in the diagnostic algorithm for HCC diagnosis. Furthermore, there is variability in terminology and inconsistencies in the definition of imaging findings among guidelines; therefore, there is an unmet need for the development of a standardized lexicon. In this article, we review the performance and limitations of HBA-MRI and CEUS after guideline updates in 2018 and briefly introduce some future aspects of imaging-based HCC diagnosis.
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Affiliation(s)
- Junghoan Park
- Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea
| | - Jeong Min Lee
- Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul, Republic of Korea.,Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea
| | - Tae-Hyung Kim
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Jeong Hee Yoon
- Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul, Republic of Korea
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38
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Qiao EM, Lynch JA, Lee KM, Kotha NV, Nalawade V, Voora RS, Qian AS, Nelson TJ, Yamoah K, Garraway IP, Stewart TF, Parsons JK, Rose BS. Evaluating Prostate-Specific Antigen Screening for Young African American Men With Cancer. J Natl Cancer Inst 2021; 114:592-599. [PMID: 34893859 PMCID: PMC9002290 DOI: 10.1093/jnci/djab221] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 08/02/2021] [Accepted: 11/30/2021] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Despite higher risks associated with prostate cancer, young African American men are poorly represented in prostate-specific antigen (PSA) trials, which limits proper evidence-based guidance. We evaluated the impact of PSA screening, alongside primary care provider utilization, on prostate cancer outcomes for these patients. METHODS We identified African American men aged 40-55 years, diagnosed with prostate cancer between 2004 and 2017 within the Veterans Health Administration. Inverse probability of treatment-weighted propensity scores were used in multivariable models to assess PSA screening on PSA levels higher than 20, Gleason score of 8 or higher, and metastatic disease at diagnosis. Lead-time adjusted Fine-Gray regression evaluated PSA screening on prostate cancer-specific mortality (PCSM), with noncancer death as competing events. All statistical tests were 2-sided. RESULTS The cohort included 4726 patients. Mean age was 51.8 years, with 84-month median follow-up. There were 1057 (22.4%) with no PSA screening prior to diagnosis. Compared with no screening, PSA screening was associated with statistically significantly reduced odds of PSA levels higher than 20 (odds ratio [OR] = 0.56, 95% confidence interval [CI] = 0.49 to 0.63; P < .001), Gleason score of 8 or higher (OR = 0.78, 95% CI = 0.69 to 0.88; P < .001), and metastatic disease at diagnosis (OR = 0.50, 95% CI = 0.39 to 0.64; P < .001), and decreased PCSM (subdistribution hazard ratio = 0.52, 95% CI = 0.36 to 0.76; P < .001). Primary care provider visits displayed similar effects. CONCLUSIONS Among young African American men diagnosed with prostate cancer, PSA screening was associated with statistically significantly lower risk of PSA levels higher than 20, Gleason score of 8 or higher, and metastatic disease at diagnosis and statistically significantly reduced risk of PCSM. However, the retrospective design limits precise estimation of screening effects. Prospective studies are needed to validate these findings.
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Affiliation(s)
- Edmund M Qiao
- Veterans Affairs San Diego Health Care System, La Jolla, San Diego, CA, USA,Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, San Diego, CA, USA
| | - Julie A Lynch
- Veterans Affairs Salt Lake City Health Care System, Salt Lake City, UT, USA
| | - Kyung M Lee
- Veterans Affairs Salt Lake City Health Care System, Salt Lake City, UT, USA
| | - Nikhil V Kotha
- Veterans Affairs San Diego Health Care System, La Jolla, San Diego, CA, USA,Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, San Diego, CA, USA
| | - Vinit Nalawade
- Veterans Affairs San Diego Health Care System, La Jolla, San Diego, CA, USA,Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, San Diego, CA, USA
| | - Rohith S Voora
- Veterans Affairs San Diego Health Care System, La Jolla, San Diego, CA, USA,Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, San Diego, CA, USA
| | - Alexander S Qian
- Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, San Diego, CA, USA
| | - Tyler J Nelson
- Veterans Affairs San Diego Health Care System, La Jolla, San Diego, CA, USA,Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, San Diego, CA, USA
| | - Kosj Yamoah
- Department of Radiation Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA
| | - Isla P Garraway
- Department of Urology, University of California Los Angeles, Los Angeles, CA, USA
| | - Tyler F Stewart
- Division of Hematology-Oncology, Department of Internal Medicine, University of California San Diego, La Jolla, CA, USA
| | - J Kellogg Parsons
- Department of Urology, University of California San Diego, La Jolla, San Diego, CA, USA
| | - Brent S Rose
- Correspondence to: Brent S. Rose, MD, Department of Radiation Medicine and Applied Sciences, University of California, 3960 Health Sciences Drive, La Jolla, San Diego, CA 92093-0865, USA (e-mail: )
