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Li X, Xu Y, Ou Y, Li H, Xu W. Optimizing Treatment Selection for Early Hepatocellular Carcinoma Based on Tumor Biology, Liver Function, and Patient Status. J Hepatocell Carcinoma 2025; 12:777-790. [PMID: 40255902 PMCID: PMC12009567 DOI: 10.2147/jhc.s514248] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2024] [Accepted: 04/08/2025] [Indexed: 04/22/2025] Open
Abstract
Early-stage hepatocellular carcinoma (HCC) represents a critical window for curative treatment. However, treatment selection is complicated by significant heterogeneity in tumor biology, liver function, and patient performance status. This review provides a comprehensive overview of current curative-intent strategies for early-stage HCC, including liver transplantation, surgical resection, and local ablative therapies. We emphasize the importance of integrating tumor-specific characteristics-such as microvascular invasion, size, and anatomical location-with liver reserve metrics, including portal hypertension, Child-Pugh classification, and novel indices like albumin-bilirubin and albumin-indocyanine green evaluation grades. Furthermore, we discuss recent advances in non-thermal ablation techniques (eg, high-intensity focused ultrasound and irreversible electroporation), and technical innovations in radiofrequency ablation and cryoablation that are expanding the therapeutic landscape. By combining macro-level functional assessments with micro-level biological indicators, this review advocates for a personalized, evidence-based framework to optimize long-term outcomes in early HCC. The future of HCC management lies in standardizing individualized therapy.
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Affiliation(s)
- Xing Li
- Department of Ultrasound Diagnosis and Treatment, Tianjin Cancer Hospital Airport Hospital, National Clinical Research Center for Cancer, Tianjin, People’s Republic of China
- Department of Ultrasound Diagnosis and Treatment, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of China
| | - Yong Xu
- Department of Ultrasound Diagnosis and Treatment, Tianjin Cancer Hospital Airport Hospital, National Clinical Research Center for Cancer, Tianjin, People’s Republic of China
- Department of Ultrasound Diagnosis and Treatment, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of China
| | - Yanmei Ou
- Department of Ultrasound Diagnosis and Treatment, Tianjin Cancer Hospital Airport Hospital, National Clinical Research Center for Cancer, Tianjin, People’s Republic of China
| | - Huikai Li
- Department of Hepatobiliary Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of China
| | - Wengui Xu
- Department of Molecular Imaging and Nuclear Medicine, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of China
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Mysko C, Landi S, Purssell H, Allen AJ, Prince M, Lindsay G, Rodrigues S, Irvine J, Street O, Gahloth D, MacLennan S, Piper Hanley K, Hanley N, Athwal VS. Health inequalities in hepatocellular carcinoma surveillance, diagnosis, treatment, and survival in the United Kingdom: a scoping review. BJC REPORTS 2025; 3:13. [PMID: 40033086 DOI: 10.1038/s44276-025-00126-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 12/13/2024] [Accepted: 01/31/2025] [Indexed: 03/05/2025]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) remains a deadly cancer in the UK despite advancements in curative therapies. Societal conditions and health inequalities influence the development of chronic liver disease and outcomes from complications including HCC. Scoping this emergent evidence-base is required to inform research and solutions for the NHS. METHODS A PRISMA scoping review was performed up to September 2023. Articles exploring health inequalities in HCC involving the UK population were included. RESULTS This review has characterised axes of health inequality and their impact across the HCC care continuum in the UK. Studies predominantly employed a cohort design or population-based analyses, with meta-analyses of surveillance utilisation including only a single UK study. These methodologies provided an appropriate lens to understand longitudinal trends and identify disadvantaged groups. However, important evidence gaps remain, including exploration of patient perspectives, intersectional analyses, and statistical measures of socioeconomic inequity in HCC. CONCLUSIONS HCC is a rapidly growing cause of cancer mortality and disproportionally affects underserved groups, presenting a major public health concern. Further research is required to innovate and evaluate surveillance and management pathways to reduce systemic inequities. Direction is needed at the national level to improve prevention, early diagnosis and access to curative treatment.
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Affiliation(s)
- Christopher Mysko
- Manchester University NHS Foundation Trust, Manchester, UK
- University of Manchester, Manchester, UK
| | - Stephanie Landi
- Manchester University NHS Foundation Trust, Manchester, UK
- University of Manchester, Manchester, UK
| | - Huw Purssell
- Manchester University NHS Foundation Trust, Manchester, UK
- University of Manchester, Manchester, UK
| | - A Joy Allen
- Roche Diagnostics Limited, Welwyn Garden City, UK
| | - Martin Prince
- Manchester University NHS Foundation Trust, Manchester, UK
| | | | | | | | | | | | | | | | - Neil Hanley
- University of Birmingham, Birmingham, UK
- University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Varinder Singh Athwal
- Manchester University NHS Foundation Trust, Manchester, UK.
- University of Manchester, Manchester, UK.
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Oura K. Recent advances in systemic therapies for unresectable hepatocellular carcinoma and their impact on clinical outcomes. Hepatol Res 2025; 55:163-165. [PMID: 40317576 DOI: 10.1111/hepr.14158] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/07/2025]
Affiliation(s)
- Kyoko Oura
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kita, Kagawa, Japan
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Aralica M, Nadarevic T, Colli A, Casazza G, Vranić L, Fraquelli M, Poropat G, Štimac D. GALAD, or des-gamma-carboxy prothrombin compared with alpha-foetoprotein for the diagnosis of hepatocellular carcinoma in people with chronic liver disease. Cochrane Database Syst Rev 2024; 12:CD015826. [PMID: 39688172 PMCID: PMC11650702 DOI: 10.1002/14651858.cd015826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2024]
Abstract
This is a protocol for a Cochrane Review (diagnostic). The objectives are as follows: To estimate the diagnostic accuracy of des-gamma-carboxy prothrombin, GALAD (Gender, Age, Lens culinaris agglutinin-reactive AFP, AFP and DCP), and alpha-foetoprotein for the diagnosis of hepatocellular carcinoma of any size, and at any stage, in adults with chronic liver disease, in either a surveillance programme or a clinical setting. We acknowledge the possibility that theoretically, the accuracy of the tests in a surveillance programme may differ from that in a clinical setting due to variation in inclusion criteria and the prevalence of the target condition. However, we do not plan a separate analysis for surveillance and clinical settings, as they are not clearly distinct in current clinical practice (Forner 2018; Poustchi 2011). In routine evaluation of people with chronic liver disease, index tests, as well as ultrasound, are already part of standard procedure. Given that HCC typically presents with no symptoms and is often asymptomatic, suspicion of the disease is typically based solely on the presence of advanced chronic liver disease. However, we do plan to consider the study setting as a potential source of heterogeneity. To compare the diagnostic accuracy of des-gamma-carboxy prothrombin (DCP) alone or GALAD alone versus alpha-foetoprotein (AFP), for the diagnosis of hepatocellular carcinoma (HCC) of any size, at any stage; in adults with chronic liver disease, either in a surveillance programme or a clinical setting. Secondary objectives To estimate the diagnostic accuracy of DCP or GALAD versus AFP, for resectable HCC in people with chronic liver disease, in a surveillance programme and a clinical setting. To investigate the following predefined sources of heterogeneity for each of the index tests: study design (case-control studies compared to cross-sectional studies); inclusion of participants without cirrhosis (studies including more than 10% of participants without cirrhosis compared to studies including less than 10% of participants without cirrhosis); study location (population differences): studies conducted in North and South America and Europe compared to Asia and Africa; prevalence of the target condition (studies with hepatocellular carcinoma prevalence more than 10% compared to studies with hepatocellular carcinoma prevalence less than 10%); participant selection (participants recruited from planned surveillance programmes compared to clinical cohorts); different reference standards (histology of the explanted liver compared to liver biopsy compared to another reference standard); different aetiology: studies including at least 90% of participants with chronic viral hepatitis compared to studies including less than 90% of participants with chronic viral hepatitis.
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Affiliation(s)
- Merica Aralica
- Clinical Department of Laboratory Diagnostics, Clinical Hospital Centre Rijeka, Rijeka, Croatia
| | - Tin Nadarevic
- Department of Radiology, Clinical Hospital Centre Rijeka, Rijeka, Croatia
| | - Agostino Colli
- Department of Transfusion Medicine and Haematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Giovanni Casazza
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
| | - Luka Vranić
- Department of Gastroenterology, Clinical Hospital Centre Rijeka, Rijeka, Croatia
| | - Mirella Fraquelli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca´ Granda - Ospedale Maggiore Policlinico, Milano, Milan, Italy
| | - Goran Poropat
- Department of Gastroenterology, Clinical Hospital Centre Rijeka, Rijeka, Croatia
| | - Davor Štimac
- Department of Gastroenterology, Clinical Hospital Centre Rijeka, Rijeka, Croatia
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Effendi K, Rahadiani N, Stephanie M, Kurebayashi Y, Tsujikawa H, Jasirwan CO, Syaiful RA, Sakamoto M. Comparative Immunohistochemical Analysis of Clinicopathological Subgroups in Hepatocellular Carcinomas from Japan and Indonesia. J Clin Exp Hepatol 2024; 14:101451. [PMID: 38975604 PMCID: PMC11225344 DOI: 10.1016/j.jceh.2024.101451] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Accepted: 05/19/2024] [Indexed: 07/09/2024] Open
Abstract
Background Standardized pathological evaluation based on immunohistochemical (IHC) analysis could improve hepatocellular carcinoma (HCC) diagnoses worldwide. We evaluated differences in clinicopathological subgroups in HCCs from two academic institutions in Tokyo-Japan, and Jakarta-Indonesia. Methods Clinicopathological parameters and molecular expression patterns were evaluated in 35 HCCs from Indonesia and 41 HCCs from Japan. IHC analysis of biliary/stem cell (B/S) markers (cytokeratin 19, sal-like protein 4, epithelial cell adhesion molecule) and Wnt/β-catenin (W/B) signaling-related molecules (β-catenin, glutamine synthetase) could determine the IHC-based subgroups. For immuno-subtypes categorization, CD3/CD79α double immunohistochemistry was done to evaluate the infiltration of T and B cells. CD34 staining allowed identification of vessels that encapsulated tumor clusters (VETC). Results Indonesian HCC patients were mostly <60 years old (66%) with a hepatitis B virus (HBV) background (82%), in contrast to Japanese HCC patients (8% and 19%, respectively, both P < 0.001). In comparison with Japanese, Indonesian cases more frequently had >5 cm tumor size (74% vs 23%, P = 0.001), poor differentiation (40% vs 24%), portal vein invasion (80% vs 61%), and α-fetoprotein levels >500 ng/ml (45% vs 13%, P = 0.005). No significant differences were found in the proportions of B/S, W/B, and -/- subgroups from both countries. No immune-high tumors were observed among Indonesian cases, and immune-low tumors (66%) were more common than in Japanese cases (54%). VETC-positive tumors in Indonesia were significantly more common (29%), and most were in the HBV (90%) and -/- subgroups (90%), whereas Japanese VETC cases (10%, P = 0.030) were nonviral (100%) and W/B subgroups (75%). Conclusion IHC-based analysis more precisely reflected the clinicopathological differences of HCCs in Japan and Indonesia. These findings provide new insights into standardization attempts and HCC heterogeneity among countries.
