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Liang H, Yang M, Luo D, Wu YK. Improving Adherence of Young Male Patients with HBV Infection to the Regular Follow-Up via Mobile Healthcare Platform Might Be Cost-Effective to Decrease the Morbidity of Advanced Liver Cancer. Patient Prefer Adherence 2024; 18:2581-2595. [PMID: 39717819 PMCID: PMC11665142 DOI: 10.2147/ppa.s497831] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Accepted: 12/13/2024] [Indexed: 12/25/2024] Open
Abstract
Background Young adults contribute substantially to the social economy. However, the number of young adults with liver cancer has increased recently. In addition, the mortality rate of these patients is high. Methods This retrospective study investigated the risk factors of young patients diagnosed with liver cancer over the past 12 years. Results The risk factors of liver cancer, including male, HBV infection, and family history of diseases, were more common in young patients. Nearly 80% of young patients (198/253) were tested as positive HBsAg. However, most of these patients did not visit doctors regularly, as recommended. Thus, 55.7% of young patients were diagnosed with advanced liver cancer. The aspartate aminotransferase (AST) levels were independently associated with advanced liver cancer (OR = 4.262, 95% CI = 1.559-11.65, P = 0.005) in the multivariable logistic regression. The 1-year survival rate of these patients was 19.4%. Conclusion The high-risk factors of liver cancer are common in young patients. The poor adherence to regularly visited doctors in young patients might contribute to the high ratio of advanced liver cancer. The 1-year survival rate of these patients is low. Improving patient's adherence via mobile healthcare platform and monitoring serum AST levels might decrease the incidence and mortality of liver cancer in young adults.
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Affiliation(s)
- Hao Liang
- Department of Hepatobiliary Surgery, Suining Central Hospital, Suining, Sichuan Province, People’s Republic of China
| | - Min Yang
- Department of Hepatobiliary Surgery, Suining Central Hospital, Suining, Sichuan Province, People’s Republic of China
| | - Dan Luo
- Department of Hepatobiliary Surgery, Suining Central Hospital, Suining, Sichuan Province, People’s Republic of China
| | - Ya-Kun Wu
- Department of Hepatobiliary Surgery, Suining Central Hospital, Suining, Sichuan Province, People’s Republic of China
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Xu S, Qiu L, Xu L, Liu Y, Zhang J. Development and validation of a nomogram for assessing hepatocellular carcinoma risk after SVR in hepatitis C patients with advanced fibrosis and cirrhosis. Infect Agent Cancer 2024; 19:17. [PMID: 38664813 PMCID: PMC11046761 DOI: 10.1186/s13027-024-00578-3] [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: 09/06/2023] [Accepted: 04/11/2024] [Indexed: 04/28/2024] Open
Abstract
BACKGROUND Hepatitis C patients with advanced fibrosis or cirrhosis are at high risk of developing hepatocellular carcinoma (HCC), even after sustained virological response (SVR). Clinical recommendations impose a significant burden on patients by recommending lifelong screening for HCC every six months. The goals of this study were to develop a nomogram that accurately stratifies risk of HCC and improve the screening approach that is currently in use. METHOD Risk factors for HCC were identified using univariate and multivariate analyses in this prospective study. We developed and validated a nomogram for assessing hepatocellular carcinoma risk after SVR in patients with advanced fibrosis and cirrhosis. RESULTS During the median follow-up period of 61.00 (57.00-66.00) months in the derivation cohort, 37 patients (9.61%) developed HCC. Older age (HR = 1.08, 95% CI 1.02-1.14, p = 0.009), male gender (HR = 2.38, 95% CI 1.10-5.13, p = 0.027), low serum albumin levels (HR = 0.92, 95% CI 0.86-1.00, p = 0.037), and high liver stiffness measurement (LSM) (HR = 1.03, 95% CI 1.01-1.06, p = 0.001) were found to be independent predictors of HCC development. Harrell's C-index for the derivation cohort was 0.81. The nomogram's 3-, 5- and 7-years time-dependent AUROCSs were 0.84 (95% CI 0.80-0.88), 0.83 (95% CI 0.79-0.87), and 0.81 (95% CI 0.77-0.85), respectively (all p > 0.05). According to the nomogram, patients are categorized as having low, intermediate, or high risk. The annual incidence rates of HCC in the three groups were 0.18%, 1.29%, and 4.45%, respectively (all p < 0.05). CONCLUSIONS Older age, male gender, low serum albumin levels, and high LSM were risk factors for HCC after SVR in hepatitis C patients with advanced fibrosis and cirrhosis. We used these risk factors to establish a nomogram. The nomogram can identify a suitable screening plan by classifying hepatitis C patients according to their risk of HCC.
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Affiliation(s)
- Shanshan Xu
- The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People's Republic of China
| | - Lixia Qiu
- The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People's Republic of China
| | - Liang Xu
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin Research Institute of Liver Diseases, Tianjin, 300192, People's Republic of China
| | - Yali Liu
- The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People's Republic of China
| | - Jing Zhang
- The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People's Republic of China.
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Izzo F, Mason MC, Silberfein EJ, Massarweh NN, Hsu C, Tran Cao HS, Palaia R, Piccirillo M, Belli A, Patrone R, Fusco R, Granata V, Curley SA. Long-Term Survival and Curative-Intent Treatment in Hepatitis B or C Virus-Associated Hepatocellular Carcinoma Patients Diagnosed during Screening. BIOLOGY 2022; 11:biology11111597. [PMID: 36358298 PMCID: PMC9687526 DOI: 10.3390/biology11111597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Revised: 10/24/2022] [Accepted: 10/31/2022] [Indexed: 11/06/2022]
Abstract
Background: We initiated a prospective screening trial in patients with hepatitis to diagnose HCC in the early stage and to evaluate the impact on long-term survival. Methods: From 1993−2006, 10,372 patients with chronic hepatitis B (14%), hepatitis C (81%), or both (5%) were enrolled in an HCC screening program. All patients underwent liver biopsy at enrollment. Transabdominal ultrasonography and serum alpha-fetoprotein were evaluated every 6 months. Abnormal screening results led to axial imaging and tumor biopsy. Results: Cirrhosis was confirmed on biopsy in 2074 patients (20%). HCC was diagnosed in 1016 patients (9.8%), all of whom had cirrhosis (49.0% HCC incidence in patients with cirrhosis). HCC was diagnosed at the initial screening in 165 patients (16.2%) and on follow-up in 851 patients (83.8%). The HCC diagnosis median time during follow-up screening was 6 years (range 4−10). Curative-intent treatment (resection, ablation, or transplant) was performed in 713 patients (70.2%). Overall survival at 5 and 10 years in those 713 patients was 30% and 4%, respectively, compared to no 5-year survivors in the 303 patients with advanced-stage disease (p < 0.001). Cause of death at 5 years in the 713 patients treated with curative intent was HCC in 371 patients (52%), progressive cirrhosis in 116 patients (16%), and other causes in 14 patients (2%). At 10 years, 456 patients (64%) had died from HCC, 171 (24%) from progressive cirrhosis, and 57 (8%) from other causes. Conclusions: Our screening program diagnosed early-stage HCC, permitting curative-intent treatment in 70%, but the 10-year survival rate is 4% due to HCC recurrence and progressive cirrhosis.
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Affiliation(s)
- Francesco Izzo
- Department of Surgical Oncology, IRCCS Fondazione “G. Pascale” National Cancer Institute, 80131 Naples, Italy
| | - Meredith C. Mason
- Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
| | - Eric J. Silberfein
- Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
| | - Nader N. Massarweh
- Surgical and Perioperative Care, Atlanta VA Health Care System, Decatur, GA 30033, USA
- Division of Surgical Oncology, Department of Surgery, Emory University School of Medicine, Atlanta, GA 30307, USA
- Department of Surgery, Morehouse School of Medicine, Atlanta, GA 30310, USA
| | - Cary Hsu
- Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
| | - Hop S. Tran Cao
- Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
| | - Raffaele Palaia
- Department of Surgical Oncology, IRCCS Fondazione “G. Pascale” National Cancer Institute, 80131 Naples, Italy
| | - Mauro Piccirillo
- Department of Surgical Oncology, IRCCS Fondazione “G. Pascale” National Cancer Institute, 80131 Naples, Italy
| | - Andrea Belli
- Department of Surgical Oncology, IRCCS Fondazione “G. Pascale” National Cancer Institute, 80131 Naples, Italy
| | - Renato Patrone
- Department of Surgical Oncology, IRCCS Fondazione “G. Pascale” National Cancer Institute, 80131 Naples, Italy
| | - Roberta Fusco
- Medical Oncolody Division, Igea SpA, 80013 Naples, Italy
- Italian Society of Medical and Interventional Radiology (SIRM), SIRM Foundation, via della Signora 2, 20122 Milan, Italy
| | - Vincenza Granata
- Division of Radiology, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, 80131 Naples, Italy
- Correspondence:
| | - Steven A. Curley
- Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
- Oncology Institute, Christus Trinity Mother Frances Health System, Tyler, TX 75702, USA
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Elevated CDK5R1 predicts worse prognosis in hepatocellular carcinoma based on TCGA data. Biosci Rep 2021; 41:227408. [PMID: 33346796 PMCID: PMC7791553 DOI: 10.1042/bsr20203594] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Revised: 12/15/2020] [Accepted: 12/15/2020] [Indexed: 12/13/2022] Open
Abstract
Background: Hepatocellular carcinoma (HCC) is a malignant tumor with rapid progression, high recurrence rate and poor prognosis. The objective of our investigation was to explore the prognostic value of CDK5R1 in HCC. Methods: The raw data of HCC raw data were downloaded from The Cancer Genome Atlas (TCGA) database. The Wilcoxon signed-rank test, Kruskal–Wallis test and logistic regression were applied to investigate the relevance between the CDK5R1 expression and clinicopathologic characteristics in HCC. Kaplan–Meier and Cox regression analysis were employed to examine the association between clinicopathologic features and survival. Gene set enrichment analysis (GSEA) was applied to annotate the biological function of CDK5R1. Results: CDK5R1 was highly expressed in HCC tissues. The high expression of CDK5R1 in HCC tissues was significantly associated with tumor status (P=0.00), new tumor event (P=0.00), clinical stage (P=0.00) and topography (P=0.00). Elevated CDK5R1 had significant correlation with worse overall survival (OS; P=7.414e−04), disease-specific survival (DSS; P=5.642e−04), disease-free interval (DFI; P=1.785e−05) and progression-free interval (PFI; P=2.512e−06). Besides, univariate and multivariate Cox regression analysis uncovered that increased CDK5R1 can independently predict adverse OS (P=0.037, hazard ratio [HR]= 1.7 (95% CI [1.0–2.7])), DFI (P=0.007, hazard ratio [HR]= 3.0 (95% CI [1.4–6.7])), PFI (P=0.007, hazard ratio [HR]= 2.8 (95% CI [1.3–5.9])). GSEA disclosed that notch signaling pathway and non-small cell lung cancer were prominently enriched in CDK5R1 high expression phenotype. Conclusions: Increased CDK5R1 may act as a promising independent prognostic factor of poor survival in HCC.