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39
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Aydin Y, Koksal AR, Thevenot P, Chava S, Heidari Z, Lin D, Sandow T, Moroz K, Parsi MA, Scott J, Cohen A, Dash S. Experimental Validation of Novel Glypican 3 Exosomes for the Detection of Hepatocellular Carcinoma in Liver Cirrhosis. J Hepatocell Carcinoma 2021; 8:1579-1596. [PMID: 34917553 PMCID: PMC8671108 DOI: 10.2147/jhc.s327339] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Accepted: 11/18/2021] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND AND AIMS Hepatocellular carcinoma (HCC) developing in the context of preexisting cirrhosis is characterized by impaired autophagy that results in increased exosome release. This study was conducted to determine whether circulating exosomes expressing glypican 3 (GPC3) could be utilized as a biomarker for HCC detection and treatment response in patients with cirrhosis. METHODS Immunohistochemistry was performed to assess p62 and GPC3 expression in the lesion and adjacent tissue from cirrhosis with HCC. GPC3-enriched exosomes were captured by an enzyme-linked immunosorbent assay (ELISA). The diagnostic specificity of serum exosome-derived GPC3 (eGPC3) was determined using samples obtained from malignancy-free controls, malignancy-free cirrhotics, cirrhotics with confirmed HCC, and patients with a non-HCC malignancy. The performance of eGPC3 was validated using serum samples of HCC patients received chemotherapy. RESULTS We found that the expression of p62 and GPC3 was significantly increased in HCC tissues compared to adjacent cirrhotic liver. Impaired autophagy and exosome shedding were confirmed in HCC cell lines. Mass spectroscopic analysis revealed that GPC3 was enriched in exosomes isolated from HCC cell lines. An affinity ELISA assay was developed that specifically captures GPC3 positive exosomes in the serum. Total exosome concentration and eGPC3 were significantly elevated in cirrhotic patients with HCC as compared to the reference control groups. Furthermore, decreases in post-treatment exosome concentration and eGPC3 levels were more closely correlated with response to locoregional chemotherapy compared to change in serum AFP in HCC patients awaiting liver transplantation. CONCLUSION We developed an affinity exosome capture assay to detect GPC3 enriched exosomes. Our preliminary assessment shows that GPC3 positive exosomes can be used for HCC detection and prediction of treatment outcomes.
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Affiliation(s)
- Yucel Aydin
- Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, New Orleans, LA, USA
| | - Ali Riza Koksal
- Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, New Orleans, LA, USA
- Department of Gastroenterology and Hepatology, Tulane University Health Sciences Center, New Orleans, LA, USA
| | - Paul Thevenot
- Institute of Translational Research, Ochsner Health, New Orleans, LA, USA
| | - Srinivas Chava
- Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, New Orleans, LA, USA
| | - Zahra Heidari
- Chemical and Biomedical Engineering, Tulane University, New Orleans, LA, USA
| | - Dong Lin
- Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, New Orleans, LA, USA
| | - Tyler Sandow
- Department of Radiology, Institute of Translational Research, Ochsner Health, New Orleans, LA, USA
| | - Krzysztof Moroz
- Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, New Orleans, LA, USA
| | - Mansour A Parsi
- Department of Gastroenterology and Hepatology, Tulane University Health Sciences Center, New Orleans, LA, USA
| | - John Scott
- Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, New Orleans, LA, USA
| | - Ari Cohen
- Institute of Translational Research, Ochsner Health, New Orleans, LA, USA
- Multi-Organ Transplant Institute, Ochsner Health, New Orleans, LA, USA
| | - Srikanta Dash
- Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, New Orleans, LA, USA
- Southeast Louisiana Veterans Health Care System, New Orleans, LA, USA
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Crouchet E, Schuster C, Baumert TF. Liver cell circuits and therapeutic discovery for advanced liver disease and cancer. C R Biol 2021; 344:233-248. [PMID: 35786628 PMCID: PMC7613418 DOI: 10.5802/crbiol.64] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 10/11/2021] [Indexed: 11/24/2022]
Abstract
Hepatocellular carcinoma (HCC) is a major global health challenge with rising incidence. Despite the previous approval of several novel therapeutic approaches, HCC remains the second common cause of cancer-related death worldwide. The vast majority of HCCs arises in the context of chronic fibrotic liver diseases caused by viral or metabolic etiologies. In patients with advanced liver disease the risk of HCC persists even after viral cure or control of infection. Moreover, given the change in the lifestyle and increase of obesity and metabolic disorders, HCC incidence is predicted to drastically augment in the next decade. Early detection, improvement of the screening method in patient at-risk and development of chemopreventive strategies are therefore urgently needed to reduce HCC risk. This review summarizes the major challenges in the identification of patient at risk for HCC and the emergent strategies for HCC prevention to improve patients’ outcome.