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Affiliation(s)
- Kathryn Effendi
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Nur Rahadiani
- Department of Anatomical Pathology, Faculty of Medicine Universitas Indonesia/Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia
| | - Marini Stephanie
- Department of Anatomical Pathology, Faculty of Medicine Universitas Indonesia/Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia
| | - Yutaka Kurebayashi
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Hanako Tsujikawa
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
- Department of Diagnostic Pathology, National Hospital Organization Saitama Hospital, Saitama, Japan
| | - Chyntia O.M. Jasirwan
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia/Dr. Cipto Mangunkusmo Hospital, Jakarta, Indonesia
| | - Ridho A. Syaiful
- Division of Digestive Surgery, Department of Surgery, Faculty of Medicine Universitas Indonesia/Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia
| | - Michiie Sakamoto
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
- School of Medicine, International University of Health and Welfare, Chiba, Japan
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Takeuchi Y, Nozawa A, Yukimoto A, Kitsuka M, Tateishi R, Koike K, Okano K, Kanto T. Integrated policy of medical expense subsidies and clinical registry for patients with liver cancer and decompensated cirrhosis in Japan. Hepatol Res 2024; 54:745-752. [PMID: 38877867 DOI: 10.1111/hepr.14085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Revised: 05/24/2024] [Accepted: 06/03/2024] [Indexed: 08/03/2024]
Abstract
Chronic hepatitis B and C are among the most significant infectious diseases worldwide, and are major risk factors for liver cirrhosis and liver cancer. In Japan, comprehensive hepatitis measures are implemented for the testing and treatment of viral hepatitis, thus enabling the early diagnosis of liver cancer. Nevertheless, patients with decompensated cirrhosis and liver cancer often have unfavorable prognoses and require repetitive long-term treatment. In fiscal year 2018, an integrated policy of medical expense subsidies and research was established in Japan that aimed to alleviate patients' financial burden and launch the clinical registry of advanced liver disease. Over time, updates to the eligibility for the subsidy increased access to patients and has led to an increased number of beneficiaries. Additionally, the accumulation of clinical data in the registry has revealed the treatment choices for these diseases. However, the disparities in efforts across prefectures have also become evident. Raising public awareness of the policy and tightening the multisector healthcare network are keys to success in supporting qualifying patients with advanced liver disease.
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Affiliation(s)
- Yasue Takeuchi
- Hepatitis Information Center, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan
| | - Akinori Nozawa
- Hepatitis Prevention and Control Office, Cancer and Disease Control Division, Public Health Bureau, Labor, and Welfare, Tokyo, Japan
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Atsushi Yukimoto
- Hepatitis Prevention and Control Office, Cancer and Disease Control Division, Public Health Bureau, Labor, and Welfare, Tokyo, Japan
- Departments of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Masayuki Kitsuka
- Hepatitis Prevention and Control Office, Cancer and Disease Control Division, Public Health Bureau, Labor, and Welfare, Tokyo, Japan
- Liver Center, Saga University Hospital, Faculty of Medicine, Saga University, Saga, Japan
| | - Ryosuke Tateishi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kazuhiko Koike
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
- Kanto Central Hospital, Tokyo, Japan
| | - Kazuyuki Okano
- Hepatitis Prevention and Control Office, Cancer and Disease Control Division, Public Health Bureau, Labor, and Welfare, Tokyo, Japan
| | - Tatsuya Kanto
- Hepatitis Information Center, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan
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Wang F, Numata K, Funaoka A, Liu X, Kumamoto T, Takeda K, Chuma M, Nozaki A, Ruan L, Maeda S. Establishment of nomogram prediction model of contrast-enhanced ultrasound and Gd-EOB-DTPA-enhanced MRI for vessels encapsulating tumor clusters pattern of hepatocellular carcinoma. Biosci Trends 2024; 18:277-288. [PMID: 38866488 DOI: 10.5582/bst.2024.01112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/14/2024]
Abstract
To establish clinical prediction models of vessels encapsulating tumor clusters (VETC) pattern using preoperative contrast-enhanced ultrasound (CEUS) and gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid magnetic resonance imaging (EOB-MRI) in patients with hepatocellular carcinoma (HCC). A total of 111 resected HCC lesions from 101 patients were included. Preoperative imaging features of CEUS and EOB-MRI, postoperative recurrence, and survival information were collected from medical records. The best subset regression and multivariable Cox regression were used to select variables to establish the prediction model. The VETC-positive group had a statistically lower survival rate than the VETC-negative group. The selected variables were peritumoral enhancement in the arterial phase (AP), hepatobiliary phase (HBP) on EOB-MRI, intratumoral branching enhancement in the AP of CEUS, intratumoral hypoenhancement in the portal phase of CEUS, incomplete capsule, and tumor size. A nomogram was developed. High and low nomogram scores with a cutoff value of 168 points showed different recurrence-free survival rates and overall survival rates. The area under the curve (AUC) and accuracy were 0.804 and 0.820, respectively, indicating good discrimination. Decision curve analysis showed a good clinical net benefit (threshold probability > 5%), while the Hosmer-Lemeshow test yielded excellent calibration (P = 0.6759). The AUC of the nomogram model combining EOB-MRI and CEUS was higher than that of the models with EOB-MRI factors only (0.767) and CEUS factors only (0.7). The nomogram verified by bootstrapping showed AUC and calibration curves similar to those of the nomogram model. The Prediction model based on CEUS and EOB-MRI is effective for preoperative noninvasive diagnosis of VETC.
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Affiliation(s)
- Feiqian Wang
- Department of Ultrasound, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan
| | - Kazushi Numata
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan
| | - Akihiro Funaoka
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan
| | - Xi Liu
- Department of Pathology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Takafumi Kumamoto
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan
| | - Kazuhisa Takeda
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan
| | - Makoto Chuma
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan
| | - Akito Nozaki
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan
| | - Litao Ruan
- Department of Ultrasound, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Shin Maeda
- Division of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan
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Wang M, Liu J, Yan L, Wang J, Jin Y, Zheng ZJ. Burden of liver cancer attributable to high fasting plasma glucose: a global analysis based on the global burden of disease study 2019. J Nutr Health Aging 2024; 28:100261. [PMID: 38810511 DOI: 10.1016/j.jnha.2024.100261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Revised: 04/28/2024] [Accepted: 05/02/2024] [Indexed: 05/31/2024]
Abstract
OBJECTIVE Liver cancer is the world's sixth most prevalent cancer and the third most frequent cause of cancer-related mortality. Glucose metabolic disorders, indicated by a high fasting plasma glucose (HFPG) concentration, is a contributor to the etiology of liver cancer. With the rising prevalence of glucose metabolic disorders, an assessment of the global burden of liver cancer attributable to HFPG is warranted to inform global liver cancer prevention and control strategies. METHODS AND ANALYSIS We evaluated the global death and disability-adjusted life years (DALYs) of liver cancer and its subtypes attributable to HFPG at global, regional, and country level. The temporal trend and disparity across geographic regions, social development level, age groups and sex were assessed. RESULTS In 2019, HFPG-attributable liver cancer was estimated to have caused 4,729.49 deaths and to be responsible for 99,302.25 DALYs. The age-standardized mortality and DALY rate were 0.06 and 1.20 per 100,000 population, and displayed a significantly increasing temporal trend from 1990 to 2019. The age-standardized mortality rate of patients with liver cancer that was attributable to HFPG was higher in men than women. Sex-based disparity narrowed after the women reached menopause, but increased between 1990 and 2019. CONCLUSION The burden of liver cancer that are attributable to HFPG has been influenced by longitudinal changes in lifestyle, the etiology of liver disease, age demographics, and hormonal status in women. These findings suggest that comprehensive strategies could be implemented, especially for patients with NASH and hyperglycemia, to prevent liver cancer.
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Affiliation(s)
- Minmin Wang
- Department of Global Health, School of Public Health, Peking University, Beijing, China; Institute for Global Health and Development, Peking University, Beijing, China
| | - Jingyi Liu
- School of Nursing, Peking University, Beijing, China
| | - Liang Yan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital and Institute, Beijing, China
| | - Jia Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China
| | - Yinzi Jin
- Department of Global Health, School of Public Health, Peking University, Beijing, China; Institute for Global Health and Development, Peking University, Beijing, China.
| | - Zhi-Jie Zheng
- Department of Global Health, School of Public Health, Peking University, Beijing, China; Institute for Global Health and Development, Peking University, Beijing, China
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Nan Y, Garay OU, Lu X, Zhang Y, Xie L, Niu Z, Chen W. Early-stage hepatocellular carcinoma screening in patients with chronic hepatitis B in China: a cost-effectiveness analysis. J Comp Eff Res 2024; 13:e230146. [PMID: 38415341 PMCID: PMC11044951 DOI: 10.57264/cer-2023-0146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Accepted: 02/12/2024] [Indexed: 02/29/2024] Open
Abstract
Aim: To evaluate the cost-effectiveness of seven screening strategies for chronic hepatitis B (CHB) patients in China. Methods: A discrete event simulation model combining a decision tree and Markov structure was developed to simulate a CHB cohort aged ≥40 years on a lifetime horizon and evaluate the costs and health outcomes (quality-adjusted life years [QALYs] gained) of ultrasonography (US), alpha-fetoprotein (AFP), protein induced by vitamin K absence-II (PIVKA-II), AFP+US, AFP+PIVKA-II, GAAD (a diagnostic algorithm based on gender and age combined with results of AFP and PIVKA-II) and GAAD+US. Epidemiologic, clinical performance, utility and cost data were obtained from the literature, expert interviews and real-world data. Uncertainties on key parameters were explored through deterministic and probabilistic sensitivity analyses (DSA and PSA). Results: Compared with other strategies, GAAD+US detected the most HCC patients at early stage, and GAAD was the screening strategy with the lowest average cost per HCC case diagnosed. Using 3× China's 2022 GDP per capita ($38,233.34) as the threshold, the three strategies of US, GAAD and GAAD+US formed a cost-effectiveness frontier. Screening with US, GAAD, or GAAD+US was associated with costs of $6110.46, $7622.05 and $8636.32, and QALYs of 13.18, 13.48 and 13.52, respectively. The ICER of GAAD over US was $4993.39/QALY and the ICER of GAAD+US over GAAD was $26,691.45/QALY, which was less than 3× GDP per capita. Both DSA and PSA proved the stability of the results. Conclusion: GAAD+US was the most cost-effective strategy for early HCC diagnosis among CHB patients which could be considered as the liver cancer screening scheme for the high-risk population in China.