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Lim ES, Kim SM, Shin SS, Heo SH, Lee JE, Jeong YY. Diagnostic Performance of Simulated Abbreviated MRI for Early-Stage Hepatocellular Carcinoma Screening: A Comparison to Conventional Dynamic Contrast-Enhanced MRI. JOURNAL OF THE KOREAN SOCIETY OF RADIOLOGY 2021; 82:1218-1230. [PMID: 36238402 PMCID: PMC9432351 DOI: 10.3348/jksr.2020.0172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Revised: 10/27/2020] [Accepted: 10/30/2020] [Indexed: 12/24/2022]
Abstract
Purpose To compare the per-patient diagnostic performance of simulated abbreviated MRI (AMRI) to that of conventional MRI (CMRI) with full-sequence dynamic gadoxetic acid (GA) enhancement for early-stage hepatocellular carcinoma (HCC) screening in high-risk patients. Materials and Methods A total of 201 consecutive patients at high-risk for HCC, who underwent 3T liver MRI, were included in this retrospective study. The AMRI protocol comprised T2-weighted imaging, hepatobiliary phase imaging after GA injection, and diffusion-weighted imaging. For each patient, two AMRI and CMRI image sets were independently reviewed by two radiologists. Inter-reader agreement was assessed using Cohen's kappa value. A composite reference standard was used to determine the diagnostic performance of each image set for each reader. Results A total of 93 HCCs were detected in 79 patients. The inter-reader agreement was almost perfect for both image sets (κ = 0.839, 0.948). In AMRI, the per-patient sensitivity and negative predictive values (NPV) were 94.9% and 96.4%, respectively. In CMRI, the per-patient sensitivity and NPV were 96.2% and 97.5%, respectively. Conclusion AMRI, using only three sequences, had a comparable diagnostic performance to CMRI in screening early-stage HCC. AMRI could be an alternative HCC screening tool for high-risk HCC patients.
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Affiliation(s)
- Eun Sol Lim
- Department of Radiology, Chonnam National University Hospital, Gwangju, Korea
| | - Sung Mo Kim
- Department of Radiology, Chonnam National University Hospital, Gwangju, Korea
| | - Sang Soo Shin
- Department of Radiology, Chonnam National University Hospital, Gwangju, Korea
| | - Suk Hee Heo
- Department of Radiology, Chonnam National University, Hwasun Hospital, Hwasun, Korea
| | - Jong Eun Lee
- Department of Radiology, Chonnam National University Hospital, Gwangju, Korea
| | - Yong Yeon Jeong
- Department of Radiology, Chonnam National University, Hwasun Hospital, Hwasun, Korea
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External validation of the Toronto hepatocellular carcinoma risk index in Turkish cirrhotic patients. Eur J Gastroenterol Hepatol 2020; 32:882-888. [PMID: 32395972 DOI: 10.1097/meg.0000000000001685] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Toronto hepatocellular carcinoma risk index is developed to stratify cirrhotic patients according to 10-year hepatocellular carcinoma risk. We aimed to validate the performance of Toronto hepatocellular carcinoma risk index in a large Turkish cohort. MATERIALS AND METHODS We retrospectively reviewed the database of 1287 cirrhotic patients followed-up in a 10-year period (February 2008 to January 2018). All patients were stratified into three groups based on the Toronto hepatocellular carcinoma risk index score as follows: low-risk, < 120; intermediate risk, 120 to 240; and high risk, > 240. Area under the curve and optimal cutoff value of Toronto hepatocellular carcinoma risk index were obtained from receiver operator curve. To reveal the parameters related with hepatocellular carcinoma development, logistic regression analysis was conducted. The cumulative incidences of hepatocellular carcinoma were calculated using the Kaplan-Meier method, and the curves were compared using the log-rank test. RESULTS Out of 403 enrolled patients, 57 developed hepatocellular carcinoma. The median Toronto hepatocellular carcinoma risk index value was higher in hepatocellular carcinoma (+) group comparing to hepatocellular carcinoma (-) group [267 (70-366) vs. 224 (36-366), P < 0.001]. Out of 57 detected hepatocellular carcinomas, 45 (78.9%) were high risk, 11 (19.3%) were intermediate risk, and only one (1.8%) was low risk at the entry. The area under the curve of the Toronto hepatocellular carcinoma risk index to predict hepatocellular carcinoma was 0.750 (95% confidence interval, 0.683-0.817, P < 0.001). The optimal cutoff value of Toronto hepatocellular carcinoma risk index was 239.5, giving a sensitivity of 78.9% and specificity of 62.7%. As a result, Toronto hepatocellular carcinoma risk index remained to be the only significant parameter that has an affect on hepatocellular carcinoma development [adjusted-odds ratio: 1.016 (95% confidence interval, 1.007-1.024), P<0.001]. CONCLUSION The present study validated the performance of Toronto hepatocellular carcinoma risk index in Turkish cirrhotic patients to predict hepatocellular carcinoma risk, which can be considered as a tool for personalized surveillance.
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Coffin CS, Fung SK, Alvarez F, Cooper CL, Doucette KE, Fournier C, Kelly E, Ko HH, Ma MM, Martin SR, Osiowy C, Ramji A, Tam E, Villeneuve JP. Management of Hepatitis B Virus Infection: 2018 Guidelines from the Canadian Association for the Study of Liver Disease and Association of Medical Microbiology and Infectious Disease Canada. CANADIAN LIVER JOURNAL 2018; 1:156-217. [PMID: 35992619 PMCID: PMC9202759 DOI: 10.3138/canlivj.2018-0008] [Citation(s) in RCA: 63] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2018] [Accepted: 04/17/2018] [Indexed: 08/01/2023]
Abstract
Hepatitis B virus (HBV) infection is an important public health problem in Canada. In keeping with evolving evidence and understanding of HBV pathogenesis, the Canadian Association for the Study of Liver Disease periodically publishes HBV management guidelines. The goals of the 2018 guidelines are to (1) highlight the public health impact of HBV infection in Canada and the need to improve diagnosis and linkage to care, (2) recommend current best-practice guidelines for treatment of HBV, (3) summarize the key HBV laboratory diagnostic tests, and (4) review evidence on HBV management in special patient populations and include more detail on management of HBV in pediatric populations. An overview of novel HBV tests and therapies for HBV in development is provided to highlight the recent advances in HBV clinical research. The aim and scope of these guidelines are to serve as an up-to-date, comprehensive resource for Canadian health care providers in the management of HBV infection.
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Affiliation(s)
- Carla S. Coffin
- Cumming School of Medicine, University of Calgary, Calgary, Alberta
| | - Scott K. Fung
- Faculty of Medicine, University of Toronto, Toronto, Ontario
| | - Fernando Alvarez
- Centre hospitalier de l’université de Montréal (CHUM)—CHU Sainte-Justine, Montreal, Québec
| | - Curtis L. Cooper
- Division of Infectious Diseases, Department of Medicine, University of Ottawa, Ottawa, Ontario
| | - Karen E. Doucette
- Division of Infectious Diseases, University of Alberta, Edmonton, Alberta
| | - Claire Fournier
- Department of Medicine, Université de Montréal, Montreal, Québec
| | - Erin Kelly
- Division of Gastroenterology, Department of Medicine, University of Ottawa, Ottawa, Ontario
| | - Hin Hin Ko
- Faculty of Medicine, University of British Columbia, Vancouver, British Columbia
| | - Mang M Ma
- Division of Gastroenterology, University of Alberta, Edmonton, Alberta
| | | | - Carla Osiowy
- Viral Hepatitis and Bloodborne Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba
| | - Alnoor Ramji
- St. Paul’s Hospital, Vancouver, British Columbia
| | - Edward Tam
- LAIR Centre, Vancouver, British Columbia
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Kang HY, Choi YK, Jeong YI, Choi KC, Hyun SH, Hwang WS, Jeung EB. Immortalization of Porcine 11β-Hydroxysteroid Dehydrogenase Type 1-Transgenic Liver Cells Using SV40 Large T Antigen. Int J Mol Sci 2017; 18:ijms18122625. [PMID: 29206210 PMCID: PMC5751228 DOI: 10.3390/ijms18122625] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2017] [Revised: 11/30/2017] [Accepted: 12/02/2017] [Indexed: 12/12/2022] Open
Abstract
Cortisol is a steroid hormone essential to the maintenance of homeostasis that is released in response to stress and low blood glucose concentration. Cortisol is converted from cortisone by 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1). It has been reported that too much cortisol or overexpression of HSD11B1 induces obesity and the insulin resistance that accompanies metabolic syndrome in rodent adipose tissue. In our previous study, HSD11B1-transgenic (TG) fibroblasts were established, and a porcine model was generated by SCNT using those fibroblasts. Hepatocytes overexpressing HSD11B1 were obtained from livers of this porcine model and cultured in vitro. However, the primary hepatocytes were found to have a short life span or low proliferation rate. To overcome these problems, the SV40 large T antigen was transduced into primary HSD11B1-TG hepatocytes, and those cells were immortalized. Immortalized HSD11B1-TG hepatocytes showed restored morphology, more rapid proliferation rate, and more expression of HSD11B1 than primary hepatocytes. As well, these cells kept the hepatic characteristics such as gluconeogenic response to cortisone and increased expression of hepatic makers. The immortalized HSD11B1-TG hepatocytes may be useful for studying traits and potential therapeutic drugs for treatment of metabolic disorders induced by overexpression of HSD11B1.