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Hernandez-Meza G, Vietti Violi N, Said D, Novogrodsky E, Villavisanis D, Maron SZ, Frere J, Schiano TD, Friedman S, Boffetta P, Branch A, Taouli B. MRI is the most commonly used imaging modality for HCC screening at a tertiary care transplant center. Abdom Radiol (NY) 2021; 46:5142-5151. [PMID: 34283266 DOI: 10.1007/s00261-021-03212-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Revised: 05/25/2021] [Accepted: 07/08/2021] [Indexed: 12/18/2022]
Abstract
PURPOSE In this study, we describe the patterns of hepatocellular carcinoma (HCC) screening with imaging and factors associated with imaging modality selection in a tertiary care transplant center. METHODS This was a retrospective study where all adult patients with cirrhosis and/or chronic hepatitis B virus infection referred for HCC screening with ultrasound (US), CT or MRI were identified during 2017. The association between imaging methods, demographic/clinical data were analyzed by uni- and multivariate analysis. RESULTS A total of 1437 patients were included (median age 61y, 59% male, median BMI 27.5 kg/m2, median AFP 3.4 ng/mL, 37% with HCV and 87% with cirrhosis). Index screening imaging method utilization included MRI (51%), US (33%) and CT (16%). Use of US as the index imaging modality for screening was significantly associated with race/ethnicity [Odds Ratio (OR) 1.71-2.01, all p < 0.05] in multivariate analysis. Presence of cirrhosis (OR 0.29, p < 0.001) and referral by a hepatologist (OR 0.23, p < 0.001) were associated with screening with MRI in the multivariate analysis; while gender, age, BMI, etiology and income at ZIP code of residence were not significantly associated with imaging modality selection. HCC was observed in 62 patients (prevalence 4.3%). Rate of HCC detection was significantly higher with MRI vs US (5.9% vs. 1.5%, p = 0.001). CONCLUSION MRI was the most frequently used modality (> 50%) for HCC screening in our tertiary care center, in contrast with the current practice guidelines. Race/ethnicity, cirrhosis and referral by a hepatologist were associated with the imaging method used for HCC screening.
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Affiliation(s)
- Gabriela Hernandez-Meza
- Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai (ISMMS), 1470 Madison Avenue, New York, NY, 10029, USA
- BioMedical Engineering and Imaging Institute, ISMMS, 1470 Madison Avenue, New York, NY, 10029, USA
| | - Naik Vietti Violi
- BioMedical Engineering and Imaging Institute, ISMMS, 1470 Madison Avenue, New York, NY, 10029, USA
- Department of Radiology, Lausanne University Hospital, Lausanne, Switzerland
| | - Daniela Said
- BioMedical Engineering and Imaging Institute, ISMMS, 1470 Madison Avenue, New York, NY, 10029, USA
- Department of Radiology, Universidad de los Andes, Santiago, Chile
| | - Eitan Novogrodsky
- Department of Radiology, Albert Einstein College of Medicine, New York, NY, USA
| | - Dillan Villavisanis
- Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai (ISMMS), 1470 Madison Avenue, New York, NY, 10029, USA
- BioMedical Engineering and Imaging Institute, ISMMS, 1470 Madison Avenue, New York, NY, 10029, USA
| | - Samuel Z Maron
- Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai (ISMMS), 1470 Madison Avenue, New York, NY, 10029, USA
- BioMedical Engineering and Imaging Institute, ISMMS, 1470 Madison Avenue, New York, NY, 10029, USA
| | - Justin Frere
- Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai (ISMMS), 1470 Madison Avenue, New York, NY, 10029, USA
- BioMedical Engineering and Imaging Institute, ISMMS, 1470 Madison Avenue, New York, NY, 10029, USA
| | - Thomas D Schiano
- Recanati/Miller Transplantation Institute, ISMMS, New York, NY, USA
| | | | - Paolo Boffetta
- Tisch Cancer Institute, ISMMS, New York, NY, USA
- Department of Family, Population & Preventive Medicine, Renaissance School of Medicine, Stony Brook, NY, USA
| | - Andrea Branch
- Division of Liver Diseases, ISMMS, New York, NY, USA
| | - Bachir Taouli
- Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai (ISMMS), 1470 Madison Avenue, New York, NY, 10029, USA.