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Affiliation(s)
- Yuemin Nan
- Department of Traditional & Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, 050051, China
| | | | - Xianzhong Lu
- Roche Diagnostics (Shanghai) Co., Ltd, Shanghai, 200335, China
| | - Yue Zhang
- Roche Diagnostics (Shanghai) Co., Ltd, Shanghai, 200335, China
| | - Li Xie
- Yidu Cloud (Beijing) Technology Co., Ltd, Beijing, 100083, China
| | - Zhongyi Niu
- Yidu Cloud (Beijing) Technology Co., Ltd, Beijing, 100083, China
| | - Wen Chen
- School of Public Health, Fudan University, Shanghai, 200032, China
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10
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Yang B, Xi X, Yu H, Jiang H, Liang Z, Smayi A, Wu B, Yang Y. Evaluation of the effectiveness of surgical resection and ablation for the treatment of early-stage hepatocellular carcinoma: A retrospective cohort study. Cancer Rep (Hoboken) 2024; 7:e2030. [PMID: 38488487 PMCID: PMC10941592 DOI: 10.1002/cnr2.2030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2023] [Revised: 02/08/2024] [Accepted: 02/21/2024] [Indexed: 03/18/2024] Open
Abstract
BACKGROUND The optimal treatment strategy for early-stage hepatocellular carcinoma (HCC) remains controversial, specifically in regard to surgical resection (SR) and ablation. The aim of this study was to investigate the impact of SR and ablation on recurrence and prognosis in early-stage HCC patients, to optimize treatment strategies and improve long-term survival. METHODS A retrospective analysis was conducted on 801 patients diagnosed with Barcelona Clinic Liver Cancer (BCLC) stage 0/A HCC and treated with SR or ablation between January 2015 and December 2019. The effectiveness and complications of both treatments were analyzed, and patients were followed up to measure recurrence and survival. Propensity score matching (PSM) was employed to increase comparability between the two groups. The Kaplan-Meier method was used to analyze recurrence and survival, and a Cox risk proportional hazard model was used to identify risk factors that affect recurrence and surviva. RESULTS Before PSM, the overall survival (OS) rates were similar in both groups, with recurrence-free survival (RFS) rates better in the SR group than in the ablation group. After PSM, there was no significant difference in OS between the two groups. However, the RFS rates were significantly better in the SR group than in the ablation group. The ablation group exhibited superior outcomes compared to the SR group, with shorter treatment times, reduced bleeding, shorter hospital stays, and lower hospital costs. Concerning the location of the HCC within the liver, comparable efficacy was observed between SR and ablation for disease located in the noncentral region or left lobe. However, for HCCs located in the central region or right lobe of the liver, SR was more effective than ablation. CONCLUSIONS This study revealed no significant difference in OS between SR and ablation for early-stage HCC, with SR providing better RFS and ablation demonstrating better safety profiles and lower hospital costs. These findings offer valuable insights for clinicians in determining optimal treatment strategies for early-stage HCC patients, particularly in terms of balancing efficacy, safety, and cost considerations.
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Affiliation(s)
- Bilan Yang
- Department of GastroenterologyThe Third Affiliated Hospital of Sun Yat‐Sen UniversityGuangzhouPeople's Republic of China
- Guangdong Provincial Key Laboratory of Liver Disease ResearchGuangzhouGuangdongPeople's Republic of China
| | - Xiaoli Xi
- Department of GastroenterologyThe Third Affiliated Hospital of Sun Yat‐Sen UniversityGuangzhouPeople's Republic of China
- Guangdong Provincial Key Laboratory of Liver Disease ResearchGuangzhouGuangdongPeople's Republic of China
| | - Hongsheng Yu
- Department of GastroenterologyThe Third Affiliated Hospital of Sun Yat‐Sen UniversityGuangzhouPeople's Republic of China
- Guangdong Provincial Key Laboratory of Liver Disease ResearchGuangzhouGuangdongPeople's Republic of China
| | - Hao Jiang
- Department of GastroenterologyThe Third Affiliated Hospital of Sun Yat‐Sen UniversityGuangzhouPeople's Republic of China
- Guangdong Provincial Key Laboratory of Liver Disease ResearchGuangzhouGuangdongPeople's Republic of China
| | - Zixi Liang
- Department of GastroenterologyThe Third Affiliated Hospital of Sun Yat‐Sen UniversityGuangzhouPeople's Republic of China
- Guangdong Provincial Key Laboratory of Liver Disease ResearchGuangzhouGuangdongPeople's Republic of China
| | - Abdukyamu Smayi
- Department of GastroenterologyThe Third Affiliated Hospital of Sun Yat‐Sen UniversityGuangzhouPeople's Republic of China
- Guangdong Provincial Key Laboratory of Liver Disease ResearchGuangzhouGuangdongPeople's Republic of China
| | - Bin Wu
- Department of GastroenterologyThe Third Affiliated Hospital of Sun Yat‐Sen UniversityGuangzhouPeople's Republic of China
- Guangdong Provincial Key Laboratory of Liver Disease ResearchGuangzhouGuangdongPeople's Republic of China
| | - Yidong Yang
- Department of GastroenterologyThe Third Affiliated Hospital of Sun Yat‐Sen UniversityGuangzhouPeople's Republic of China
- Guangdong Provincial Key Laboratory of Liver Disease ResearchGuangzhouGuangdongPeople's Republic of China
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11
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Kim NR, Rho SY, Navarro J, An C, Han DH, Choi JS, Kim MJ, Choi GH. Additional nodules detected using EOB-MRI in patients with resectable single hepatocellular carcinoma: an implication for active treatment strategy. JOURNAL OF LIVER CANCER 2024; 24:92-101. [PMID: 38351675 PMCID: PMC10990668 DOI: 10.17998/jlc.2024.01.25] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Revised: 01/16/2024] [Accepted: 01/25/2024] [Indexed: 04/05/2024]
Abstract
BACKGROUND/AIM Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOBMRI) further enhances the identification of additional hepatic nodules compared with computed tomography (CT) alone; however, the optimal treatment for such additional nodules remains unclear. We investigated the long-term oncological effect of aggressive treatment strategies for additional lesions identified using EOB-MRI in patients with hepatocellular carcinoma (HCC). METHODS Data from 522 patients diagnosed with solitary HCC using CT between January 2008 and December 2012 were retrospectively reviewed. Propensity score-matched (PSM) analysis was used to compare the oncologic outcomes between patients with solitary HCC and those with additional nodules on EOB-MRI after aggressive treatment (resection or radiofrequency ablation [RFA]). RESULTS Among the 383 patients included, 59 had additional nodules identified using EOB-MRI. Compared with patients with solitary HCC, those with additional nodules on EOB-MRI had elevated total bilirubin, aspartate transaminase, and alanine transaminase; had a lower platelet count, higher MELD score, and highly associated with liver cirrhosis (P<0.05). Regarding long-term outcomes, 59 patients with solitary HCC and those with additional nodules after PSM were compared. Disease-free survival (DFS) and overall survival (OS) were comparable between the two groups (DFS, 60.4 vs. 44.3 months, P=0.071; OS, 82.8 vs. 84.8 months, P=0.986). CONCLUSION The aggressive treatment approach, either resection or RFA, for patients with additional nodules identified on EOBMRI was associated with long-term survival comparable with that for solitary HCC. However, further studies are required to confirm these findings.
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Affiliation(s)
- Na Reum Kim
- Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Seoung Yoon Rho
- Department of Surgery, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Korea
| | - Jonathan Navarro
- Division of Surgical Oncology, Department of Surgery, Vicente Sotto Memorial Medical Center, Cebu, Philippines
| | - Chansik An
- Department of Radiology, CHA University Bundang Medical Center, Seongnam, Korea
| | - Dai Hoon Han
- Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Jin Sub Choi
- Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Myeong-Jin Kim
- Department of Radiology, Yonsei University College of Medicine, Seoul, Korea
| | - Gi Hong Choi
- Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
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12
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Ahmad A, Tiwari RK, Siddiqui S, Chadha M, Shukla R, Srivastava V. Emerging trends in gastrointestinal cancers: Targeting developmental pathways in carcinogenesis and tumor progression. INTERNATIONAL REVIEW OF CELL AND MOLECULAR BIOLOGY 2024; 385:41-99. [PMID: 38663962 DOI: 10.1016/bs.ircmb.2023.11.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/25/2024]
Abstract
Gastrointestinal carcinomas are a group of cancers associated with the digestive system and its accessory organs. The most prevalent cancers related to the gastrointestinal tract are colorectal, gall bladder, gastric, hepatocellular, and esophageal cancers, respectively. Molecular aberrations in different signaling pathways, such as signal transduction systems or developmental pathways are the chief triggering mechanisms in different cancers Though a massive advancement in diagnostic and therapeutic interventions results in improved survival of patients with gastrointestinal cancer; the lower malignancy stages of these carcinomas are comparatively asymptomatic. Various gastrointestinal-related cancers are detected at advanced stages, leading to deplorable prognoses and increased rates of recurrence. Recent molecular studies have elucidated the imperative roles of several signaling pathways, namely Wnt, Hedgehog, and Notch signaling pathways, play in the progression, therapeutic responsiveness, and metastasis of gastrointestinal-related cancers. This book chapter gives an interesting update on recent findings on the involvement of developmental signaling pathways their mechanistic insight in gastrointestinalcancer. Subsequently, evidences supporting the exploration of gastrointestinal cancer related molecular mechanisms have also been discussed for developing novel therapeutic strategies against these debilitating carcinomas.
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Affiliation(s)
- Afza Ahmad
- Department of Biosciences, Integral University, Lucknow, Uttar Pradesh, India
| | - Rohit Kumar Tiwari
- Department of Clinical Research, Sharda School of Allied Health Sciences, Sharda University, Greater Noida, Uttar Pradesh, India
| | - Saleha Siddiqui
- Department of Biotechnology, Delhi Technological University, Delhi, India
| | - Muskan Chadha
- Department of Nutrition and Dietetics, Sharda School of Allied Health Sciences, Sharda University, Greater Noida, Uttar Pradesh, India
| | - Ratnakar Shukla
- Department of Clinical Research, Sharda School of Allied Health Sciences, Sharda University, Greater Noida, Uttar Pradesh, India
| | - Vivek Srivastava
- Department of Chemistry & Biochemistry, Sharda School of Basic Sciences & Research, Sharda University, Greater Noida, Uttar Pradesh, India.
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13
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Yen YH, Kuo FY, Eng HL, Liu YW, Yong CC, Li WF, Wang CC, Lin CY. Tumor necrosis as a predictor of early tumor recurrence after resection in patients with hepatoma. PLoS One 2023; 18:e0292144. [PMID: 37972101 PMCID: PMC10653529 DOI: 10.1371/journal.pone.0292144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Accepted: 11/02/2023] [Indexed: 11/19/2023] Open
Abstract
BACKGROUND Tumor necrosis is a significant risk factor affecting patients' prognosis after liver resection (LR) for hepatocellular carcinoma (HCC). We aimed to develop a model with tumor necrosis as a variable to predict early tumor recurrence in HCC patients undergoing LR. MATERIALS AND METHODS Patients who underwent LR between 2010 and 2018 for newly diagnosed HCC but did not receive neoadjuvant therapy were enrolled in this retrospective study. Six predictive factors based on pathological features-tumor size > 5 cm, multiple tumors, high-grade tumor differentiation, tumor necrosis, microvascular invasion, and cirrhosis-were chosen a priori based on clinical relevance to construct a multivariate logistic regression model. The variables were always retained in the model. The impact of each variable on early tumor recurrence within one year of LR was estimated and visualized using a nomogram. The nomogram's performance was evaluated using calibration plots with bootstrapping. RESULTS Early tumor recurrence was observed in 161 (21.3%) patients. The concordance index of the proposed nomogram was 0.722. The calibration plots showed good agreement between nomogram predictions and actual observations of early recurrence. CONCLUSION We developed a nomogram incorporating tumor necrosis to predict early recurrence of HCC after LR. Its predictive accuracy is satisfactory.