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Affiliation(s)
- Hee Young Kang
- College of Veterinary Medicine, Chungbuk National University, 1 Chungdae-ro, Seowon-gu, Cheongju, Chungbuk 28644, Korea.
- Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, Korea.
| | - Young-Kwon Choi
- College of Veterinary Medicine, Chungbuk National University, 1 Chungdae-ro, Seowon-gu, Cheongju, Chungbuk 28644, Korea.
| | - Yeon Ik Jeong
- Sooam Biotech Research Foundation, 64 Kyunginro, Guro-gu, Seoul 08359, Korea.
| | - Kyung-Chul Choi
- College of Veterinary Medicine, Chungbuk National University, 1 Chungdae-ro, Seowon-gu, Cheongju, Chungbuk 28644, Korea.
| | - Sang-Hwan Hyun
- College of Veterinary Medicine, Chungbuk National University, 1 Chungdae-ro, Seowon-gu, Cheongju, Chungbuk 28644, Korea.
| | - Woo-Suk Hwang
- Sooam Biotech Research Foundation, 64 Kyunginro, Guro-gu, Seoul 08359, Korea.
| | - Eui-Bae Jeung
- College of Veterinary Medicine, Chungbuk National University, 1 Chungdae-ro, Seowon-gu, Cheongju, Chungbuk 28644, Korea.
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Sharma SA, Kowgier M, Hansen BE, Brouwer WP, Maan R, Wong D, Shah H, Khalili K, Yim C, Heathcote EJ, Janssen HLA, Sherman M, Hirschfield GM, Feld JJ. Toronto HCC risk index: A validated scoring system to predict 10-year risk of HCC in patients with cirrhosis. J Hepatol 2017; 68:S0168-8278(17)32248-1. [PMID: 28844936 DOI: 10.1016/j.jhep.2017.07.033] [Citation(s) in RCA: 130] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2016] [Revised: 07/08/2017] [Accepted: 07/29/2017] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS Current guidelines recommend biannual surveillance for hepatocellular carcinoma (HCC) in all patients with cirrhosis, regardless of etiology. However, HCC incidence is not well established for many causes of cirrhosis. We aimed to assess the disease-specific incidence of HCC in a large cohort of patients with cirrhosis and to develop a scoring system to predict HCC risk. METHODS A derivation cohort of patients with cirrhosis diagnosed by biopsy or non-invasive measures was identified through retrospective chart review. The disease-specific incidence of HCC was calculated according to etiology of cirrhosis. Factors associated with HCC were identified through multivariable Cox regression and used to develop a scoring system to predict HCC risk. The scoring system was evaluated in an external cohort for validation. RESULTS Of 2,079 patients with cirrhosis and ≥6months follow-up, 226 (10.8%) developed HCC. The 10-year cumulative incidence of HCC varied by etiologic category from 22% in patients with viral hepatitis, to 16% in those with steatohepatitis and 5% in those with autoimmune liver disease (p<0.001). By multivariable Cox regression, age, sex, etiology and platelets were associated with HCC. Points were assigned in proportion to each hazard ratio to create the Toronto HCC Risk Index (THRI). The 10-year cumulative HCC incidence was 3%, 10% and 32% in the low-risk (<120points), medium-risk (120-240) and high-risk (>240) groups respectively, values that remained consistent after internal validation. External validation was performed on a cohort of patients with primary biliary cirrhosis, hepatitis B viral and hepatitis C viral cirrhosis (n=1,144), with similar predictive ability (Harrell's c statistic 0.77) in the validation and derivation cohorts. CONCLUSION HCC incidence varies markedly by etiology of cirrhosis. The THRI, using readily available clinical and laboratory parameters, has good predictive ability for HCC in patients with cirrhosis, and has been validated in an external cohort. This risk score may help to guide recommendations regarding HCC surveillance among patients with cirrhosis. LAY SUMMARY HCC incidence varies markedly depending on the underlying cause of cirrhosis. Herein, using readily available clinical and laboratory parameters we describe a risk score, THRI, which has a good predictive ability for HCC in patients with cirrhosis, and has been validated in an external cohort. This risk score may help to guide recommendations regarding HCC surveillance among patients with cirrhosis.
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Affiliation(s)
- Suraj A Sharma
- Toronto Centre for Liver Disease, University Health Network, University of Toronto, Canada
| | - Matthew Kowgier
- Toronto Centre for Liver Disease, University Health Network, University of Toronto, Canada; Dalla Lana School of Public Health, University of Toronto, Canada
| | - Bettina E Hansen
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
| | - Willem Pieter Brouwer
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
| | - Raoel Maan
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
| | - David Wong
- Toronto Centre for Liver Disease, University Health Network, University of Toronto, Canada
| | - Hemant Shah
- Toronto Centre for Liver Disease, University Health Network, University of Toronto, Canada
| | - Korosh Khalili
- Department of Medical Imaging, University Health Network, University of Toronto, Canada
| | - Colina Yim
- Toronto Centre for Liver Disease, University Health Network, University of Toronto, Canada
| | - E Jenny Heathcote
- Toronto Centre for Liver Disease, University Health Network, University of Toronto, Canada
| | - Harry L A Janssen
- Toronto Centre for Liver Disease, University Health Network, University of Toronto, Canada; Department of Gastroenterology and Hepatology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
| | - Morris Sherman
- Toronto Centre for Liver Disease, University Health Network, University of Toronto, Canada
| | - Gideon M Hirschfield
- Centre for Liver Research and NIHR Biomedical Research Unit, University of Birmingham, Birmingham, UK
| | - Jordan J Feld
- Toronto Centre for Liver Disease, University Health Network, University of Toronto, Canada.
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Cadier B, Bulsei J, Nahon P, Seror O, Laurent A, Rosa I, Layese R, Costentin C, Cagnot C, Durand-Zaleski I, Chevreul K. Early detection and curative treatment of hepatocellular carcinoma: A cost-effectiveness analysis in France and in the United States. Hepatology 2017; 65:1237-1248. [PMID: 28176349 DOI: 10.1002/hep.28961] [Citation(s) in RCA: 87] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2016] [Revised: 10/20/2016] [Accepted: 11/17/2016] [Indexed: 12/17/2022]
Abstract
UNLABELLED Hepatocellular carcinoma (HCC) is the leading cause of death in patients with cirrhosis. Patients outside clinical trials seldom benefit from evidence-based monitoring. The objective of this study was to estimate the cost-effectiveness of complying with HCC screening guidelines. The economic evaluation compared surveillance of patients with cirrhosis as recommended by the guidelines ("gold-standard monitoring") to "real-life monitoring" from the health care system perspective. A Markov model described the history of the disease and treatment course including current first-line curative treatment: liver resection, radiofrequency ablation (RFA), and liver transplantation. Transition probabilities were derived mainly from two French cohorts, CIRVIR and CHANGH. Costs were computed using French and U.S. tariffs. Effectiveness was measured in life years gained (LYG). An incremental cost-effectiveness ratio (ICER) was calculated for a 10-year horizon and tested with one-way and probabilistic sensitivity analyses. The cost difference between the two groups was $648 ($87,476 in the gold-standard monitoring group vs. $86,829 in the real-life monitoring group) in France and $11,965 ($93,795 vs. $81,829) in the United States. Survival increased by 0.37 years (7.18 vs. 6.81 years). The ICER was $1,754 per LYG in France and $32,415 per LYG in the United States. The health gain resulted from earlier diagnosis and access to first-line curative treatments, among which RFA provided the best value for money. CONCLUSION Our results indicate that gold-standard monitoring for patients with cirrhosis is cost-effective, attributed to a higher probability of benefiting from a curative treatment and so a higher survival probability. (Hepatology 2017;65:1237-1248).
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Affiliation(s)
- Benjamin Cadier
- AP-HP, Health economics research unit, Paris, France.,ECEVE, UMRS 1123, French National Institute of Health and Medical Research, Paris, France
| | - Julie Bulsei
- AP-HP, Health economics research unit, Paris, France
| | - Pierre Nahon
- AP-HP, Department of Hepatology, Jean Verdier hospital, Bondy, France.,French League Against Cancer; Education and Research in Health Medicine and Human Biology, University Paris 13, Sorbonne Paris Cité, Paris, France.,Unité mixte de Recherche 1162, Génomique fonctionnelle des Tumeurs solides, Institut National de la Santé et de la Recherche médicale, Paris, France
| | - Olivier Seror
- Unité mixte de Recherche 1162, Génomique fonctionnelle des Tumeurs solides, Institut National de la Santé et de la Recherche médicale, Paris, France.,AP-HP, Department of Radiology, Jean Verdier hospital, Bondy, France
| | - Alexis Laurent
- AP-HP, Department of Hepatobiliary and Digestive Surgery, Henri Mondor hospital, Creteil l, France.,University Paris-Est, Creteil, France.,Inserm U955-Creteil, France
| | - Isabelle Rosa
- CHANGH study Group, Hepatology and Gastroenterology Department, Centre Hospitalier Intercommunal de Créteil, Creteil, France
| | - Richard Layese
- AP-HP, Department of Public Health, Henri Mondor hospital, Creteil, France.,University Paris-Est, A-TVB DHU, CEpiA (Clinical Epidemiology and Aging) Unit EA4393, University Paris-Est, Creteil, France
| | | | - Carole Cagnot
- Unit for Basic and Clinical research on Viral Hepatitis, ANRS (France REcherche Nord & sud Sida-HIV Hépatites-FRENSH), Paris, France
| | - Isabelle Durand-Zaleski
- AP-HP, Health economics research unit, Paris, France.,ECEVE, UMRS 1123, French National Institute of Health and Medical Research, Paris, France.,AP-HP, Department of Public Health, Henri Mondor hospital, Creteil, France
| | - Karine Chevreul
- AP-HP, Health economics research unit, Paris, France.,ECEVE, UMRS 1123, French National Institute of Health and Medical Research, Paris, France.,University Paris Diderot, Sorbonne Paris Cite, Paris, France
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11
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Diagnostic per-patient accuracy of an abbreviated hepatobiliary phase gadoxetic acid-enhanced MRI for hepatocellular carcinoma surveillance. AJR Am J Roentgenol 2015; 204:527-35. [PMID: 25714281 DOI: 10.2214/ajr.14.12986] [Citation(s) in RCA: 106] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
OBJECTIVE. The purpose of this study is to evaluate the per-patient diagnostic performance of an abbreviated gadoxetic acid-enhanced MRI protocol for hepatocellular carcinoma (HCC) surveillance. MATERIALS AND METHODS. A retrospective review identified 298 consecutive patients at risk for HCC enrolled in a gadoxetic acid-enhanced MRI-based HCC surveillance program. For each patient, the first gadoxetic acid-enhanced MRI was analyzed. To simulate an abbreviated protocol, two readers independently read two image sets per patient: set 1 consisted of T1-weighted 20-minute hepatobiliary phase and T2-weighted single-shot fast spin-echo (SSFSE) images; set 2 included diffusion-weighted imaging (DWI) and images from set 1. Image sets were scored as positive or negative according to the presence of at least one nodule 10 mm or larger that met the predetermined criteria. Agreement was assessed using Cohen kappa statistics. A composite reference standard was used to determine the diagnostic performance of each image set for each reader. RESULTS. Interreader agreement was substantial for both image sets (κ = 0.72 for both) and intrareader agreement was excellent (κ = 0.97-0.99). Reader performance for image set 1 was sensitivity of 85.7% for reader A and 79.6% for reader B, specificity of 91.2% for reader A and 95.2% for reader B, and negative predictive value of 97.0% for reader A and 96.0% for reader B. Reader performance for image set 2 was nearly identical, with only one of 298 examinations scored differently on image set 2 compared with set 1. CONCLUSION. An abbreviated MRI protocol consisting of T2-weighted SSFSE and gadoxetic acid-enhanced hepatobiliary phase has high negative predictive value and may be an acceptable method for HCC surveillance. The inclusion of a DWI sequence did not significantly alter the diagnostic performance of the abbreviated protocol.