- BioMedical Engineering and Imaging Institute, ISMMS, 1470 Madison Avenue, New York, NY, 10029, USA.
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Yeo YH, Hwang J, Jeong D, Dang N, Kam LY, Henry L, Park H, Cheung R, Nguyen MH. Surveillance of patients with cirrhosis remains suboptimal in the United States. J Hepatol 2021; 75:856-864. [PMID: 33965477 DOI: 10.1016/j.jhep.2021.04.042] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 04/10/2021] [Accepted: 04/26/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS Regular monitoring/surveillance for liver complications is crucial to reduce morbidity and mortality in patients with cirrhosis. Recommendations from professional societies are available but adherence is not well studied, especially outside of academic centers. We aimed to determine the frequencies and factors associated with laboratory monitoring, and hepatocellular carcinoma (HCC) and esophageal varices (EV) surveillance in patients with cirrhosis. METHODS We identified 82,427 patients with cirrhosis (43,280 compensated and 39,147 decompensated) from the Truven Health MarketScan Research Database®, 2007-2016. We calculated the proportion of patients with cirrhosis with various frequencies of procedures/testing: laboratory (complete blood count, comprehensive metabolic panel, and prothrombin time), HCC and EV surveillance. We also used multivariable logistic regression to determine factors associated with having procedures. RESULTS The proportions of patients undergoing HCC surveillance (8.78%), laboratory testing (29.72%) at least every 6-12 months, or EV surveillance (10.6%) at least every 1-2 years were suboptimal. The majority did not have HCC (45.4%) or EV (80.3%) surveillance during the entire study period. On multivariable regression, age 41-55 (vs. <41) years, preferred provider organization (vs. health maintenance organization) insurance plan, specialist care (vs. primary care and other specialties), diagnosis between 2013-2016 (vs. 2007-2009), decompensated (vs. compensated) cirrhosis, non-alcoholic fatty liver disease (vs. viral hepatitis), and higher Charlson comorbidity index were associated with significantly higher odds of undergoing procedures/testing every 6-12 months and EV surveillance every 1-2 years. CONCLUSIONS Despite modest improvements in more recent years, routine monitoring and surveillance for patients with cirrhosis is suboptimal. Further efforts including provider awareness, patient education, and system/incentive-based quality improvement measures are urgently needed. LAY SUMMARY Patients with cirrhosis should undergo health monitoring for liver complications to achieve early detection and treatment. In a large nationwide cohort of 82,427 patients with cirrhosis in the United States, we found a low rate of adherence (well less than half) to routine blood test monitoring and surveillance for liver cancer and esophageal varices (swollen blood vessels in the abdomen that could lead to fatal bleeding). Adherence has increased in the recent years, but much more improvement is needed.
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Affiliation(s)
- Yee Hui Yeo
- Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, United States; Division of General Internal Medicine, Cedars-Sinai Medical Center, Los Angeles, California, United States
| | - Jungyun Hwang
- Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, United States
| | - Donghak Jeong
- Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, United States
| | - Nolan Dang
- Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, United States
| | - Leslie Y Kam
- Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, United States
| | - Linda Henry
- Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, United States
| | - Haesuk Park
- Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, United States
| | - Ramsey Cheung
- Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, United States; Department of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, United States
| | - Mindie H Nguyen
- Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, United States; Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, California, United States; Stanford Cancer Institute, Stanford University Medical Center, Palo Alto, California, United States.
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Choi HH, Rodgers SK, Fetzer DT, Wasnik AP, Millet JD, Morgan TA, Dawkins A, Gabriel H, Kamaya A. Ultrasound Liver Imaging Reporting and Data System (US LI-RADS): An Overview with Technical and Practical Applications. Acad Radiol 2021; 28:1464-1476. [PMID: 32718745 DOI: 10.1016/j.acra.2020.06.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Revised: 06/01/2020] [Accepted: 06/01/2020] [Indexed: 12/12/2022]
Abstract
The Ultrasound Liver Imaging Reporting and Data System (US LI-RADS), introduced in 2017 by the American College of Radiology, standardizes the technique, interpretation, and reporting of screening and surveillance ultrasounds intended to detect hepatocellular carcinoma in high-risk patients. These include patients with cirrhosis of any cause as well as subsets of patients with chronic hepatitis B viral infection. The US LI-RADS scheme is composed of an ultrasound category and a visualization score: ultrasound categories define the exam as negative, subthreshold, or positive and direct next steps in management; visualization scores denote the expected sensitivity of the exam, based on adequacy of liver visualization with ultrasound. Since its introduction, multiple institutions across the United States have implemented US LI-RADS. This review includes a background of hepatocellular carcinoma and US LI-RADS, definition of screening/surveillance population, recommendations and tips for technique, interpretation, and reporting, and preliminary outcomes analysis.