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Affiliation(s)
- Yi-Hao Yen
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Fang-Ying Kuo
- Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Hock-Liew Eng
- Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yueh-Wei Liu
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chee-Chien Yong
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Wei-Feng Li
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chih-Chi Wang
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chih-Yun Lin
- Biostatistics Center of Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
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14
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Iijima H, Kudo M, Kubo S, Kurosaki M, Sakamoto M, Shiina S, Tateishi R, Osamu N, Fukumoto T, Matsuyama Y, Murakami T, Takahashi A, Miyata H, Kokudo N. Report of the 23rd nationwide follow-up survey of primary liver cancer in Japan (2014-2015). Hepatol Res 2023; 53:895-959. [PMID: 37574758 DOI: 10.1111/hepr.13953] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 08/01/2023] [Indexed: 08/15/2023]
Abstract
For the 23rd Nationwide Follow-up Survey of Primary Liver Cancer in Japan, data from 20 889 newly registered patients and 42 274 previously registered follow-up patients were compiled from 516 institutions over a 2-year period from January 1, 2014 to December 31, 2015. Basic statistics compiled for patients newly registered in the 23rd survey were cause of death, past medical history, clinical diagnosis, imaging diagnosis, treatment-related factors, pathological diagnosis, recurrence status, and autopsy findings. Compared with the previous 22nd survey, the population of patients with hepatocellular carcinoma (HCC) was older at the time of clinical diagnosis, had more female patients, had more patients with non-B non-C HCC, had smaller tumor diameter, and was more frequently treated with hepatectomy. Cumulative survival rates were calculated for HCC, intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma (combined HCC and intrahepatic cholangiocarcinoma) by treatment type and background characteristics for patients newly registered between 2004 and 2015 whose final outcome was survival or death. The median overall survival and cumulative survival rates for HCC were calculated by dividing patients by combinations of background factors (number of tumors, tumor diameter, Child-Pugh grade, or albumin-bilirubin grade) and by treatment type (hepatectomy, radiofrequency ablation therapy, transcatheter arterial chemoembolization, hepatic arterial infusion chemotherapy, and systemic therapy). The same values were also calculated according to registration date by dividing patients newly registered between 1978 and 2015 into five time period groups. The data obtained from this nationwide follow-up survey are expected to contribute to advancing clinical research and treatment of primary liver cancer in the world.
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Affiliation(s)
- Hiroko Iijima
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Masatoshi Kudo
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan
| | - Shoji Kubo
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Masayuki Kurosaki
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- Department of Gastroenterology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Michiie Sakamoto
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- School of Medicine, International University of Health and Welfare, Tokyo, Japan
| | - Shuichiro Shiina
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Ryosuke Tateishi
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Nakashima Osamu
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- Department of Clinical Laboratory Medicine, Kurume University Hospital, Kurume, Japan
| | - Takumi Fukumoto
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yutaka Matsuyama
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- Department of Biostatistics, School of Public Health, University of Tokyo, Tokyo, Japan
| | - Takamichi Murakami
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- Department of Diagnostic and Interventional Radiology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Arata Takahashi
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- National Clinical Database, Tokyo, Japan
- Department of Healthcare Quality Assessment, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hiroaki Miyata
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- National Clinical Database, Tokyo, Japan
- Department of Healthcare Quality Assessment, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Norihiro Kokudo
- Follow-up Survey Committee, Japan Liver Cancer Association, Osaka, Japan
- National Center for Global Health and Medicine, Tokyo, Japan
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15
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Chavda V, Zajac KK, Gunn JL, Balar P, Khadela A, Vaghela D, Soni S, Ashby CR, Tiwari AK. Ethnic differences in hepatocellular carcinoma prevalence and therapeutic outcomes. Cancer Rep (Hoboken) 2023; 6 Suppl 1:e1821. [PMID: 37344125 PMCID: PMC10440848 DOI: 10.1002/cnr2.1821] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 03/17/2023] [Accepted: 04/10/2023] [Indexed: 06/23/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. The incidence of HCC is affected by genetic and non-genetic factors. Genetically, mutations in the genes, tumor protein P53 (TP53), catenin beta 1 (CTNNB1), AT-rich interaction domain 1A (ARIC1A), cyclin dependent kinase inhibitor 2A (CDKN2A), mannose 6-phosphate (M6P), smooth muscle action against decapentaplegic (SMAD2), retinoblastoma gene (RB1), cyclin D, antigen presenting cells (APC), AXIN1, and E-cadherin, have been shown to contribute to the occurrence of HCC. Non-genetic factors, including alcohol consumption, exposure to aflatoxin, age, gender, presence of hepatitis B (HBV), hepatitis C (HCV), and non-alcoholic fatty liver disease (NAFLD), increase the risk of HCC. RECENT FINDINGS The severity of the disease and its occurrence vary based on geographical location. Furthermore, men and minorities have been shown to be disproportionately affected by HCC, compared with women and non-minorities. Ethnicity has been reported to significantly affect tumorigenesis and clinical outcomes in patients diagnosed with HCC. Generally, differences in gene expression and/or the presence of comorbid medical diseases affect or influence the progression of HCC. Non-Caucasian HCC patients are significantly more likely to have poorer survival outcomes, compared to their Caucasian counterparts. Finally, there are a number of factors that contribute to the success rate of treatments for HCC. CONCLUSION Assessment and treatment of HCC must be consistent using evidence-based guidelines and standardized outcomes, as well as international clinical practice guidelines for global consensus. Standardizing the assessment approach and method will enable comparison and improvement of liver cancer research through collaboration between researchers, healthcare providers, and advocacy groups. In this review, we will focus on discussing epidemiological factors that result in deviations and changes in treatment approaches for HCC.
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Affiliation(s)
- Vivek Chavda
- Department of Pharmaceutics and Pharmaceutical TechnologyL M College of PharmacyAhmedabadIndia
| | - Kelsee K. Zajac
- Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical SciencesUniversity of ToledoOhioUSA
| | - Jenna Lynn Gunn
- Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical SciencesUniversity of ToledoOhioUSA
| | - Pankti Balar
- Pharmacy SectionL M College of PharmacyAhmedabadIndia
| | - Avinash Khadela
- Department of PharmacologyL M College of PharmacyAhmedabadIndia
| | - Dixa Vaghela
- Pharmacy SectionL M College of PharmacyAhmedabadIndia
| | - Shruti Soni
- PharmD SectionL M College of PharmacyAhmedabadIndia
| | - Charles R. Ashby
- Department of Pharmaceutical Sciences, College of PharmacySt. John's UniversityNew YorkNew YorkUSA
| | - Amit K. Tiwari
- Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical SciencesUniversity of ToledoOhioUSA
- Department of Cancer Biology, College of Medicine and Life SciencesUniversity of ToledoToledoOhioUSA
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16
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Yu X, Lei X. Application of the Multi-Omics Liquid Biopsy Method M2P-HCC in Early Liver Cancer Screening for High-Risk Individuals with Hepatitis B-Related Liver Cancer. Diagnostics (Basel) 2023; 13:2484. [PMID: 37568847 PMCID: PMC10417463 DOI: 10.3390/diagnostics13152484] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 07/13/2023] [Accepted: 07/21/2023] [Indexed: 08/13/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, with low rates of early diagnosis and surgical resection. In recent years, with the rapid development of liquid biopsy technology, circulating tumor DNA (ctDNA) has emerged as a research hotspot in the field of precision medicine for liver cancer. Existing studies have demonstrated the suitability of ctDNA for combined detection with other liver cancer diagnostic markers, enabling a multi-index analysis. In recent years, a novel prediction model has been developed for early liver cancer screening based on ctDNA liquid biopsy, M2P-HCC (methylation, mutation, and protein-HCC), mainly incorporating methylation changes, gene mutations, and protein markers associated with liver cancer. Preliminary validation in the HCCscreenTM Investigational (HIT, ChiCTR1800020233) study, which focused on screening early liver cancer in communities with Hepatitis B surface antigen (HBsAg) positivity, yielded promising results with 100% sensitivity and 94% specificity. However, it remains uncertain whether M2P-HCC can be effectively applied in high-risk populations for Hepatitis B-associated liver cancer, warranting further research. METHODS Patients who were under long-term follow-up at the outpatient clinic of the Infectious Diseases Center of West China Hospital of Sichuan University from December 2020 to January 2023 were recruited in this prospective observational study and underwent the M2P-HCC test. The study population consisted of high-risk patients with Hepatitis B-related liver cancer who met the inclusion criteria. Patients with a history of previous malignancy, recent blood transfusion, autoimmune diseases, and human immunodeficiency virus (HIV) infection were excluded. Clinical data were collected at a baseline, and all patients underwent the M2P-HCC blood test. Based on the test results, they were categorized into positive, early-warning, and negative groups. Prospective cohort observation and regular follow-ups were performed for 6-8 months. RESULTS 313 patients met the inclusion criteria and were included in the study. After 6-8 months of follow-up, HCC occurred in 41(13.1%) participants. The M2P-HCC test demonstrated good predictive performance with an area under the curve (AUC) of 0.88 (95% CI: 0.81-0.95, p < 0.001) and a cutoff value of 83 points (sensitivity 82.9% and specificity 85.7%). In contrast, the combination of alpha-fetoprotein (AFP) and ultrasound (US) yielded an inferior predictive performance (AUC 0.76 (95% CI: 0.69-0.84, p < 0.001), sensitivity 58.5%, and specificity 94.1%). Multivariate analyses revealed that M2P-HCC was an independent predictor of increased risk of HCC (OR = 1.16 [1.09-1.22], p < 0.001). CONCLUSIONS M2P-HCC liquid biopsy demonstrated good performance for early liver cancer screening in high-risk populations of Hepatitis B-related liver cancer, exhibiting better sensitivity than the combination of AFP and US.
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Affiliation(s)
| | - Xuezhong Lei
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, China;
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17
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Kudo M. Surveillance, Diagnosis, and Treatment Outcome of Hepatocellular Carcinoma in Japan: 2023 Update. Liver Cancer 2023; 12:95-102. [PMID: 37325491 PMCID: PMC10267513 DOI: 10.1159/000530079] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Accepted: 03/06/2023] [Indexed: 06/17/2023] Open
Affiliation(s)
- Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
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18
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Soin A, Lesurtel M, Bhangui P, Cocchi L, Bouattour M, Clavien PA. Are patients with hepatocellular carcinoma and portal vein tumour thrombosis candidates for liver transplantation? J Hepatol 2023; 78:1124-1129. [PMID: 37208099 DOI: 10.1016/j.jhep.2023.03.032] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 03/27/2023] [Indexed: 05/21/2023]
Abstract
In this debate, the authors consider whether patients with hepatocellular carcinoma (HCC) and portal vein tumour thrombosis are candidates for liver transplantation (LT). The argument for LT in this context is based on the premise that, following successful downstaging treatment, LT confers a much greater clinical benefit in terms of survival outcomes than the available alternative (palliative systemic therapy). A major argument against relates to limitations in the quality of evidence for LT in this setting - in relation to study design, as well as heterogeneity in patient characteristics and downstaging protocols. While acknowledging the superior outcomes offered by LT for patients with portal vein tumour thrombosis, the counterargument is that expected survival in such patients is still below accepted thresholds for LT and, indeed, the levels achieved for other patients who receive transplants beyond the Milan criteria. Based on the available evidence, it seems too early for consensus guidelines to recommend such an approach, however, it is hoped that with higher quality evidence and standardised downstaging protocols, LT may soon be more widely indicated, including for this population with high unmet clinical need.