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12
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Evaluation of serum-based cancer biomarkers: A brief review from a clinical and computational viewpoint. Crit Rev Oncol Hematol 2015; 93:103-15. [DOI: 10.1016/j.critrevonc.2014.10.002] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2013] [Revised: 08/07/2014] [Accepted: 10/01/2014] [Indexed: 12/26/2022] Open
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13
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Méndez-Sánchez N, Ridruejo E, Alves de Mattos A, Chávez-Tapia NC, Zapata R, Paraná R, Mastai R, Strauss E, Guevara-Casallas LG, Daruich J, Gadano A, Parise ER, Uribe M, Aguilar-Olivos NE, Dagher L, Ferraz-Neto BH, Valdés-Sánchez M, Sánchez-Avila JF. Latin American Association for the Study of the Liver (LAASL) clinical practice guidelines: management of hepatocellular carcinoma. Ann Hepatol 2014; 13 Suppl 1:S4-S40. [PMID: 24998696 DOI: 10.1016/s1665-2681(19)30919-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third most common cause of cancer death, and accounts for 5.6% of all cancers. Nearly 82% of the approximately 550,000 liver cancer deaths each year occur in Asia. In some regions, cancer-related death from HCC is second only to lung cancer. The incidence and mortality of HCC are increasing in America countries as a result of an ageing cohort infected with chronic hepatitis C, and are expected to continue to rise as a consequence of the obesity epidemic. Clinical care and survival for patients with HCC has advanced considerably during the last two decades, thanks to improvements in patient stratification, an enhanced understanding of the pathophysiology of the disease, and because of developments in diagnostic procedures and the introduction of novel therapies and strategies in prevention. Nevertheless, HCC remains the third most common cause of cancer-related deaths worldwide. These LAASL recommendations on treatment of hepatocellular carcinoma are intended to assist physicians and other healthcare providers, as well as patients and other interested individuals, in the clinical decision-making process by describing the optimal management of patients with liver cancer.
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Affiliation(s)
| | - Ezequiel Ridruejo
- Hepatology Section, Department of Medicine. Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno "CEMIC". Ciudad Autónoma de Buenos Aires, Argentina; Hepatology and Liver Transplant Unit. Hospital Universitario Austral, Pilar, Argentina
| | | | | | - Rodrigo Zapata
- Hepatology and Liver Transplantation Unit. University of Chile School of Medicine, German Clinic. Santiago, Chile
| | - Raymundo Paraná
- Associate Professor of School of Medicine - Federal University of Bahia Head of the Gastro-Hepatologist Unit of the University Bahia University Hospital
| | - Ricardo Mastai
- Transplantation Unit. German Hospital.Buenos Aires, Argentina
| | - Edna Strauss
- Clinical hepatologist of Hospital do Coraçao - São Paulo - Brazil. Professor of the Post Graduate Course in the Department of Pathology at the School of Medicine, University of São Paulo
| | | | - Jorge Daruich
- Hepatology Department, Clinical Hospital San Martín. University of Buenos Aires Buenos Aires, Argentina
| | - Adrian Gadano
- Section of Hepatology, Italian Hospital of Buenos Aires. Buenos Aires, Argentina
| | - Edison Roberto Parise
- Professor Associado da Disciplina de Gastroenterologia da Universidade Federal de São Paulo, Presidente Eleito da Sociedade Brasileira de Hepatologia
| | - Misael Uribe
- Digestive Diseases and Obesity Clinic, Medica Sur Clinic Foundation. México City, Mexico
| | - Nancy E Aguilar-Olivos
- Digestive Diseases and Obesity Clinic, Medica Sur Clinic Foundation. México City, Mexico
| | - Lucy Dagher
- Consultant Hepatologist. Metropolitan Policlinic- Caracas- Venezuela
| | - Ben-Hur Ferraz-Neto
- Director of Liver Institute - Beneficencia Portuguesa de São Paulo. Chief of Liver Transplantation Team
| | - Martha Valdés-Sánchez
- Department of Pediatric Oncology National Medical Center "Siglo XXI". Mexico City, Mexico
| | - Juan F Sánchez-Avila
- Hepatology and Liver Transplantation Department National Institute of Nutrition and Medical Sciences "Salvador Zubirán" Mexico City, Mexico
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14
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Izzo F, Piccirillo M, Albino V, Palaia R, Belli A, Granata V, Setola S, Fusco R, Petrillo A, Orlando R, Tosone G, Scordino F, Curley SA. Prospective screening increases the detection of potentially curable hepatocellular carcinoma: results in 8,900 high-risk patients. HPB (Oxford) 2013; 15:985-90. [PMID: 23607636 PMCID: PMC3843617 DOI: 10.1111/hpb.12080] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2012] [Accepted: 01/21/2013] [Indexed: 02/06/2023]
Abstract
OBJECTIVES Historically, only 10% of patients with hepatocellular carcinoma (HCC) are diagnosed with early-stage, potentially curable disease. In this study, chronic hepatitis virus-infected patients were prospectively screened to determine: (i) the proportion of patients diagnosed with potentially curable HCC, and (ii) survival following curative therapy. METHODS The study included 8900 chronic hepatitis virus-infected patients enrolled in a prospective screening programme, of whom 1335 (15.0%) were infected with hepatitis B virus (HBV), 7120 (80.0%) with hepatitis C virus (HCV), and 445 (5.0%) with both HBV and HCV. Screening was conducted every 6 months and included serum alpha-fetoprotein (AFP) measurement and ultrasonography. Curative treatments included liver transplantation, resection, radiofrequency ablation and/or ethanol injection. RESULTS Hepatocellular carcinoma was diagnosed in 765 (8.6%) patients. Of 1602 patients with cirrhosis, 758 (47.3%) developed HCC. Curative treatment was possible in 523 (68.4%) of the 765 HCC patients. Two- and 5-year rates of overall survival in the curative treatment group were 65% and 28%, respectively, compared with 10% and 0% in the advanced disease group (P < 0.001). CONCLUSIONS Prospective screening of patients at high risk for the development of HCC increases the proportion of patients diagnosed with potentially curable disease. This may result in an increase in the number of longterm survivors. Screening strategies should focus on patients with chronic HBV or HCV infection who have progressed to cirrhosis because more than 40% of these patients will develop HCC.
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Affiliation(s)
- Francesco Izzo
- Division of Surgical Oncology, G. Pascale National Cancer InstituteNaples, Italy
| | - Mauro Piccirillo
- Division of Surgical Oncology, G. Pascale National Cancer InstituteNaples, Italy
| | - Vittorio Albino
- Division of Surgical Oncology, G. Pascale National Cancer InstituteNaples, Italy
| | - Raffaele Palaia
- Division of Surgical Oncology, G. Pascale National Cancer InstituteNaples, Italy
| | - Andrea Belli
- Division of Surgical Oncology, G. Pascale National Cancer InstituteNaples, Italy
| | - Vincenza Granata
- Department of Radiology, G. Pascale National Cancer InstituteNaples, Italy
| | - Sergio Setola
- Department of Radiology, G. Pascale National Cancer InstituteNaples, Italy
| | - Roberta Fusco
- Department of Radiology, G. Pascale National Cancer InstituteNaples, Italy
| | - Antonella Petrillo
- Department of Radiology, G. Pascale National Cancer InstituteNaples, Italy
| | - Raffaele Orlando
- Department of Infectious Disease, University of Naples Federico IINaples, Italy
| | - Grazia Tosone
- Department of Infectious Disease, University of Naples Federico IINaples, Italy
| | - Fabrizio Scordino
- Department of Infectious Disease, University of Naples Federico IINaples, Italy
| | - Steven A Curley
- Department of Surgical Oncology, University of Texas MD Anderson Cancer CenterHouston, TX, USA
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15
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D’Onofrio M, Crosara S, De Robertis R, Canestrini S, Demozzi E, Gallotti A, Mucelli RP. Acoustic radiation force impulse of the liver. World J Gastroenterol 2013; 19:4841-4849. [PMID: 23946588 PMCID: PMC3740413 DOI: 10.3748/wjg.v19.i30.4841] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2013] [Revised: 04/15/2013] [Accepted: 07/19/2013] [Indexed: 02/06/2023] Open
Abstract
Acoustic radiation force impulse (ARFI) imaging is a new and promising ultrasound-based diagnostic technique that, evaluating the wave propagation speed, allows the assessment of the tissue stiffness. ARFI is implemented in the ultrasound scanner. By short-duration acoustic radiation forces (less than 1 ms), localized displacements are generated in a selected region of interest not requiring any external compression so reducing the operator dependency. The generated wave scan provides qualitative or quantitative (wave velocity values) responses. Several non-invasive methods for assessing the staging of fibrosis are used, in order to avoid liver biopsy. Liver function tests and transient elastography are non-invasive, sensitive and accurate tools for the assessment of liver fibrosis and for the discrimination between cirrhotic and non-cirrhotic liver. Many published studies analyse ARFI performance and feasibility in studying diffuse liver diseases and compare them to other diagnostic imaging modalities such as conventional ultrasonography and transient elastography. Solid focal liver lesions, both benign and malignant, are common findings during abdominal examinations. The accurate characterization and differential diagnosis are important aims of all the imaging modalities available today. Only few papers describe the application of ARFI technology in the study of solid focal liver lesions, with different results. In the present study, the existing literature, to the best of our knowledge, about ARFI application on diffuse and focal liver pathology has been evaluated and results and statistical analyses have been compared, bringing to the conclusion that ARFI can be used in the study of the liver with similar accuracy as transient elastography in diagnosing significant fibrosis or cirrhosis and has got some advantages in respect to transient elastography since it does not require separate equipment, better displays anatomical structures and measurements can be successfully carried out almost in every patient.