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Affiliation(s)
- Hailey H Choi
- Department of Radiology and Biomedical Imaging, University of California San Francisco, 1001 Potrero Ave. Building 5, 1st floor, San Francisco, CA 94110.
| | - Shuchi K Rodgers
- Department of Radiology, Einstein Medical Center, Philadelphia, Pennsylvania
| | - David T Fetzer
- Department of Radiology, UT Southwestern Medical Center, Dallas Texas
| | - Ashish P Wasnik
- Department of Radiology, Michigan Medicine, University of Michigan, Arbor, Michigan
| | - John D Millet
- Department of Radiology, Michigan Medicine, University of Michigan, Arbor, Michigan
| | - Tara A Morgan
- Department of Radiology and Biomedical Imaging, University of California San Francisco, 1001 Potrero Ave. Building 5, 1st floor, San Francisco, CA 94110
| | - Adrian Dawkins
- Department of Radiology, University of Kentucky, Lexington, Kentucky
| | - Helena Gabriel
- Department of Radiology, Northwestern University, Chicago, Illinois
| | - Aya Kamaya
- Department of Radiology, Stanford University Medical Center, Stanford, California
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Qiao EM, Voora RS, Nalawade V, Kotha NV, Qian AS, Nelson TJ, Durkin M, Vitzthum LK, Murphy JD, Stewart TF, Rose BS. Evaluating the clinical trends and benefits of low-dose computed tomography in lung cancer patients. Cancer Med 2021; 10:7289-7297. [PMID: 34528761 PMCID: PMC8525167 DOI: 10.1002/cam4.4229] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 07/30/2021] [Accepted: 07/31/2021] [Indexed: 12/19/2022] Open
Abstract
Background Despite guideline recommendations, utilization of low‐dose computed tomography (LDCT) for lung cancer screening remains low. The driving factors behind these low rates and the real‐world effect of LDCT utilization on lung cancer outcomes remain limited. Methods We identified patients diagnosed with non‐small cell lung cancer (NSCLC) from 2015 to 2017 within the Veterans Health Administration. Multivariable logistic regression assessed the influence of LDCT screening on stage at diagnosis. Lead time correction using published LDCT lead times was performed. Cancer‐specific mortality (CSM) was evaluated using Fine–Gray regression with non‐cancer death as a competing risk. A lasso machine learning model identified important predictors for receiving LDCT screening. Results Among 4664 patients, mean age was 67.8 with 58‐month median follow‐up, 95% CI = [7–71], and 118 patients received ≥1 screening LDCT before NSCLC diagnosis. From 2015 to 2017, LDCT screening increased (0.1%–6.6%, mean = 1.3%). Compared with no screening, patients with ≥1 LDCT were more than twice as likely to present with stage I disease at diagnosis (odds ratio [OR] 2.16 [95% CI 1.46–3.20]) and less than half as likely to present with stage IV (OR 0.38 [CI 0.21–0.70]). Screened patients had lower risk of CSM even after adjusting for LDCT lead time (subdistribution hazard ratio 0.60 [CI 0.42–0.85]). The machine learning model achieved an area under curve of 0.87 and identified diagnosis year and region as the most important predictors for receiving LDCT. White, non‐Hispanic patients were more likely to receive LDCT screening, whereas minority, older, female, and unemployed patients were less likely. Conclusions Utilization of LDCT screening is increasing, although remains low. Consistent with randomized data, LDCT‐screened patients were diagnosed at earlier stages and had lower CSM. LDCT availability appeared to be the main predictor of utilization. Providing access to more patients, including those in diverse racial and socioeconomic groups, should be a priority.