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Affiliation(s)
- Arvinder Soin
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Gurgaon, India
| | - Mickaël Lesurtel
- Department of HPB Surgery & Liver Transplantation, APHP Beaujon Hospital, University of Paris Cité, 100, bd General Leclerc, 92110 Clichy, France
| | - Prashant Bhangui
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Gurgaon, India
| | - Lorenzo Cocchi
- Department of HPB Surgery & Liver Transplantation, APHP Beaujon Hospital, University of Paris Cité, 100, bd General Leclerc, 92110 Clichy, France
| | - Mohamed Bouattour
- Department of Hepatology, APHP Beaujon Hospital, University of Paris Cité, 100, Bd General Leclerc, 92110 Clichy, France
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19
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Bogdanovic A, Djokic Kovac J, Zdujic P, Djindjic U, Dugalic V. Liver resection versus transarterial chemoembolisation for the treatment of intermediate hepatocellular carcinoma: a systematic review and meta-analysis. Int J Surg 2023; 109:1439-1446. [PMID: 37222718 PMCID: PMC10389385 DOI: 10.1097/js9.0000000000000344] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 03/09/2023] [Indexed: 05/25/2023]
Abstract
BACKGROUND Transarterial chemoembolisation (TACE) is the primary treatment for intermediate-stage hepatocellular carcinoma (HCC), according to the updated Barcelona Clinic Liver Cancer (BCLC) staging system. Although growing evidence favours liver resection (LR) over TACE for intermediate-stage HCC, the best treatment option remains controversial. This meta-analysis aimed to compare the overall survival (OS) after LR versus TACE for intermediate-stage HCC. METHODS A comprehensive literature review of PubMed, Embase, Cochrane Library, and Web of Science was performed. Studies that compared the efficacy of LR and TACE in patients with intermediate (BCLC stage B) HCC were selected. According to the recent updated BCLC classification, intermediate stage of HCC was defined as follows: (a) four or more HCC nodules of any size, or (b) two or three nodules, but if at least one tumour is larger than 3 cm. The main outcome was OS, expressed as the hazard ratio. RESULTS Nine eligible studies of 3355 patients were included in the review. The OS of patients who underwent LR was significantly longer than that of patients who underwent TACE (hazard ratio=0.52; 95% CI: 0.39-0.69; I2=79%). Prolonged survival following LR was confirmed after sensitivity analysis of five studies using propensity score matching (HR=0.45; 95% CI: 0.34-0.59; I2=55%). CONCLUSION Patients with intermediate-stage HCC who underwent LR had a longer OS that those who underwent TACE. The role of LR in patients with BCLC stage B should be clarified in future randomised controlled trials.
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Affiliation(s)
- Aleksandar Bogdanovic
- Clinic for Digestive Surgery
- School of Medicine, University of Belgrade, Belgrade, Serbia
| | - Jelena Djokic Kovac
- Center for Radiology and Magnetic Resonance Imaging, University Clinical Center of Serbia
- School of Medicine, University of Belgrade, Belgrade, Serbia
| | | | | | - Vladimir Dugalic
- Clinic for Digestive Surgery
- School of Medicine, University of Belgrade, Belgrade, Serbia
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20
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Devarbhavi H, Asrani SK, Arab JP, Nartey YA, Pose E, Kamath PS. Global burden of Liver Disease: 2023 Update. J Hepatol 2023:S0168-8278(23)00194-0. [PMID: 36990226 DOI: 10.1016/j.jhep.2023.03.017] [Citation(s) in RCA: 690] [Impact Index Per Article: 345.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 03/06/2023] [Accepted: 03/09/2023] [Indexed: 03/31/2023]
Abstract
Liver disease accounts for 2 million deaths and is responsible for 4% of all deaths (1 out of every 25 deaths worldwide); approximately 2/3 of all liver related deaths occur in men. Deaths are largely attributable to complications of cirrhosis and hepatocellular carcinoma, with acute hepatitis accounting for a smaller proportion of deaths. The most common causes of cirrhosis worldwide are related to viral hepatitis, alcohol, and nonalcoholic fatty liver disease (NAFLD). Hepatotropic viruses are the etiological factor in most cases of acute hepatitis, but drug-induced liver injury increasingly accounts for a significant proportion of cases. This iteration of the global burden of liver disease is an update of the 2019 version and focuses mainly on areas where significant new information is available like alcohol-associated liver disease, NAFLD, viral hepatitis, and HCC. We also devote a separate section to the burden of liver disease in Africa, an area of the world typically neglected in such documents.
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Affiliation(s)
- Harshad Devarbhavi
- Department of Gastroenterology and Hepatology, St. John's Medical College Hospital, Bangalore, India
| | - Sumeet K Asrani
- Baylor University Medical Center, Baylor Scott and White, Dallas, TX, United States.
| | - Juan Pablo Arab
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University & London Health Sciences Centre, London, Ontario, Canada; Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile
| | - Yvonne Ayerki Nartey
- Department of Internal Medicine, School of Medical Sciences, University of Cape Coast, Cape Coast, Ghana
| | - Elisa Pose
- Liver Unit, Hospital Clinic of Barcelona. Institut D'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
| | - Patrick S Kamath
- Mayo Clinic College of Medicine and Science, Rochester, MN, United States
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21
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Sempokuya T, Warner J, Azawi M, Nogimura A, Wong LL. Current status of disparity in liver disease. World J Hepatol 2022; 14:1940-1952. [PMID: 36483604 PMCID: PMC9724102 DOI: 10.4254/wjh.v14.i11.1940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Revised: 11/09/2022] [Accepted: 11/16/2022] [Indexed: 11/24/2022] Open
Abstract
Disparities have emerged as an important issue in many aspects of healthcare in developed countries and may be based on race, ethnicity, sex, geographical location, and socioeconomic status. For liver disease specifically, these potential disparities can affect access to care and outcome in viral hepatitis, chronic liver disease, and hepatocellular carcinoma. Shortages in hepatologists and medical providers versed in liver disease may amplify these disparities by compromising early detection of liver disease, surveillance for hepatocellular carcinoma, and prompt referral to subspecialists and transplant centers. In the United States, continued efforts have been made to address some of these disparities with better education of healthcare providers, use of telehealth to enhance access to specialists, reminders in electronic medical records, and modifying organ allocation systems for liver transplantation. This review will detail the current status of disparities in liver disease and describe current efforts to minimize these disparities.
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Affiliation(s)
- Tomoki Sempokuya
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, United States
| | - Josh Warner
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, United States
| | - Muaataz Azawi
- Division of Gastroenterology and Hepatology, Sanford Center for Digestive Health, Sioux Falls 57105, SD, Uruguay
| | - Akane Nogimura
- Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Aichi, Japan
- Division of Psychiatry and Cognitive-Behavioral Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Aichi, Japan
| | - Linda L Wong
- Department of Surgery, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96813, United States
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22
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Jang TY, Dai CY. Cutoff values of protein induced by vitamin K absence or antagonist II for diagnosing hepatocellular carcinoma. Medicine (Baltimore) 2022; 101:e30936. [PMID: 36181046 PMCID: PMC9524990 DOI: 10.1097/md.0000000000030936] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Protein induced by vitamin K absence or antagonist II (PIVKA-II) is a promising serum marker for hepatocellular carcinoma (HCC). There are limited data on its cutoff value in HCC for Taiwanese cirrhosis patients. This study aimed to investigate the diagnostic value of PIVKA-II levels in patients with suspected HCC. In total, 88 patients with chronic hepatitis and suspected HCC by ultrasound, elevated α-fetoprotein (AFP) or PIVKA-II levels were consecutively enrolled. Their baseline characteristics and findings on dynamic phases of computed tomography (CT) or magnetic resonance imaging (MRI) were examined. Sixty participants had cirrhosis and 34 had HCC. The median levels of PIVKA-II in non-cirrhosis and cirrhosis patients without or with HCC were 28.0, 48.0, and 847.0 mAU/mL, respectively. The optimal cutoff value of PIVKA-II in predicting HCC was 78.0 mAU/mL. Combining AFP with PIVKAII mildly increased its diagnostic performance for HCC, yielding higher specificity and positive predictive value. Significant factors predicting HCC in multivariate regression analysis were PIVKA >78.0 mAU/mL and fatty liver. Monitoring PIVKA-II level is suitable for noninvasively assessing HCC in patients with chronic hepatitis, particularly with AFP.
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Affiliation(s)
- Tyng-Yuan Jang
- PhD Program of Environmental and Occupational Medicine and Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Pingtung Hospital, Ministry of Health and Welfare, Ping-Tung, Taiwan
| | - Chia-Yen Dai
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Occupational and Environmental Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- *Correspondence: Chia-Yen Dai, Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, 100 Tzyou Road, Kaohsiung City 807, Taiwan (e-mail: )
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23
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Liang Y, Guo GL, Zhang L. Current and Emerging Molecular Markers of Liver Diseases: A Pathogenic Perspective. Gene Expr 2022; 21:9-19. [PMID: 38911667 PMCID: PMC11192043 DOI: 10.14218/gejlr.2022.00010] [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] [Indexed: 11/11/2022]
Abstract
In the past decade, with the rapid development of molecular medicine and the application of more sophisticated methods for disease diagnosis and treatment, a number of molecular markers have become available for liver diseases. Pathogenesis-related markers are likely to be effectively discovered and rigorously validated, due to the unique biological links to diseases. The present study reviews the predominant clinical and research articles in the previous decade to provide a pathogenic perspective of current and emerging biomarkers for liver diseases, including hepatocellular neoplasms (e.g. hepatocellular carcinoma), non-neoplastic hepatocellular diseases, intrahepatic biliary diseases, and other liver diseases. Although it remains challenging to cover all markers for the diagnosis and prognosis of liver diseases, current and emerging molecular markers in clinical practice and under investigation are reviewed in a wide spectrum of liver diseases, in order to help clinicians and researchers identify liver disease markers for reference.