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16
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Yang Y, Jin L, He YL, Wang K, Ma XH, Wang J, Yan Z, Feng YL, Li YQ, Chen TY, Liu HL, Zhao YR. Hepatitis B virus infection in clustering of infection in families with unfavorable prognoses in northwest China. J Med Virol 2013; 85:1893-9. [PMID: 23934703 DOI: 10.1002/jmv.23649] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/08/2013] [Indexed: 12/22/2022]
Affiliation(s)
- Yuan Yang
- Department of Infectious Disease; the First Affiliated Hospital; Xi'an Jiao Tong University; Xi'an Shaanxi China
| | - Li Jin
- Department of Infectious Disease; the First Affiliated Hospital; Xi'an Jiao Tong University; Xi'an Shaanxi China
| | - Ying-Li He
- Department of Infectious Disease; the First Affiliated Hospital; Xi'an Jiao Tong University; Xi'an Shaanxi China
| | - Ke Wang
- Department of Infectious Disease; the First Affiliated Hospital; Xi'an Jiao Tong University; Xi'an Shaanxi China
| | - Xiao-Hua Ma
- Department of Infectious Disease; the Eighth Hospital; Xi'an Shaanxi China
| | - Jing Wang
- Department of Infectious Disease; the First Affiliated Hospital; Xi'an Jiao Tong University; Xi'an Shaanxi China
| | - Zhi Yan
- Department of Infectious Disease; the First Affiliated Hospital; Xi'an Jiao Tong University; Xi'an Shaanxi China
| | - Yu-Ling Feng
- Department of Infectious Disease; the First Affiliated Hospital; Xi'an Jiao Tong University; Xi'an Shaanxi China
| | - Yong-Qin Li
- Department of Infectious Disease; Xi'an Central Hospital; Xi'an Shaanxi China
| | - Tian-Yan Chen
- Department of Infectious Disease; the First Affiliated Hospital; Xi'an Jiao Tong University; Xi'an Shaanxi China
| | - Hong-Li Liu
- Department of Infectious Disease; the First Affiliated Hospital; Xi'an Jiao Tong University; Xi'an Shaanxi China
| | - Ying-Ren Zhao
- Department of Infectious Disease; the First Affiliated Hospital; Xi'an Jiao Tong University; Xi'an Shaanxi China
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17
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Cabrera R, Fitian AI, Ararat M, Xu Y, Brusko T, Wasserfall C, Atkinson MA, Liu C, Nelson DR. Serum levels of soluble CD25 as a marker for hepatocellular carcinoma. Oncol Lett 2012. [PMID: 23205111 DOI: 10.3892/ol.2012.826] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
In a previous study, we showed that the level of soluble CD25 (sCD25) was elevated in a small series of patients with hepatocellular carcinoma (HCC). In the present study, we determined the capacity of serum levels of sCD25 to detect the presence and the early stage of HCC using a larger cohort of HCC patients and evaluated the correlation between sCD25 level and tumor burden. Serum levels of sCD25 were quantified using ELISA in patients with HCC (n=145), controls with advanced fibrosis (n=61) and healthy control subjects (n=30). The levels of sCD25 in patients with HCC (median, 6,955 pg/ml) were significantly higher than those in cirrhosis-only patients (4,310 pg/ml; P<0.0001). At a cut-off value of 2,180 pg/ml, sCD25 had a sensitivity of 92.3% and a specificity of 37.7% in detecting HCC presence [area under the curve (AUC) of 0.685; P<0.0001]. By comparison, α-fetoprotein (AFP) had a sensitivity of 53.8% and a specificity of 86.8% at a cut-off value of 32.8 ng/ml (AUC=0.755; P<0.0001) for HCC presence detection. For early HCC, the sensitivity of sCD25 was 89.6% and its specificity was 39.3% (AUC=0.630; P<0.0001) at a cut-off value of 2,859 pg/ml, while AFP had a sensitivity of 41.7% and a specificity of 82.6% at a cut-off value of 20.6 ng/ml (AUC=0.630; P=0.0257). We also found a significant positive correlation between serum levels of sCD25 and tumor stage. In the present study study, sCD25 was more effective than AFP at detecting the presence and early stages of HCC. This immune factor may hold promise as a novel predictive marker of HCC presence and may be useful in distinguishing early HCC from advanced cirrhosis, currently areas of global unmet need.
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Affiliation(s)
- Roniel Cabrera
- Section of Hepatobiliary Diseases, Department of Medicine
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18
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Personalized medicine in hepatocellular carcinoma: rationale and clinical data. ACTA ACUST UNITED AC 2011. [DOI: 10.4155/cli.11.116] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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Chang Y, Lairson DR, Chan W, Lu SN, Aoki N. Cost-effectiveness of screening for hepatocellular carcinoma among subjects at different levels of risk. J Eval Clin Pract 2011; 17:261-7. [PMID: 20874834 DOI: 10.1111/j.1365-2753.2010.01432.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
OBJECTIVE The American Association for the Study of Liver Diseases 2005 practice guidelines for management of hepatocellular carcinoma (HCC) recommends that various high-risk groups of people undergo HCC surveillance. Our study aimed to investigate whether screening for HCC among subjects with early-stage cirrhosis is more cost-effective than screening among chronic hepatitis B virus (HBV) carriers without cirrhosis. METHOD Markov-based decision models were constructed to simulate development and progression of cirrhosis and HCC in the following 2 cohorts: subjects with early-stage cirrhosis and subjects who are chronic HBV carriers but do not have cirrhosis. The models also were used to estimate the incremental cost-effectiveness ratio (ICER) for each cohort over a time horizon of 25 years. RESULTS The average cost per person was less and the average effect was greater for the cohort of chronic HBV carriers without cirrhosis than for the cohort of subjects with cirrhosis. The incremental effects for use of the screening strategy and the non-screening strategy in the 2 cohorts were 0.28 years and 0.86 years, respectively. The ICERs for the 2 cohorts were $25,578 and $15,191, respectively. The cohort of chronic HBV carriers had a greater ICER with respect to the HCC screening programme because of the smaller incremental effect. The sensitivity analyses revealed that HCC incidence and the probability of accidental diagnosis of HCC were critical parameters in the model. CONCLUSION Screening for HCC among subjects with early-stage cirrhosis is more cost-effective than screening among chronic HBV carriers who do not have cirrhosis.
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Affiliation(s)
- Yaojen Chang
- Institute for Healthcare Studies, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
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Qu KZ, Zhang K, Ma W, Li H, Wang X, Zhang X, Giles F, Lai M, Afdhal NH, Albitar M. Ubiquitin-proteasome profiling for enhanced detection of hepatocellular carcinoma in patients with chronic liver disease. J Gastroenterol Hepatol 2011; 26:751-8. [PMID: 21418304 DOI: 10.1111/j.1440-1746.2010.06491.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND AND AIM A reliable test for the detection of hepatocellular carcinoma (HCC) could improve disease management. Recent reports suggested a link between abnormalities in the ubiquitin-proteasome system (UPS) and HCC. We investigated the potential of using UPS markers, along with HCC markers, to differentiate HCC from chronic liver disease (CLD). METHODS Sera from 135 HCC and 262 CLD patients were retrospectively analyzed for levels of UPS markers (proteasome, ubiquitin, and proteasome enzymatic activities) and the conventional HCC markers alpha fetoprotein (AFP), AFP-L3, and des-gamma-carboxyprothrombin (DCP). Multivariate logistic regression analysis was used to develop a model for differentiating HCC from CLD. The model was developed using a subset of 98 HCC patients and 104 CLD patients with advanced fibrosis or cirrhosis (Metavir F3-4) and then validated using an independent set (37 HCC and 44 CLD (F3-4)). RESULTS A UPS signature model incorporating six markers (trypsin-like, caspase-like, chymotrypsin-like, and normalized chymotrypsin-like activities of proteasomes; AFP; and DCP) accurately differentiated HCC from CLD (area under the curve = 0.938 [95% confidence interval, 0.884-0.991]). When analysis was restricted to patients with tumors ≤ 3 cm, the UPS model exhibited higher sensitivity (83.1% vs 51.8%) and specificity (90.2% vs 83.7%) than the three conventional markers, with good positive predictive values (34.2% vs 15.1%). These results were confirmed in the independent validation set. CONCLUSION The UPS signature in combination with AFP and DCP provides sensitive and specific differentiation of HCC in patients with CLD. The importance of the UPS in HCC suggests that therapeutic approaches targeting the UPS should be explored.