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Affiliation(s)
- Edmund M Qiao
- Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California, USA.,Veterans Health Administration San Diego Health Care System, La Jolla, California, USA
| | - Rohith S Voora
- Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California, USA.,Veterans Health Administration San Diego Health Care System, La Jolla, California, USA
| | - Vinit Nalawade
- Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California, USA.,Veterans Health Administration San Diego Health Care System, La Jolla, California, USA
| | - Nikhil V Kotha
- Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California, USA.,Veterans Health Administration San Diego Health Care System, La Jolla, California, USA
| | - Alexander S Qian
- Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California, USA.,Veterans Health Administration San Diego Health Care System, La Jolla, California, USA
| | - Tyler J Nelson
- Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California, USA.,Veterans Health Administration San Diego Health Care System, La Jolla, California, USA
| | - Michael Durkin
- Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California, USA
| | - Lucas K Vitzthum
- Department of Radiation Oncology, Stanford University, Stanford, California, USA
| | - James D Murphy
- Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California, USA.,Veterans Health Administration San Diego Health Care System, La Jolla, California, USA
| | - Tyler F Stewart
- Division of Hematology-Oncology, Department of Internal Medicine, University of California San Diego, La Jolla, California, USA
| | - Brent S Rose
- Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California, USA.,Veterans Health Administration San Diego Health Care System, La Jolla, California, USA
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Huang DQ, Yeo YH, Nguyen MH. Letter to the Editor: Hepatocellular Carcinoma Surveillance in Cirrhosis Patients: Is the Real-World Situation Even Worse Than Reported? Hepatology 2021; 74:1714-1715. [PMID: 33617661 DOI: 10.1002/hep.31760] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Affiliation(s)
- Daniel Q Huang
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.,Division of Gastroenterology and Hepatology, National University Health System, Singapore
| | - Yee Hui Yeo
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA.,Division of General Internal Medicine, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA.,Department of Epidemiology and Population Health, Stanford University, Palo Alto, CA
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Role of Ultrasound for Chronic Liver Disease and Hepatocellular Carcinoma Surveillance. Magn Reson Imaging Clin N Am 2021; 29:279-290. [PMID: 34243917 DOI: 10.1016/j.mric.2021.05.005] [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: 11/23/2022]
Abstract
Ultrasound plays a vital role in the evaluation of patients with chronic liver disease and in hepatocellular carcinoma (HCC) surveillance in populations at risk for developing HCC. Semiannual ultrasound for HCC surveillance is universally recommended by all liver societies around the world. Advanced ultrasound techniques, such as elastography and contrast-enhanced ultrasound, offer additional benefits in imaging evaluation of chronic liver disease. Major benefits of ultrasound include its high safety profile and relatively low cost.
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Lin CW, Chen YS, Lo GH, Wu TC, Yeh JH, Yeh ML, Dai CY, Huang JF, Chuang WL, Roberts L, Jun DW, Toyoda H, Yasuda S, Nguyen MH, Yu ML. Resubclassification and clinical management for Barcelona Clinic Liver Cancer Stage C hepatocellular carcinoma. Hepatol Int 2021; 15:946-956. [PMID: 34008091 DOI: 10.1007/s12072-021-10169-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Accepted: 02/23/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Patients with Barcelona Clinic Liver Cancer Stage C (BCLC-C) hepatocellular carcinoma (HCC) can be markedly heterogeneous with varying prognosis. This study aims to establish a new subclassification system for BCLC-C HCC to better predict overall survival (OS) and to tailor therapy. METHODS We retrospectively studied 1856 BCLC-C HCC patients between 2006 and 2017 from E-Da Hospital, Taiwan (n = 622, training cohort), Kaohsiung Medical University Hospital, Taiwan (n = 774, Taiwan validation cohort), and Stanford University Medical Center and Mayo Clinic (United States), Hanyang University Hospital (South Korea), and Ogaki Municipal Hospital (Japan) to make up the international validation cohort (n = 460). RESULTS In the training cohort, significant factors associated with OS were largest tumor size ≥ 10 cm, extrahepatic spread, macrovascular invasion, and Child-Pugh class, which provided the basis, together with aged ≥ 75 years, for the substaging, through C0 to C4, of BCLC-C HCC patients. The median OS for substages C0, C1, C2, C3, and C4 were 43.8 months (95% confidence interval [CI] 32.2-53.7), 20.6 months (CI 14.1-25.9), 11.5 months (CI 8.02-14.1), 5.7 months (CI 4.02-5.98), and 3.2 months (CI 2.41-3.59), respectively, (p < 0.05). OS remained distinct among the proposed substages in the Taiwan validation cohort as well as the international validation cohort. The distinction between the substages persisted in subgroup analysis by substage combined with treatment modality. In substage C0-C3, patients receiving HCC curative therapy had a significantly better median OS than those receiving sorafenib or palliative therapy. CONCLUSION Our new substaging system provides more precise prognosis to better tailor therapy for BCLC-C HCC patients.