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Affiliation(s)
- Yuanxin Liang
- Department of Pathology, Yale University, New Haven, Connecticut, USA
| | - Grace L Guo
- Department of Pharmacology and Toxicology, Ernst Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, USA
- Research and Development Service, Veterans Health Administration, New Jersey Health Care System, East Orange, New Jersey, USA
| | - Lanjing Zhang
- Department of Pathology, Princeton Medical Center, Plainsboro, New Jersey, USA
- Department of Chemical Biology, Ernst Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, USA
- Department of Biological Sciences, Rutgers University, Newark, New Jersey, USA
- Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA
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24
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Liu Y, Liu L. Changes in the Epidemiology of Hepatocellular Carcinoma in Asia. Cancers (Basel) 2022; 14:cancers14184473. [PMID: 36139633 PMCID: PMC9496757 DOI: 10.3390/cancers14184473] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Revised: 09/09/2022] [Accepted: 09/13/2022] [Indexed: 11/23/2022] Open
Abstract
Simple Summary The incidence and mortality of hepatocellular carcinoma (HCC) in Asia are among the world leaders. By understanding the changes in prevalence and influencing factors of HCC, we can better understand the current situation in Asia and take measures to reduce the incidence. Abstract Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, with high morbidity and mortality, and the incidence is on the rise. HCC imposes a heavy healthcare burden on Asian countries due to the presence of multiple HCC risk factors in this area. Chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, non-alcoholic liver disease (NAFLD), aflatoxin and alcohol intake are the causes of HCC that cannot be ignored. Compared with the pre-vaccination era, universal vaccination of newborns reduces the incidence of HCC. Anti-viral therapy with nucleos(t)ide analogues also causes a decline in HCC incidence. Early screening and direct-acting antiviral agent are beneficial to the prevention and treatment of HCV. For HCC caused by NAFLD and other reasons, lifestyle changes are imperative. This paper introduces the epidemiological trends of HCC in Asia and highlight future efforts. Focusing on prevention may be the most effective way to improve the prognosis of this hard-to-treat cancer.
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Affiliation(s)
- Yao Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China
- Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Hefei 230001, China
- Anhui Provincial Clinical Research Center for Hepatobiliary Diseases, Hefei 230001, China
| | - Lianxin Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China
- Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Hefei 230001, China
- Anhui Provincial Clinical Research Center for Hepatobiliary Diseases, Hefei 230001, China
- Correspondence:
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Feng MY, Chan LL, Chan SL. Drug Treatment for Advanced Hepatocellular Carcinoma: First-Line and Beyond. Curr Oncol 2022; 29:5489-5507. [PMID: 36005172 PMCID: PMC9406660 DOI: 10.3390/curroncol29080434] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 07/29/2022] [Accepted: 08/02/2022] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) has high mortality. The option of systemic therapy has increased significantly over the past five years. Sorafenib was the first multikinase inhibitor, introduced in 2007, as a treatment option for HCC, and it was the only effective systemic treatment for more than ten years. It was not until 2017 that several breakthroughs were made in the development of systemic strategies. Lenvatinib, another multikinase inhibitor, stood out successfully after sorafenib, and has been applied to clinical use in the first-line setting. Other multikinase inhibitors such as regorafenib, ramucirumab and cabozantinib, were approved in quick succession as second-line therapies. Concurrently, immune checkpoint inhibitors (ICIs) have readily become established treatments for many solid tumors, including HCC. The most studied ICIs to date, target programmed cell death-1 (PD-1), its ligand PD-L1, and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). These ICIs have demonstrated efficacy in treating advanced HCC. More recently, combination of bevacizumab and atezolizumab (ICI targeting PD-L1) was approved as the gold-standard first-line therapy. Combination of ICIs with nivolumab and ipilimumab was also approved in the second-line setting for those who failed sorafenib. At the moment, numerous clinical trials in advanced HCC are underway, which will bring continuous change to the management, and increase the survival, for patients with advanced HCC. Our review article: (1) summarizes United States Food and Drug Administration (US FDA) approved systemic therapies in advanced HCC, (2) reports the evidence of currently approved treatments, (3) discusses potential drugs/drug combinations being currently tested in phase III clinical trials, and (4) proposes possible future directions in drug development for advanced HCC.
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Affiliation(s)
- Maple Ye Feng
- Department of Clinical Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
| | - Landon L. Chan
- Department of Oncology, Princess Margaret Hospital, Hong Kong, China
| | - Stephen Lam Chan
- Department of Clinical Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
- State Key Laboratory of Translational Oncology, Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong, China
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Ghamari S, Yoosefi M, Abbasi‐Kangevari M, Malekpour M, Saeedi Moghaddam S, Shahin S, Esfahani Z, Koolaji S, Shobeiri P, Ghaffari A, Sohrabi H, Kazemi A, Rezaei N, Larijani B, Farzadfar F. Trends in Global, Regional, and National Burden and Quality of Care Index for Liver Cancer by Cause from Global Burden of Disease 1990-2019. Hepatol Commun 2022; 6:1764-1775. [PMID: 35134275 PMCID: PMC9234674 DOI: 10.1002/hep4.1910] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Despite the tremendous burden of liver cancer and its underlying causes on humankind, there appear to be heterogeneities in coping approaches. The objective of this study was to compare the burden and the quality-of-care of liver cancer by causes among different countries and regions in both sexes and various age groups 1990-2019. Data of liver cancer and underlying causes, including hepatitis B virus (HBV), hepatitis C virus (HCV), alcohol use, nonalcoholic steatohepatitis (NASH), and other causes were obtained from the Global Burden of Diseases 2019. Incidence, prevalence, death, and disability-adjusted life-years (DALYs) were assessed. Principal component analysis was used to combine age-standardized mortality-to-incidence ratio, DALY-to-prevalence ratio, prevalence-to-incidence ratio, and years of life lost-to-years lived with disability into a single proxy named Quality of Care Index (QCI). Globally, the age-standardized incidence, DALYs, and death rates decreased from 1990 to 2019, while the QCI scores increased by 68.5%. The QCI score of liver cancer was from as high as 83.3 in high Sociodemographic Index (SDI) countries to values as low as 26.4 in low SDI countries in 2019. Japan had the highest QCI score (QCI = 100). The age-standardized death rates of liver cancer due to all underlying causes were decreasing during the past 30 years, with the most decrease for HBV. Consistently, the global QCI scores of liver cancer due to HBV, HCV, alcohol use, NASH, and other causes reached 53.5, 61.8, 54.3, 52.9, and 63.7, respectively, in 2019. Conclusion: Although the trends in burden are decreasing and the QCI improved from 1990 to 2019 globally, there is a wide gap between countries. Given the inequities in health care quality, there is an urgent need to address discrimination and bridge the gap.
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Affiliation(s)
- Seyyed‐Hadi Ghamari
- Non‐communicable Diseases Research CenterEndocrinology and Metabolism Population Sciences InstituteTehran University of Medical SciencesTehranIran
| | - Moein Yoosefi
- Non‐communicable Diseases Research CenterEndocrinology and Metabolism Population Sciences InstituteTehran University of Medical SciencesTehranIran
| | - Mohsen Abbasi‐Kangevari
- Non‐communicable Diseases Research CenterEndocrinology and Metabolism Population Sciences InstituteTehran University of Medical SciencesTehranIran
| | - Mohammad‐Reza Malekpour
- Non‐communicable Diseases Research CenterEndocrinology and Metabolism Population Sciences InstituteTehran University of Medical SciencesTehranIran
| | - Sahar Saeedi Moghaddam
- Non‐communicable Diseases Research CenterEndocrinology and Metabolism Population Sciences InstituteTehran University of Medical SciencesTehranIran
| | - Sarvenaz Shahin
- Non‐communicable Diseases Research CenterEndocrinology and Metabolism Population Sciences InstituteTehran University of Medical SciencesTehranIran
| | - Zahra Esfahani
- Non‐communicable Diseases Research CenterEndocrinology and Metabolism Population Sciences InstituteTehran University of Medical SciencesTehranIran
- Department of BiostatisticsUniversity of Social Welfare and Rehabilitation SciencesTehranIran
| | - Sogol Koolaji
- Non‐communicable Diseases Research CenterEndocrinology and Metabolism Population Sciences InstituteTehran University of Medical SciencesTehranIran
| | - Parnian Shobeiri
- Non‐communicable Diseases Research CenterEndocrinology and Metabolism Population Sciences InstituteTehran University of Medical SciencesTehranIran
| | - Aydin Ghaffari
- Non‐communicable Diseases Research CenterEndocrinology and Metabolism Population Sciences InstituteTehran University of Medical SciencesTehranIran
| | - Hanye Sohrabi
- Non‐communicable Diseases Research CenterEndocrinology and Metabolism Population Sciences InstituteTehran University of Medical SciencesTehranIran
| | - Ameneh Kazemi
- Non‐communicable Diseases Research CenterEndocrinology and Metabolism Population Sciences InstituteTehran University of Medical SciencesTehranIran
| | - Negar Rezaei
- Non‐communicable Diseases Research CenterEndocrinology and Metabolism Population Sciences InstituteTehran University of Medical SciencesTehranIran
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences InstituteTehran University of Medical SciencesTehranIran
| | - Bagher Larijani
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences InstituteTehran University of Medical SciencesTehranIran
| | - Farshad Farzadfar
- Non‐communicable Diseases Research CenterEndocrinology and Metabolism Population Sciences InstituteTehran University of Medical SciencesTehranIran
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences InstituteTehran University of Medical SciencesTehranIran
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27
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Wang Z, Liu M, Zhang DZ, Wu SS, Hong ZX, He GB, Yang H, Xiang BD, Li X, Jiang TA, Li K, Tang Z, Huang F, Lu M, Chen JA, Lin YC, Lu X, Wu YQ, Zhang XW, Zhang YF, Cheng C, Ye HL, Wang LT, Zhong HG, Zhong JH, Wang L, Chen M, Liang FF, Chen Y, Xu YS, Yu XL, Cheng ZG, Liu FY, Han ZY, Tang WZ, Yu J, Liang P. Microwave ablation versus laparoscopic resection as first-line therapy for solitary 3-5-cm HCC. Hepatology 2022; 76:66-77. [PMID: 35007334 DOI: 10.1002/hep.32323] [Citation(s) in RCA: 55] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Revised: 12/22/2021] [Accepted: 12/22/2021] [Indexed: 01/27/2023]
Abstract
BACKGROUND AND AIMS The study objective was to compare the effectiveness of microwave ablation (MWA) and laparoscopic liver resection (LLR) on solitary 3-5-cm HCC over time. APPROACH AND RESULTS From 2008 to 2019, 1289 patients from 12 hospitals were enrolled in this retrospective study. Diagnosis of all lesions were based on histopathology. Propensity score matching was used to balance all baseline variables between the two groups in 2008-2019 (n = 335 in each group) and 2014-2019 (n = 257 in each group) cohorts, respectively. For cohort 2008-2019, during a median follow-up of 35.8 months, there were no differences in overall survival (OS) between MWA and LLR (HR: 0.88, 95% CI 0.65-1.19, p = 0.420), and MWA was inferior to LLR regarding disease-free survival (DFS) (HR 1.36, 95% CI 1.05-1.75, p = 0.017). For cohort 2014-2019, there was comparable OS (HR 0.85, 95% CI 0.56-1.30, p = 0.460) and approached statistical significance for DFS (HR 1.33, 95% CI 0.98-1.82, p = 0.071) between MWA and LLR. Subgroup analyses showed comparable OS in 3.1-4.0-cm HCCs (HR 0.88, 95% CI 0.53-1.47, p = 0.630) and 4.1-5.0-cm HCCs (HR 0.77, 95% CI 0.37-1.60, p = 0.483) between two modalities. For both cohorts, MWA shared comparable major complications (both p > 0.05), shorter hospitalization, and lower cost to LLR (all p < 0.001). CONCLUSIONS MWA might be a first-line alternative to LLR for solitary 3-5-cm HCC in selected patients with technical advances, especially for patients unsuitable for LLR.