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Affiliation(s)
- Kevin Z Qu
- Quest Diagnostics Nichols Institute, San Juan Capistrano, California 92675, USA
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21
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Huang YC, Huang CF, Chang KC, Hung SF, Wang JH, Hung CH, Chen CH, Tseng PL, Kee KM, Yen YH, Tsai PS, Tsai CC, Lu SN. Community-based screening for hepatocellular carcinoma in elderly residents in a hepatitis B- and C-endemic area. J Gastroenterol Hepatol 2011; 26:129-34. [PMID: 21175806 DOI: 10.1111/j.1440-1746.2010.06476.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
BACKGROUND AND AIM The aim of the present study was to elucidate a reasonable model and the efficacy of hepatocellular carcinoma (HCC) screening on an elderly population. METHODS Two-stage HCC screening was conducted in a hepatitis C virus (HCV)-endemic area. First, participants underwent blood tests for hepatitis B surface antigen (HBsAg), anti-HCV antibody, serum α-fetoprotein (AFP), aspartate aminotransferase, alanine aminotransferase, and platelet count. Patients who were abnormal for any of the six markers were enrolled for second-stage ultrasonography. Suspected cases were referred for confirmation. HCC cases were followed for 4 years. All patients were linked to national mortality and cancer register databases to identify newly-developed HCC, 30 months after screening. RESULTS A total of 461 males and 541 females were screened for HCC, with 15.1% testing positive for HBsAg and 44.3% positive for anti-HCV. Among them, 619 (61.8%) met the criteria of ultrasonographic screening; 527 (85.1%) responded, and 16 confirmed HCC (male/female = 8/8, 68.8±8 years) cases were detected. All tumor diameters were less than 5 cm, and six were less than 2 cm. AFP and thrombocytopenia were two independent predictive factors of HCC. The overall survival rates of detected cases were 93.8% and 56.3% was 1 and 4 years, respectively. The only good prognostic predictor was "underwent curative treatment". Another seven non-HCC residents developed HCC after screening, and five of these were with either thrombocytopenia or AFP elevation. CONCLUSION Under economical consideration, AFP and platelet count should be feasible screening markers of risk identification. Early detection and prompt treatment results in good prognosis in an aged population.
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Affiliation(s)
- Yen-Chieh Huang
- Department of Family Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
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Shih STF, Crowley S, Sheu JC. Cost-effectiveness analysis of a two-stage screening intervention for hepatocellular carcinoma in Taiwan. J Formos Med Assoc 2010; 109:39-55. [PMID: 20123585 DOI: 10.1016/s0929-6646(10)60020-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
Abstract
BACKGROUND/PURPOSE Hepatocellular carcinoma (HCC) has been the leading cause of cancer death in Taiwan since the 1980s. A two-stage screening intervention was introduced in 1996 and has been implemented in a limited number of hospitals. The present study assessed the costs and health outcomes associated with the introduction of screening intervention, from the perspective of the Taiwanese government. The cost-effectiveness analysis aimed to assist informed decision making by the health authority in Taiwan. METHODS A two-phase economic model, 1-year decision analysis and a 60-year Markov simulation, was developed to conceptualize the screening intervention within current practice, and was compared with opportunistic screening alone. Incremental analyses were conducted to compare the incremental costs and outcomes associated with the introduction of the intervention. Sensitivity analyses were performed to investigate the uncertainties that surrounded the model. RESULTS The Markov model simulation demonstrated an incremental cost-effectiveness ratio (ICER) of NT$498,000 (US$15,600) per life-year saved, with a 5% discount rate. An ICER of NT$402,000 (US$12,600) per quality-adjusted life-year was achieved by applying utility weights. Sensitivity analysis showed that excess mortality reduction of HCC by screening and HCC incidence rates were the most influential factors on the ICERs. Scenario analysis also indicated that expansion of the HCC screening intervention by focusing on regular monitoring of the high-risk individuals could achieve a more favorable result. CONCLUSION Screening the population of high-risk individuals for HCC with the two-stage screening intervention in Taiwan is considered potentially cost-effective compared with opportunistic screening in the target population of an HCC endemic area.
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Affiliation(s)
- Sophy Ting-Fang Shih
- Deakin Health Economics, Public Health Research Policy and Evaluation Cluster, Deakin University, Victoria, Australia.
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Effect of surveillance for hepatocellular carcinoma on tumor staging and treatment decisions in Egyptian patients. Hepatol Int 2010; 4:500-6. [PMID: 20827407 DOI: 10.1007/s12072-010-9170-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2009] [Accepted: 12/20/2009] [Indexed: 12/16/2022]
Abstract
PURPOSE Egyptian hepatocellular carcinoma (HCC) patients present at advanced stages. We aimed to study the influence of surveillance versus non-surveillance on HCC staging and the potential therapeutic options. METHODS A retrospective study to evaluate the effect of surveillance on early detection of HCC among cirrhotic patients from 2003 to 2008. Patients examined every 6 months using ultrasound and α-fetoprotein (α-FP) (group A) and those diagnosed with those that present for the first time symptomatically or incidentally (group B). Groups were compared for α-FP level, tumour characteristics, severity of liver disease; tumour staging was evaluated by Okuda, CLIP and BCLC staging systems, in addition to the potential therapeutic options. RESULTS Group A comprised 122 HCC cases and group B 473. Surveillance improved HCC detection: at the stage of single nodule in 62.3% in group A versus 52.2% in group B, (P = 0.046) and reduced the percentage of HCC with portal vein thrombosis in 16.4 versus 33.8%, (P = 0.000) and the percentage of α-FP >400 ng/ml in 19.5 versus 32.6%, (P = 0.006) in groups A and B, respectively. Surveillance doubled the detection of HCC at early stage of BCLC (25.4 vs. 11.9% P = 0.000) and doubled the patients' chance for loco-regional ablation (12.3 vs. 5.9%, P = 0.015) and liver transplantation (10.7 vs. 3.2%, P = 0.001) in groups A and B, respectively. CONCLUSION HCC surveillance increases early detection of HCC and doubled the chances for curative options. Implementation of both HCC surveillance and cadaveric liver transplantation programs should be recommended in Egypt.
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Sturgeon CM, Duffy MJ, Hofmann BR, Lamerz R, Fritsche HA, Gaarenstroom K, Bonfrer J, Ecke TH, Grossman HB, Hayes P, Hoffmann RT, Lerner SP, Löhe F, Louhimo J, Sawczuk I, Taketa K, Diamandis EP. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for use of tumor markers in liver, bladder, cervical, and gastric cancers. Clin Chem 2010; 56:e1-48. [PMID: 20207771 DOI: 10.1373/clinchem.2009.133124] [Citation(s) in RCA: 139] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Updated National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for the use of tumor markers in the clinic have been developed. METHODS Published reports relevant to use of tumor markers for 4 cancer sites--liver, bladder, cervical, and gastric--were critically reviewed. RESULTS Alpha-fetoprotein (AFP) may be used in conjunction with abdominal ultrasound for early detection of hepatocellular carcinoma (HCC) in patients with chronic hepatitis or cirrhosis associated with hepatitis B or C virus infection. AFP concentrations >200 microg/L in cirrhotic patients with typical hypervascular lesions >2 cm in size are consistent with HCC. After a diagnosis of HCC, posttreatment monitoring with AFP is recommended as an adjunct to imaging, especially in the absence of measurable disease. Although several urine markers have been proposed for bladder cancer, none at present can replace routine cystoscopy and cytology in the management of patients with this malignancy. Some may, however, be used as complementary adjuncts to direct more effective use of clinical procedures. Although carcinoembryonic antigen and CA 19-9 have been proposed for use gastric cancer and squamous cell carcinoma antigen for use in cervical cancer, none of these markers can currently be recommended for routine clinical use. CONCLUSIONS Implementation of these recommendations should encourage optimal use of tumor markers for patients with liver, bladder, cervical, or gastric cancers.
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Affiliation(s)
- Catharine M Sturgeon
- Department of Clinical Biochemistry, Royal Infirmary of Edinburgh, Edinburgh, UK.
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Yoon YJ, Han KH, Kim DY. Role of serum prothrombin induced by vitamin K absence or antagonist-II in the early detection of hepatocellular carcinoma in patients with chronic hepatitis B virus infection. Scand J Gastroenterol 2010; 44:861-6. [PMID: 19391065 DOI: 10.1080/00365520902903034] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE The role of serum prothrombin induced by vitamin K absence or antagonist-II (PIVKA-II) in the early detection of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection has not yet been clearly identified. The purpose of the study was to evaluate the sensitivity and specificity of PIVKA-II, alone or in combination with alpha-fetoprotein (AFP), for the detection of HCC during surveillance, and to determine whether PIVKA-II was a significant risk factor for patient survival. MATERIAL AND METHODS During surveillance, 106 HCC cases and 100 non-HCC cases of chronic HBV infection were included. Sensitivity and specificity of AFP and PIVKA-II were obtained through cut-off values of 20 ng/ml and 40 mAU/ml, respectively. The Cox proportional hazards model was used to determine whether PIVKA-II would be a significant risk factor for patient survival. RESULTS The sensitivity rates of AFP and PIVKA-II were 57.5% (61/106) and 51.9% (55/106), respectively. Of 45 patients negative for AFP, 22 were positive for PIVKA-II. A combination of AFP and PIVKA-II increased the sensitivity to 78.3% (83/106). The specificities of AFP and PIVKA-II were 88.0% and 97.0%, respectively. PIVKA-II was not a significant risk factor for patient survival after multivariate analysis. CONCLUSIONS PIVKA-II can be used as a tumor marker for the early detection of HCC in patients with chronic HBV infection, especially in combination with AFP.
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Affiliation(s)
- Young Joon Yoon
- Department of Internal Medicine, Yonsei University College of Medicine, 250 Seongsanno, Seodaemun-gu, Seoul, Korea.
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Robotin MC, Kansil M, Howard K, George J, Tipper S, Dore GJ, Levy M, Penman AG. Antiviral therapy for hepatitis B-related liver cancer prevention is more cost-effective than cancer screening. J Hepatol 2009; 50:990-8. [PMID: 19303657 DOI: 10.1016/j.jhep.2008.12.022] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2008] [Revised: 12/19/2008] [Accepted: 12/29/2008] [Indexed: 12/27/2022]
Abstract
BACKGROUND/AIMS In Australia, Asian-born populations are 6-12 times more likely to develop hepatocellular cancer (HCC) than Australian-born individuals. We therefore, modelled the consequences of different management strategies for chronic hepatitis B (CHB) in Asian-born adults aged > or = 35 years. METHODS A Markov model compared (1) enhanced surveillance for HCC alone (HCC surveillance), or (2) enhanced HCC surveillance coupled with CHB treatment (HCC prevention) to the current practice, of low CHB treatment uptake. Patients were stratified and managed according to risk categories, based upon hepatitis B virus (HBV) viral load and alanine aminotransferase (ALT) levels. We measured costs, health outcomes [cases of HCC and deaths averted, quality-adjusted life-years (QALYs) gained] and incremental cost-effectiveness ratios (ICERs). RESULTS HCC surveillance would cost on average AU$8479 per person, compared to AU$2632 with current clinical practice and result in a gain of 0.014 QALYs (AU$401,516/QALY gained). A HCC prevention strategy would cost on average AU$14,600 per person, result in 0.923 QALYs gained (AU$12,956/QALY gained), reduce cases of cirrhosis by 52%, HCC diagnoses by 47% and CHB-related deaths by 56%, compared to current practice. CONCLUSIONS HCC prevention appears to be a cost-effective public health strategy in at-risk populations in Australia and is preferable to HCC surveillance as a cancer control strategy.