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Affiliation(s)
- Chih-Wen Lin
- Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, I-Shou University, Kaohsiung, Taiwan
- Division of Gastroenterology and Hepatology, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
- School of Chinese Medicine, College of Chinese Medicine, and Research Center for Traditional Chinese Medicine, China Medical University, Taichung, Taiwan
| | - Yaw-Sen Chen
- Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Gin-Ho Lo
- Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, I-Shou University, Kaohsiung, Taiwan
- Division of Gastroenterology and Hepatology, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Tsung-Chin Wu
- Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, I-Shou University, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Jen-Hao Yeh
- Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, I-Shou University, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital, School of Medicine, College of Medicine, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan
- Hepatitis Research Center, College of Medicine, and Cohort Research Center and Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital, School of Medicine, College of Medicine, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan
- Hepatitis Research Center, College of Medicine, and Cohort Research Center and Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital, School of Medicine, College of Medicine, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan
- Hepatitis Research Center, College of Medicine, and Cohort Research Center and Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital, School of Medicine, College of Medicine, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan
- Hepatitis Research Center, College of Medicine, and Cohort Research Center and Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Lewis Roberts
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Dae Won Jun
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hanyang University Seoul Hospital, Seoul, Korea
| | - Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Satoshi Yasuda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University, Palo Alto, CA, USA.
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital, School of Medicine, College of Medicine, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan.
- Hepatitis Research Center, College of Medicine, and Cohort Research Center and Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
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Sherif ZA, Nouraie SM, Lee E, Aduli F, Brim H, Ashktorab H. Trends in the Incidence of Hepatocellular Carcinoma in Washington DC: A Single Institutional Cohort Study (1959-2013). J Natl Med Assoc 2021; 113:396-404. [PMID: 33648723 DOI: 10.1016/j.jnma.2021.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Revised: 01/15/2021] [Accepted: 02/02/2021] [Indexed: 10/22/2022]
Abstract
The African American (AA) community in Washington DC is at an elevated risk for hepatocellular carcinoma (HCC) that has a dismal prognosis. The recent rapid increase in the incidence and diagnosis of HCC and liver metastases (LM) in DC prompted us to evaluate the past six decades of this incidence and some of its underlying causes using a single institutional cohort in a hospital located in the center of the city. Electronic medical and pathology records of 454 liver cancer patients from 1959 to 2013 at Howard University Hospital (HUH) were reviewed. Demographic, clinical and pathology characteristics were examined, and statistical analysis was performed using Wilcoxon rank-sum test. Incidence of HCC rose substantially between 1959 and 2013, increasing eight-fold from 1.05 to 8.0 per 100,000 AAs. The rate of increase in the last decade was highest at 550%. Cases were disproportionately male (67.2%), and median age at diagnosis was 57 years. Towards the last decade, the most common etiology for HCC was nonalcoholic fatty liver disease (NAFLD) followed by NAFLD/HCV combination. Liver cancer was clustered in the eastern region of DC in wards 4, 5, 7, and 8. Cases of liver metastases clinically diagnosed and confirmed by biopsies increased 96.4% from 1959 to 1968 to 2009-2013. This study confirms that HCC incidence has been increasing (initially driven by HCV, and NAFLD in the latter decades) more rapidly in DC than previously believed, highlighting the impact of case definitions especially regarding NAFLD in the context of changing diagnostic approaches including the revised ICD10. The rising burden, disproportionate population distribution, and low survival rate among AAs emphasize the importance of prevention and early detection as a public health imperative.
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Affiliation(s)
- Zaki A Sherif
- Department of Biochemistry & Molecular Biology, Howard University College of Medicine, Washington, DC, USA.