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Affiliation(s)
- Zhen Wang
- Department of Interventional Ultrasound, PLA Medical College & Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
- Guangxi Clinical Research Center for CRC, Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Miao Liu
- Graduate School of Chinese PLA General Hospital, Beijing, China
| | - De-Zhi Zhang
- Abdominal Ultrasound Department, the First Hospital of Jilin University, Changchun, China
| | - Song-Song Wu
- Department of Ultrasonography, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
| | - Zhi-Xian Hong
- Department of Hepatobiliary Surgery, PLA Medical College & Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Guang-Bin He
- Department of Ultrasound, Xijing Hospital, the Fourth Military Medical University, Xian, China
| | - Hong Yang
- Department of Ultrasound, the First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Bang-de Xiang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Xiao Li
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Tian-An Jiang
- Department of Ultrasound Medicine, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Kai Li
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zhe Tang
- Department of Surgery, the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, P. R. China
| | - Fei Huang
- Department of General Surgery, the Second Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Man Lu
- Ultrasound Medical Center, Sichuan Cancer Hospital Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Ji-An Chen
- Department of General Surgery, the Second Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Yu-Cheng Lin
- Department of Ultrasonography, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
| | - Xiao Lu
- Department of Ultrasound, Xijing Hospital, the Fourth Military Medical University, Xian, China
| | - Yu-Quan Wu
- Department of Ultrasound, the First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Xiao-Wu Zhang
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ye-Fan Zhang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Chao Cheng
- Department of Ultrasound Medicine, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Huo-Lin Ye
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Lan-Tian Wang
- Department of Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P. R. China
| | - Hua-Ge Zhong
- Guangxi Clinical Research Center for CRC, Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Jian-Hong Zhong
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Lu Wang
- Ultrasound Medical Center, Sichuan Cancer Hospital Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Miao Chen
- Department of Radiology, Guangxi Medical University Cancer Hospital, Guangxi Medical University, Nanning, P. R. China
| | - Fang-Fang Liang
- Department of Medical Oncology, the First Affiliated Hospital of Guangxi Medical University, Nanning, P. R. China
| | - Yi Chen
- Guangxi Clinical Research Center for CRC, Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Yan-Song Xu
- Department of Emergency, the First Affiliated Hospital of Guangxi Medical University, Nanning, P. R. China
| | - Xiao-Ling Yu
- Department of Interventional Ultrasound, PLA Medical College & Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Zhi-Gang Cheng
- Department of Interventional Ultrasound, PLA Medical College & Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Fang-Yi Liu
- Department of Interventional Ultrasound, PLA Medical College & Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Zhi-Yu Han
- Department of Interventional Ultrasound, PLA Medical College & Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Wei-Zhong Tang
- Guangxi Clinical Research Center for CRC, Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Jie Yu
- Department of Interventional Ultrasound, PLA Medical College & Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Ping Liang
- Department of Interventional Ultrasound, PLA Medical College & Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
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Burra P, Bretthauer M, Buti Ferret M, Dugic A, Fracasso P, Leja M, Matysiak Budnik T, Michl P, Ricciardiello L, Seufferlein T, van Leerdam M, Botos A. Digestive cancer screening across Europe. United European Gastroenterol J 2022; 10:435-437. [PMID: 35474447 PMCID: PMC9103365 DOI: 10.1002/ueg2.12230] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Affiliation(s)
- Patrizia Burra
- Department of Surgery, Oncology and GastroenterologyMultivisceral Transplant UnitPadua University HospitalPaduaItaly
| | - Michael Bretthauer
- Department of Health Management and Health EconomyInstitute of Health and SocietyUniversity of OsloOsloNorway
| | | | - Ana Dugic
- Department of GastroenterologyKlinikum Bayreuth Friedrich‐Alexander‐University Erlangen‐NürnbergBayreuthGermany
| | | | - Marcis Leja
- Institute of Clinical and Preventive MedicineUniversity of Latvia and Riga East University HospitalRigaLatvia
| | - Tamara Matysiak Budnik
- Institut des maladies de l'appareil digestifCentre Hospitalier Universitaire de NantesNantesFrance
| | - Patrick Michl
- Department of Internal Medicine IMartin‐Luther University Halle‐WittenbergHalleGermany
| | - Luigi Ricciardiello
- Department of Medical and Surgical SciencesUniversita degli Studi di BolognaBolognaItaly
| | | | | | - Andreea Botos
- United European Gastroenterology (UEG)AustriaAustria
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29
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Wu M, Shi QM, Duan SL, Ou-yang DJ, Chen P, Tu B, Huang P. Insights into the Association Between QSER1 and M2 Macrophages and Remarkable Malignancy Characteristics in Hepatocellular Carcinoma. Int J Gen Med 2022; 15:1765-1775. [PMID: 35210841 PMCID: PMC8863346 DOI: 10.2147/ijgm.s352574] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 02/08/2022] [Indexed: 11/23/2022] Open
Abstract
Purpose Glutamine and serine rich 1 (QSER1), as a DNA methylation modulator, play a crucial role in transforming tumor cells. Previous studies have shown that QSER1 plays a role in regulating the progression of various malignancies and that QSER1 dysfunction is connected with precancerous lesions of hepatocellular carcinoma (HCC) as well as HCC prognosis. However, little is known about the detailed contribution of QSER1 in HCC. Patients and Methods Various statistical methods such as Kaplan–Meier method, AUC analysis, GSEA, and immune-infiltration analysis were used to evaluate the relationship between QSER1 expression and clinical features, prognostic factors, and potential functional mechanisms of QSER1. Results QSER1 expression was negatively correlated with clinicopathological features (clinical stage, pathological grade, TP53 mutation, lymph node metastasis) and clinical outcome (overall survival versus recurrence). Functional enrichment analysis further suggested that QSER1 is involved in multiple pathways related to DNA replication and tumor immunity. TIMER analysis indicated that high QSER1 expression was significantly associated with higher macrophage infiltration and poorer macrophage-related outcomes. In particular, QSER1 was significantly more associated with M2 macrophages than M1 macrophages. Conclusion Overall, elevated QSER1 is a potential prognostic marker for HCC and is associated with immune infiltration in HCC.
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Affiliation(s)
- Min Wu
- Department of General Surgery, Xiangya Hospital Central South University, Changsha, Hunan, 410008, People’s Republic of China
| | - Qi-man Shi
- Department of General Surgery, Xiangya Hospital Central South University, Changsha, Hunan, 410008, People’s Republic of China
| | - Sai-Li Duan
- Department of General Surgery, Xiangya Hospital Central South University, Changsha, Hunan, 410008, People’s Republic of China
| | - Deng-jie Ou-yang
- Department of General Surgery, Xiangya Hospital Central South University, Changsha, Hunan, 410008, People’s Republic of China
| | - Pei Chen
- Department of General Surgery, Xiangya Hospital Central South University, Changsha, Hunan, 410008, People’s Republic of China
| | - Biao Tu
- Department of General Surgery, Xiangya Hospital Central South University, Changsha, Hunan, 410008, People’s Republic of China
| | - Peng Huang
- Department of General Surgery, Xiangya Hospital Central South University, Changsha, Hunan, 410008, People’s Republic of China
- Correspondence: Peng Huang, Email
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El-Nakeep S. Molecular and genetic markers in hepatocellular carcinoma: In silico analysis to clinical validation (current limitations and future promises). World J Gastrointest Pathophysiol 2022; 13:1-14. [PMID: 35116176 PMCID: PMC8788164 DOI: 10.4291/wjgp.v13.i1.1] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Revised: 05/15/2021] [Accepted: 12/22/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the second cause of cancer-related mortality. The diagnosis of HCC depends mainly on -fetoprotein, which is limited in its diagnostic and screening capabilities. There is an urgent need for a biomarker that detects early HCC to give the patients a chance for curative treatment. New targets of therapy could enhance survival and create future alternative curative methods. In silico analysis provides both; discovery of biomarkers, and understanding of the molecular pathways, to pave the way for treatment development. This review discusses the role of in silico analysis in the discovery of biomarkers, molecular pathways, and the role the author has contributed to this area of research. It also discusses future aspirations and current limitations. A literature review was conducted on the topic using various databases (PubMed, Science Direct, and Wiley Online Library), searching in various reviews, and editorials on the topic, with overviewing the author's own published and unpublished work. This review discussed the steps of the validation process from in silico analysis to in vivo validation, to incorporation into clinical practice guidelines. In addition, reviewing the recent lines of research of bioinformatic studies related to HCC. In conclusion, the genetic, molecular and epigenetic markers discoveries are hot areas for HCC research. Bioinformatics will enhance our ability to accomplish this understanding in the near future. We face certain limitations that we need to overcome.
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Affiliation(s)
- Sarah El-Nakeep
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo 11591, Egypt
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Karlsen TH, Sheron N, Zelber-Sagi S, Carrieri P, Dusheiko G, Bugianesi E, Pryke R, Hutchinson SJ, Sangro B, Martin NK, Cecchini M, Dirac MA, Belloni A, Serra-Burriel M, Ponsioen CY, Sheena B, Lerouge A, Devaux M, Scott N, Hellard M, Verkade HJ, Sturm E, Marchesini G, Yki-Järvinen H, Byrne CD, Targher G, Tur-Sinai A, Barrett D, Ninburg M, Reic T, Taylor A, Rhodes T, Treloar C, Petersen C, Schramm C, Flisiak R, Simonova MY, Pares A, Johnson P, Cucchetti A, Graupera I, Lionis C, Pose E, Fabrellas N, Ma AT, Mendive JM, Mazzaferro V, Rutter H, Cortez-Pinto H, Kelly D, Burton R, Lazarus JV, Ginès P, Buti M, Newsome PN, Burra P, Manns MP. The EASL-Lancet Liver Commission: protecting the next generation of Europeans against liver disease complications and premature mortality. Lancet 2022; 399:61-116. [PMID: 34863359 DOI: 10.1016/s0140-6736(21)01701-3] [Citation(s) in RCA: 351] [Impact Index Per Article: 117.0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Revised: 07/10/2021] [Accepted: 07/15/2021] [Indexed: 02/07/2023]
Affiliation(s)
- Tom H Karlsen
- Department of Transplantation Medicine and Research Institute for Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet and University of Oslo, Oslo, Norway.