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Affiliation(s)
- Monica C Robotin
- The Cancer Council NSW, Research Strategy and Scientific Development Unit, 153 Dowling St, Woolloomooloo, NSW 2011, Sydney, Australia.
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Abstract
Hepatocellular carcinoma (HCC) is one of the commonest cancers worldwide, particularly in parts of the developing world, and is increasing in incidence. This article reviews the current modalities employed for the diagnosis of HCC, including serum markers, radiological techniques and histological evaluation, and summarises international guidelines for the diagnostic approach to HCC.
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The burden of illness associated with hepatocellular carcinoma in the United States. J Hepatol 2009; 50:89-99. [PMID: 18977551 DOI: 10.1016/j.jhep.2008.07.029] [Citation(s) in RCA: 107] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2008] [Revised: 07/15/2008] [Accepted: 07/19/2008] [Indexed: 01/12/2023]
Abstract
BACKGROUND/AIMS Despite the rising prevalence of hepatocellular carcinoma (HCC), data on its economic consequences are limited. This study was undertaken to estimate the aggregate annual financial burden associated with HCC in the United States, including healthcare costs and the value of lost productivity. METHODS Annual prevalence of HCC and incidence and survival were estimated using SEER data. The linked SEER-Medicare database was used to estimate distributions of healthcare utilization, quantities of treatment, and unit costs among 392 HCC patients. An age- and sex-matched cohort of non-cancer controls was used to estimate background non-cancer-related resource use and costs. RESULTS We determined the annual cost of HCC in the United States to be $454.9 million, with per-patient costs of $32,907. Healthcare costs and lost productivity accounted for 89.2% and 10.8% of total cost, respectively. Costs associated with localized HCC accounted for the highest portion (44.5%) of the total cost of illness, at $202.5 million. Regional, distant, and unstaged HCC accounted for 31.0%, 13.9%, and 10.6%, respectively. CONCLUSIONS Our results exhibit a considerable economic impact of HCC and substantial national spending on this disease.
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Paul SB, Sreenivas V, Gulati MS, Madan K, Gupta AK, Mukhopadhyay S, Acharya SK. Economic evaluation of a surveillance program of hepatocellular carcinoma (HCC) in India. Hepatol Int 2008; 2:231-6. [PMID: 19669309 PMCID: PMC2716843 DOI: 10.1007/s12072-008-9054-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2007] [Accepted: 01/23/2008] [Indexed: 10/22/2022]
Abstract
PURPOSE Surveillance of patients of cirrhosis of liver is practiced for early detection of HCC. No data from any developing country on cost-effectiveness of such a program are available. METHODS Economic evaluation of HCC surveillance was embedded in a prospective study undertaken to estimate the incidence of HCC in 194 cirrhotics. The protocol consisted of 6 monthly abdominal ultrasound (US) and serum alphafetoprotein (AFP) estimation, and yearly triple phase CT. Cost was estimated from the hospital and patient perspectives. Cost-effectiveness ratios for detecting a case of HCC were estimated. Modeling was done to estimate cost effectiveness with different combinations of diagnostic tests. RESULTS Cost-effectiveness ratios of HCC surveillance program per HCC case detected were estimated as US$ 280 from the hospital perspective. From patient perspective, these were US$ 9,965 for outstation and US$ 2,808 for local patients. Cost-effectiveness ratio for direct medical cost per case of HCC detected by 6 monthly US and AFP, the EASL protocol, was estimated to be US$ 1,510 in the private sector. CONCLUSION The cost of HCC surveillance program is exorbitant for India (gross national income per capita US$ 620) and possibly other low/middle income countries.
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Affiliation(s)
- Shashi Bala Paul
- Department of Radio-diagnosis, All India Institute of Medical Sciences, New Delhi, 110029 India
| | - Vishnubhatla Sreenivas
- Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, 110029 India
| | - Manpreet Singh Gulati
- Department of Radio-diagnosis, All India Institute of Medical Sciences, New Delhi, 110029 India
| | - Kaushal Madan
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, 110029 India
| | - Arun Kumar Gupta
- Department of Radio-diagnosis, All India Institute of Medical Sciences, New Delhi, 110029 India
| | - Sima Mukhopadhyay
- Department of Radio-diagnosis, All India Institute of Medical Sciences, New Delhi, 110029 India
| | - Subrat Kumar Acharya
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, 110029 India
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Racial and ethnic variations in hepatocellular carcinoma incidence within the United States. Am J Med 2008; 121:525-31. [PMID: 18501235 DOI: 10.1016/j.amjmed.2008.03.005] [Citation(s) in RCA: 65] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2008] [Revised: 02/22/2008] [Accepted: 03/04/2008] [Indexed: 12/29/2022]
Abstract
BACKGROUND The increasing incidence of hepatocellular carcinoma coupled with this cancer's high mortality is a public health problem. Delineating high-risk populations and cancer patterns can provide valuable information. This is necessary to broaden screening and surveillance guidelines related to early detection and prevention. METHODS By using data collected by the Surveillance, Epidemiology, and End Results program, a population-based cancer registry in the United States, our retrospective cohort study evaluated sex-specific, race/ethnicity-specific, and age-specific variations in hepatocellular carcinoma incidence from 1992 to 2004. RESULTS With men and women combined, the incidence of hepatocellular carcinoma among Asians was the highest, nearly double that of white Hispanics (11.0 vs 6.8 per 100,000/y), and more than 4 times higher than that of Caucasians (11.0 vs 2.6 per 100,000/y). Although male subjects demonstrated a doubling of cancer rates every 10 years from 30 to 50 years of age, female subjects reached male-comparable rates of cancer 10 to 15 years later and peaked at significantly lower values for all race and ethnic groups. CONCLUSION Marked differences in the incidence rates of hepatocellular carcinoma by sex, ethnicity, and age of diagnosis likely represent variations in risk factor distributions (eg, viral hepatitis) and possibly in host genetics or other environmental factors. An individualized approach tailored to specific risk profiles may more effectively identify treatable tumors than more general guidelines.
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Fahey BJ, Nelson RC, Bradway DP, Hsu SJ, Dumont DM, Trahey GE. In vivo visualization of abdominal malignancies with acoustic radiation force elastography. Phys Med Biol 2007; 53:279-93. [PMID: 18182703 DOI: 10.1088/0031-9155/53/1/020] [Citation(s) in RCA: 118] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The utility of acoustic radiation force impulse (ARFI) imaging for real-time visualization of abdominal malignancies was investigated. Nine patients presenting with suspicious masses in the liver (n = 7) or kidney (n = 2) underwent combined sonography/ARFI imaging. Images were acquired of a total of 12 tumors in the nine patients. In all cases, boundary definition in ARFI images was improved or equivalent to boundary definition in B-mode images. Displacement contrast in ARFI images was superior to echo contrast in B-mode images for each tumor. The mean contrast for suspected hepatocellular carcinomas (HCCs) in B-mode images was 2.9 dB (range: 1.5-4.2) versus 7.5 dB (range: 3.1-11.9) in ARFI images, with all HCCs appearing more compliant than regional cirrhotic liver parenchyma. The mean contrast for metastases in B-mode images was 3.1 dB (range: 1.2-5.2) versus 9.3 dB (range: 5.7-13.9) in ARFI images, with all masses appearing less compliant than regional non-cirrhotic liver parenchyma. ARFI image contrast (10.4 dB) was superior to B-mode contrast (0.9 dB) for a renal mass. To our knowledge, we present the first in vivo images of abdominal malignancies in humans acquired with the ARFI method or any other technique of imaging tissue elasticity.
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Affiliation(s)
- B J Fahey
- Department of Biomedical Engineering, Duke University, Durham, NC, USA
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Abstract
In Japan, hepatocellular carcinoma ranks as the fourth most common cancer and is responsible for about 40,000 deaths annually. Accordingly, the development of a screening system for its early detection will be linked to early treatment with a view to increasing survival. Algorithms for surveillance of hepatocellular carcinoma established in Japan will be useful for its early detection.
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Affiliation(s)
- Kiwamu Okita
- Social Insurance Shimonoseki Kohsei Hospital, Shimonoseki, Japan
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Arrieta O, Cacho B, Morales-Espinosa D, Ruelas-Villavicencio A, Flores-Estrada D, Hernández-Pedro N. The progressive elevation of alpha fetoprotein for the diagnosis of hepatocellular carcinoma in patients with liver cirrhosis. BMC Cancer 2007; 7:28. [PMID: 17288606 PMCID: PMC1803796 DOI: 10.1186/1471-2407-7-28] [Citation(s) in RCA: 73] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2006] [Accepted: 02/08/2007] [Indexed: 02/07/2023] Open
Abstract
Background Hepatocellular carcinoma is the most common cause of primary liver neoplasms and is one of the main causes of death in patients with liver cirrhosis. High Alpha fetoprotein serum levels have been found in 60–70% of patients with Hepatocellular carcinoma; nevertheless, there are other causes that increase this protein. Alpha fetoprotein levels ≥200 and 400 ng/mL in patients with an identifiable liver mass by imaging techniques are diagnostic of hepatocellular carcinoma with high specificity. Methods We analysed the sensitivity and specificity of the progressive increase of the levels of alpha fetoprotein for the detection of hepatocellular carcinoma in patients with liver cirrhosis. Seventy-four patients with cirrhosis without hepatocellular carcinoma and 193 with hepatic lesions diagnosed by biopsy and shown by image scans were included. Sensitivity and specificity of transversal determination of alpha fetoprotein ≥ 200 and 400 ng/mL and monthly progressive elevation of alpha fetoprotein were analysed. Areas under the ROC curves were compared. Positive and negative predictive values adjusted to a 5 and 10% prevalence were calculated. Results For an elevation of alpha fetoprotein ≥ 200 and 400 ng/mL the specificity is of 100% in both cases, with a sensitivity of 36.3 and 20.2%, respectively. For an alpha fetoprotein elevation rate ≥7 ng/mL/month, sensitivity was of 71.4% and specificity of 100%. The area under the ROC curve of the progressive elevation was significantly greater than that of the transversal determination of alpha fetoprotein. The positive and negative predictive values modified to a 10% prevalence are of: 98.8% and 96.92%, respectively; while for a prevalence of 5% they were of 97.4% and 98.52%, respectively. Conclusion The progressive elevation of alpha fetoprotein ≥7 ng/mL/month in patients with liver cirrhosis is useful for the diagnosis of hepatocellular carcinoma in patients that do not reach αFP levels ≥200 ng/mL. Prospective studies are required to confirm this observation.