| | - Seyed Mehdi Nouraie
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, USA
| | - Edward Lee
- Department of Pathology, Howard University College of Medicine, Washington, DC, USA
| | - Farshad Aduli
- Department of Medicine, Howard University Hospital, Washington, DC, USA
| | - Hassan Brim
- Department of Pathology, Howard University College of Medicine, Washington, DC, USA
| | - Hassan Ashktorab
- Department of Medicine and Cancer Center, Howard University College of Medicine, Washington, DC, USA
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Choi DT, Davila JA, Sansgiry S, David E, Singh H, El-Serag HB, Sada YHF. Factors Associated With Delay of Diagnosis of Hepatocellular Carcinoma in Patients With Cirrhosis. Clin Gastroenterol Hepatol 2021; 19:1679-1687. [PMID: 32693047 PMCID: PMC7855025 DOI: 10.1016/j.cgh.2020.07.026] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 07/02/2020] [Accepted: 07/15/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS We examined the frequency of and factors associated with delays in diagnosis of hepatocellular carcinoma (HCC) in a cohort of patients with cirrhosis in the Veterans Health Administration. METHODS In a retrospective study, we collected and analyzed data from the Veterans Health Administration's electronic health records. We used a multivariate logistic regression model to identify factors associated with a delay in diagnosis of HCC of more than 60 days following a red flag (defined as the earliest date at which a diagnosis of HCC could have been made, based on American Association for the Study of Liver Disease 2005 guidelines). We used multivariate Cox proportional hazards model to evaluate the effects of delayed diagnosis on survival, adjusting for patient and provider characteristics. RESULTS Among 655 patients with cirrhosis and a diagnosis of HCC from 2006 through 2011, 46.9% had a delay in diagnosis of more than 60 days following a red flag for HCC. Delays in diagnosis for more than 60 days were significantly associated with lack of provider adherence to the guidelines (adjusted odds ratio [OR], 4.82; 95% CI, 3.12-7.45), a diagnostic imaging evaluation instead of only measurement of alfa fetoprotein (adjusted OR, 2.63; 95% CI, 1.09-6.24), and diagnosis as an incidental finding during examination for an unrelated medical problem (compared with an HCC-related assessment) (adjusted OR, 2.26; 95% CI, 1.09-4.67). Diagnostic delays of 60 days or more were associated with lower mortality compared to patients without a delay in diagnosis (unadjusted hazard ratio, 0.57; 95% CI, 0.47-0.68 and adjusted hazard ratio, 0.63; 95% CI, 0.50-0.78). CONCLUSIONS Nearly half of veterans with cirrhosis have delays in diagnosis of HCC of 60 days or more after a red flag, defined by guidelines. Interventions are needed to improve timely follow-up of red flags for HCC and adherence to guidelines, to increase early detection of HCC.
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Affiliation(s)
- Debra T. Choi
- Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX,Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, TX
| | - Jessica A. Davila
- Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX,Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, TX
| | - Shubhada Sansgiry
- Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX,Veterans Affairs South Central Mental Illness Research Education and Clinical Center (MIRECC), Houston, TX,Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, TX
| | - Eric David
- Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX
| | - Hardeep Singh
- Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX,Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, TX
| | - Hashem B. El-Serag
- Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX,Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX,Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, TX
| | - Yvonne Hsiao-Fan Sada
- Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX,Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX,Section of Hematology and Oncology, Department of Medicine, Baylor College of Medicine, Houston, TX
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Bae H, Lee SA, Choi JW, Hwang SH, Park S, Park MS. Effectiveness of Hepatocellular Carcinoma Surveillance and an Optimal Surveillance Interval: Nationwide Cohort of Korea. Yonsei Med J 2021; 62:758-766. [PMID: 34296554 PMCID: PMC8298874 DOI: 10.3349/ymj.2021.62.8.758] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 04/28/2021] [Accepted: 05/29/2021] [Indexed: 12/24/2022] Open
Abstract
PURPOSE To assess associations between surveillance intervals in a national hepatocellular carcinoma (HCC) surveillance program and receiving curative treatment and mortality using nationwide cohort data for Korea. MATERIALS AND METHODS Using the National Health Insurance Service Database of Korea, we retrospectively identified 3201852 patients, the target population of the national HCC surveillance program, between 2008 and 2017. After exclusion, a total of 64674 HCC patients were divided based on surveillance intervals: never screened, ≤6 months (6M), 7-12 months (1Y), 13-24 months (2Y), and 25-36 months (3Y). Associations for surveillance interval with the chance to receive curative therapy and all-cause mortality were analyzed. RESULTS The 6M group (51.9%) received curative therapy more often than the other groups (1Y, 48.3%; 2Y, 43.8%; 3Y, 41.3%; never screened, 34.5%). Odds ratio for receiving curative therapy among the other surveillance interval groups (1Y, 0.87; 2Y, 0.76; 3Y, 0.77; never screened, 0.57; p<0.001) were significantly lower than that of the 6M group. The hazard ratios (HRs) of all-cause mortality were 1.07, 1.14, and 1.37 for 2Y, 3Y, and never screened groups. The HR for the 1Y group (0.96; p=0.092) was not significantly different, and it was lower (0.91; p<0.001) than that of the 6M group after adjustment for lead-time bias. Curative therapy was associated with survival benefits (HR, 0.26; p<0.001). CONCLUSION HCC surveillance, especially at a surveillance interval of 6 months, increases the chance to receive curative therapy.
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Affiliation(s)
- Heejin Bae
- Department of Radiology and Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Korea
| | - Sang Ah Lee
- Big Data Strategy Department, National Health Insurance Service, Wonju, Korea
| | - Jong Won Choi
- Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Korea
| | - Shin Hye Hwang
- Department of Radiology, Yongin Severance Hospital, Yongin, Korea
| | - Sumi Park
- Department of Radiology, National Health Insurance Service Ilsan Hospital, Goyang, Korea.
| | - Mi Suk Park
- Department of Radiology and Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Korea.
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