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Affiliation(s)
- Oscar Arrieta
- Department of Medical Oncology, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico
- Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico
| | - Bernardo Cacho
- Department of Internal Medicine, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" (INCMNSZ), Mexico City, Mexico
| | | | - Ana Ruelas-Villavicencio
- Department of Internal Medicine, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" (INCMNSZ), Mexico City, Mexico
| | - Diana Flores-Estrada
- Department of Medical Oncology, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico
| | - Norma Hernández-Pedro
- Department of Medical Oncology, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico
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Schiødt FV, Ostapowicz G, Murray N, Satyanarana R, Zaman A, Munoz S, Lee WM. Alpha-fetoprotein and prognosis in acute liver failure. Liver Transpl 2006; 12:1776-81. [PMID: 17133565 DOI: 10.1002/lt.20886] [Citation(s) in RCA: 91] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Serum concentrations of alpha-fetoprotein (AFP), variably elevated during liver injury, have been suggested to be of prognostic importance in acute liver failure (ALF), higher values being associated with improved outcome. Using a nephelometric assay, we measured AFP in sera obtained on admission from 206 patients prospectively enrolled in the US ALF Study, and on day 3 in 162 of these patients. The AFP ratio was defined as the day 3 AFP concentration divided by that observed on day 1. Median (range) admission serum AFP in all patients was 8.1 (1-1,811) ng/mL and increased to 17.6 (1.1-1,162) ng/mL on day 3 (P < 0.001). Higher absolute levels were not associated with improved outcome. In fact, admission AFP levels were lower in survivors not receiving transplants than in those who died or were transplanted (P < 0.001), whereas there was no difference between the 2 groups on day 3 (P = 0.34). However, a rise in AFP values between day 1 and day 3 indicated a better prognosis: the AFP ratio was 2.2 (0.11-22.1) in spontaneous survivors and 0.87 (0.11-16.4) in nonsurvivors (P < 0.001). An increasing AFP level indicated by an AFP ratio >or=1 was observed in 70 of 98 (71%) survivors, whereas a ratio <1 was observed in 51 of 64 (80%) nonsurvivors. In conclusion, AFP values change dynamically during ALF. In this large prospective study, higher absolute values of AFP did not predict a favorable outcome, but a rising level of AFP over the first 3 hospital days frequently indicated survival.
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Affiliation(s)
- Frank V Schiødt
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA.
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Kemp W, Pianko S, Nguyen S, Bailey MJ, Roberts SK. Survival in hepatocellular carcinoma: impact of screening and etiology of liver disease. J Gastroenterol Hepatol 2005; 20:873-81. [PMID: 15946134 DOI: 10.1111/j.1440-1746.2005.03844.x] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIMS As the merits of screening at-risk populations for hepatocellular carcinoma (HCC) remain unclear, we compared the clinico-pathologic features and survival of patients with cirrhosis and HCC detected by screening (Group A) to that in non-screened cases (Group B). METHODS We studied cirrhotics who developed HCC between 1994 and 2002. During this period, cirrhotics managed by the Gastroenterology Unit were regularly screened at 6-12 monthly intervals while those managed by other hospital units were not. Demographic data, tumor details, treatment received and survival were recorded and compared according to screening status. RESULTS There were 96 cases identified; 41 by screening (group A) and 55 by non-screening methods (Group B). HCC in Group A were smaller (P < 0.01), more likely unilobar (P < 0.01), at an early stage (P < 0.0005) and before vascular invasion (P < 0.005) than Group B cases. The frequency of hepatic surgery and/or local ablation was higher in Group A than Group B (P = 0.001). Overall median survival of Group A was 882 days versus 99 days in Group B (P < 0.0001). One- and 3-year probabilities of survival in Group A were 89% and 38%, versus 33% and 19% in Group B (P < 0.001). Independent predictors of survival included screening, Child-Pugh score, creatinine, tumor stage and absence of alcohol as the etiology. CONCLUSIONS Screening for HCC in cirrhosis identifies tumors at an earlier stage, results in a higher chance of receiving curative treatment and possibly improves patient survival. The absence of alcoholic liver disease impacts favorably on survival.
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Affiliation(s)
- William Kemp
- Department of Gastroenterology, Alfred Hospital, Commercial Road, Prahran, Victoria 3181, Australia
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Abstract
Serological markers for hepatocellular carcinoma (HCC) are important for early diagnosis, as well as monitoring of tumour aggressiveness, treatment responsiveness, recurrence and survival. The three most common markers are total alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive AFP (AFP-L3) and protein induced by vitamin K absence or antagonist-II (PIVKA-II). Total AFP has the sensitivity of 60% and specificity of 90% for the detection of HCC. Increase in the percentage of AFP-L3 over the total AFP (>10%) is very specific for small HCC. PIVKA-II is also more specific than total AFP in detecting HCC. AFP-L3 and PIVKA-II levels correlate with tumour aggressiveness and prognosis. All three markers are useful for monitoring treatment responsiveness and tumour recurrence. Since the levels of the three markers are independent of each other, combination of measurement of two or three markers will increase the sensitivity and diagnostic accuracy. Some novel markers including glypican-3 are being extensively studied.
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Affiliation(s)
- Man-Fung Yuen
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong, China.
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Abstract
Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. Conventional diagnosis and treatment of this malignancy have been dismal and should be complemented by novel tools. The development and progress of HCC are believed to be caused by the accumulation of genetic changes resulting in altered expression of thousands of cancer-related genes, which can be measured by globe genetic analysis. Gene expression profiling of HCC has been employed to elucidate hepatocarcinogenesis and disclose molecular mechanisms underlying complex clinical features. Identifying phenotype-associated genes/profiles has impacts on current diagnosis and management strategy of HCC. In spite of some pitfalls of this technology and challenges in improving the research process, scrutinous validation of profiling data of HCC combined with other approaches will eventually benefit the patients.
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Affiliation(s)
- Lian-Hai Zhang
- Peking University School of Oncology, Beijing Cancer Hospital, Beijing Institute for Cancer Research, Beijing 100034, China
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Adams PC, Arthur MJ, Boyer TD, DeLeve LD, Di Bisceglie AM, Hall M, Levin TR, Provenzale D, Seeff L. Screening in liver disease: report of an AASLD clinical workshop. Hepatology 2004; 39:1204-12. [PMID: 15122748 DOI: 10.1002/hep.20169] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
This report summarizes an AASLD Clinical Workshop that was presented at Digestive Diseases Week 2003 on screening in liver diseases. As newer diagnostic tests become available, many liver diseases and complications of liver disease can be detected at an early asymptomatic stage. In many cases, early detection can lead to earlier treatment and an improved outcome. However, screening for liver diseases in asymptomatic persons has the potential for adverse consequences, including discrimination and stigmatization. The cost of screening programs is significant, and access to screening tests varies in different countries. Future screening programs require careful planning and implementation to balance the benefits, risks, and cost-effectiveness. This review outlines the concepts of screening and their application to a broad range of liver diseases.
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Affiliation(s)
- Paul C Adams
- London Health Sciences Centre, London, Ontario, Canada.
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Chan AOO, Yuen MF, Lam CM, Fong CY, Wong BCY, Lai CL. Prevalence and characteristics of familial hepatocellular carcinoma caused by chronic hepatitis B infection in Hong Kong. Aliment Pharmacol Ther 2004; 19:401-6. [PMID: 14871279 DOI: 10.1046/j.1365-2036.2004.01855.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/08/2022]
Abstract
BACKGROUND Hepatitis B virus infection is an important aetiological factor for hepatocellular carcinoma. Clusters of hepatocellular carcinoma have been observed in families infected with hepatitis B virus. AIM To investigate the prevalence and characteristics of hepatocellular carcinoma associated with familial hepatitis B virus in Hong Kong. METHODS Hepatitis B virus patients were screened for familial hepatocellular carcinoma using a standardized questionnaire. The clinical features of patients with familial hepatocellular carcinoma were compared with those of 118 patients with sporadic hepatocellular carcinoma attending the clinic during the same period. RESULTS A total of 5080 patients were interviewed. Validation of the questionnaire indicated that the reliability was high. There were 22 families with familial hepatocellular carcinoma, giving a prevalence of 4.3 families/1000 hepatitis B virus carriers. The mean age of onset was 48.5 +/- 13 years in familial hepatocellular carcinoma and 62 +/- 11 years in sporadic hepatocellular carcinoma (P = 0.005). The ages of onset were 59 +/- 11, 40 +/- 10 and 18 +/- 4 years in the first, second and third generations, respectively (P < 0.0001), suggesting an anticipation phenomenon. Familial hepatocellular carcinoma patients were more likely to present with pain (70% vs. 10%, P < 0.0001), but not on routine screening (14% vs. 52%, P < 0.0001), than sporadic hepatocellular carcinoma patients. CONCLUSION The prevalence of familial hepatocellular carcinoma is significant in Hong Kong. These patients show specific clinical features when compared with patients with sporadic hepatocellular carcinoma.
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Affiliation(s)
- A O O Chan
- Department of Medicine, the University of Hong Kong, Queen Mary Hospital, Hong Kong
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