| | - Nick Sheron
- Institute of Hepatology, Foundation for Liver Research, Kings College London, London, UK
| | - Shira Zelber-Sagi
- School of Public Health, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel; Department of Gastroenterology, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Patrizia Carrieri
- Aix-Marseille University, Inserm, Institut de recherche pour le développement, Sciences Economiques et Sociales de la Santé et Traitement de l'Information Médicale (SESSTIM), ISSPAM, Marseille, France
| | - Geoffrey Dusheiko
- School of Medicine, University College London, London, UK; Kings College Hospital, London, UK
| | - Elisabetta Bugianesi
- Department of Medical Sciences, Division of Gastroenterology, University of Torino, Torino, Italy
| | | | - Sharon J Hutchinson
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK; Clinical and Protecting Health Directorate, Public Health Scotland, Glasgow, UK
| | - Bruno Sangro
- Liver Unit, Clinica Universidad de Navarra-IDISNA and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Pamplona, Spain
| | - Natasha K Martin
- Division of Infectious Diseases and Global Public Health, University of California San Diego, San Diego, CA, USA; Population Health Sciences, University of Bristol, Bristol, UK
| | - Michele Cecchini
- Health Division, Organisation for Economic Co-operation and Development, Paris, France
| | - Mae Ashworth Dirac
- Department of Health Metrics Sciences, University of Washington, Seattle, WA, USA; Department of Family Medicine, University of Washington, Seattle, WA, USA; Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA
| | - Annalisa Belloni
- Health Economics and Modelling Division, Public Health England, London, UK
| | - Miquel Serra-Burriel
- Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland
| | - Cyriel Y Ponsioen
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam University Medical Centers, Amsterdam, Netherlands
| | - Brittney Sheena
- Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA
| | - Alienor Lerouge
- Health Division, Organisation for Economic Co-operation and Development, Paris, France
| | - Marion Devaux
- Health Division, Organisation for Economic Co-operation and Development, Paris, France
| | - Nick Scott
- Disease Elimination Program, Burnet Institute, Melbourne, VIC, Australia
| | - Margaret Hellard
- Disease Elimination Program, Burnet Institute, Melbourne, VIC, Australia; Department of Infectious Diseases, Alfred Hospital, Melbourne, VIC, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia; Doherty Institute and School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia
| | - Henkjan J Verkade
- Paediatric Gastroenterology and Hepatology, Department of Paediatrics, University Medical Centre Groningen, University of Groningen, Netherlands; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany
| | - Ekkehard Sturm
- Division of Paediatric Gastroenterology and Hepatology, University Children's Hospital Tübingen, Tübingen, Germany; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany
| | | | | | - Chris D Byrne
- Department of Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, UK; Southampton National Institute for Health Research, Biomedical Research Centre, University Hospital Southampton and Southampton General Hospital, Southampton, UK
| | - Giovanni Targher
- Department of Medicine, Section of Endocrinology, Diabetes, and Metabolism, University of Verona, Verona, Italy
| | - Aviad Tur-Sinai
- Department of Health Systems Management, The Max Stern Yezreel Valley College, Yezreel Valley, Israel
| | - Damon Barrett
- School of Public Health and Community Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | | | - Tatjana Reic
- European Liver Patients Organization, Brussels, Belgium; Croatian Society for Liver Diseases-Hepatos, Split, Croatia
| | | | - Tim Rhodes
- London School of Hygiene & Tropical Medicine, London, UK
| | - Carla Treloar
- Centre for Social Research in Health, University of New South Wales, Sydney, NSW, Australia
| | - Claus Petersen
- Department of Pediatric Surgery, Hannover Medical School, Hannover, Germany
| | - Christoph Schramm
- Martin Zeitz Center for Rare Diseases, Hamburg Center for Translational Immunology (HCTI), and First Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Poland
| | - Marieta Y Simonova
- Department of Gastroenterology, HPB Surgery and Transplantation, Clinic of Gastroentrology, Military Medical Academy, Sofia, Bulgaria
| | - Albert Pares
- Liver Unit, Hospital Clinic of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; CIBEREHD, Madrid, Spain
| | - Philip Johnson
- Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
| | - Alessandro Cucchetti
- Department of Medical and Surgical Sciences-DIMEC, Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Isabel Graupera
- Liver Unit, Hospital Clinic of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; CIBEREHD, Madrid, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Spain
| | - Christos Lionis
- Clinic of Social and Family Medicine, Medical School, University of Crete, Heraklion, Greece
| | - Elisa Pose
- Liver Unit, Hospital Clinic of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Spain
| | - Núria Fabrellas
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; CIBEREHD, Madrid, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Spain
| | - Ann T Ma
- Liver Unit, Hospital Clinic of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Juan M Mendive
- Prevention and Health Promotion Research Network (redIAPP), Institute of Health Carlos III, Madrid, Spain; La Mina Health Centre, Catalan Institute of Health (ICS), Barcelona, Spain
| | - Vincenzo Mazzaferro
- HPB Surgery and Liver Transplantation, Istituto Nazionale Tumori IRCCS Foundation (INT), Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
| | - Harry Rutter
- Department of Social and Policy Sciences, University of Bath, Bath, UK
| | - Helena Cortez-Pinto
- Clínica Universitária de Gastrenterologia and Laboratório de Nutrição, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| | - Deirdre Kelly
- Liver Unit, Birmingham Women's and Children's Hospital and University of Birmingham, UK
| | - Robyn Burton
- Alcohol, Drugs, Tobacco and Justice Division, Public Health England, London, UK
| | - Jeffrey V Lazarus
- Barcelona Institute for Global Health (ISGlobal), Hospital Clínic, Barcelona, Spain
| | - Pere Ginès
- Liver Unit, Hospital Clinic of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; CIBEREHD, Madrid, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Spain
| | - Maria Buti
- CIBEREHD del Instituto de Salud Carlos III, Madrid, Spain; Liver Unit, Hospital Universitario Valle Hebron, Barcelona, Spain
| | - Philip N Newsome
- National Institute for Health Research Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, UK
| | - Patrizia Burra
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
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Nan Y, Xu X, Gao Y, Wang R, Li W, Yang M, Liu L, Duan Z, Jia J, Wei L, Zhuang H. Consensus on the secondary prevention of primary liver cancer. Hepatol Int 2021; 15:1289-1300. [PMID: 34846705 PMCID: PMC8712303 DOI: 10.1007/s12072-021-10259-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Accepted: 09/29/2021] [Indexed: 02/06/2023]
Abstract
To standardize the effective prevention, surveillance, and diagnosis of primary liver cancer, the Chinese Society of Hepatology, Chinese Medical Association, invited clinical experts and methodologists to develop the Consensus on the Secondary Prevention of Primary Liver Cancer, which was based on the clinical and scientific advances on hepatocellular carcinoma. The purpose is to provide a current basis for the prevention, surveillance, and early diagnosis of primary liver cancer in patients with chronic liver diseases.
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Affiliation(s)
- Yuemin Nan
- Present Address: Department of Traditional and Western Medical Hepatology, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051 China
| | - Xiaoyuan Xu
- Department of Infectious Diseases, Peking University First Hospital, Beijing, 100034 China
| | - Yanhang Gao
- Department of Hepatology, The First Hospital of Jilin University, Changchun, 130021 China
| | - Rongqi Wang
- Present Address: Department of Traditional and Western Medical Hepatology, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051 China
| | - Wengang Li
- Radiation Oncology Centre, The Fifth Medical Centre of Chinese PLA General Hospital, Beijing, 100039 China
| | - Ming Yang
- Peking University Hepatology Institute, Peking University People’s Hospital, Beijing, China
| | - Lingdi Liu
- Present Address: Department of Traditional and Western Medical Hepatology, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051 China
| | - Zhongping Duan
- Artificial Liver Centre, Beijing You-An Hospital, Capital Medical University, Beijing, China
| | - Jidong Jia
- Liver Research Centre, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Lai Wei
- Hepatopancreatobiliary Centre, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Hui Zhuang
- Department of Microbiology and Centre for Infectious Diseases, Peking University Health Science Centre, Beijing, China
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Qing X, Xu W, Zong J, Du X, Peng H, Zhang Y. Emerging treatment modalities for systemic therapy in hepatocellular carcinoma. Biomark Res 2021; 9:64. [PMID: 34419152 PMCID: PMC8380325 DOI: 10.1186/s40364-021-00319-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2021] [Accepted: 08/05/2021] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) has long been a major global clinical problem as one of the most common malignant tumours with a high rate of recurrence and mortality. Although potentially curative therapies are available for the early and intermediate stages, the treatment of patients with advanced HCC remains to be resolved. Fortunately, the past few years have shown the emergence of successful systemic therapies to treat HCC. At the molecular level, HCC is a heterogeneous disease, and current research on the molecular characteristics of HCC has revealed numerous therapeutic targets. Targeted agents based on signalling molecules have been successfully supported in clinical trials, and molecular targeted therapy has already become a milestone for disease management in patients with HCC. Immunotherapy, a viable approach for the treatment of HCC, recognizes the antigens expressed by the tumour and treats the tumour using the immune system of the host, making it both selective and specific. In addition, the pipeline for HCC is evolving towards combination therapies with promising clinical outcomes. More drugs designed to focus on specific pathways and immune checkpoints are being developed in the clinic. It has been demonstrated that some drugs can improve the prognosis of patients with HCC in first- or second-line settings, and these drugs have been approved by the Food and Drug Administration or are nearing approval. This review describes targeting pathways and systemic treatment strategies in HCC and summarizes effective targeted and immune-based drugs for patients with HCC and the problems encountered.
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Affiliation(s)
- Xin Qing
- Department of General Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, China
| | - Wenjing Xu
- Department of General Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, China
| | - Jingjing Zong
- Department of General Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, China
| | - Xuanlong Du
- Department of General Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, China
| | - Hao Peng
- Department of General Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, China
| | - Yewei Zhang
- Department of General Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, China.
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Bae H, Lee SA, Choi JW, Hwang SH, Park S, Park MS. Effectiveness of Hepatocellular Carcinoma Surveillance and an Optimal Surveillance Interval: Nationwide Cohort of Korea. Yonsei Med J 2021; 62:758-766. [PMID: 34296554 PMCID: PMC8298874 DOI: 10.3349/ymj.2021.62.8.758] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 04/28/2021] [Accepted: 05/29/2021] [Indexed: 12/24/2022] Open
Abstract
PURPOSE To assess associations between surveillance intervals in a national hepatocellular carcinoma (HCC) surveillance program and receiving curative treatment and mortality using nationwide cohort data for Korea. MATERIALS AND METHODS Using the National Health Insurance Service Database of Korea, we retrospectively identified 3201852 patients, the target population of the national HCC surveillance program, between 2008 and 2017. After exclusion, a total of 64674 HCC patients were divided based on surveillance intervals: never screened, ≤6 months (6M), 7-12 months (1Y), 13-24 months (2Y), and 25-36 months (3Y). Associations for surveillance interval with the chance to receive curative therapy and all-cause mortality were analyzed. RESULTS The 6M group (51.9%) received curative therapy more often than the other groups (1Y, 48.3%; 2Y, 43.8%; 3Y, 41.3%; never screened, 34.5%). Odds ratio for receiving curative therapy among the other surveillance interval groups (1Y, 0.87; 2Y, 0.76; 3Y, 0.77; never screened, 0.57; p<0.001) were significantly lower than that of the 6M group. The hazard ratios (HRs) of all-cause mortality were 1.07, 1.14, and 1.37 for 2Y, 3Y, and never screened groups. The HR for the 1Y group (0.96; p=0.092) was not significantly different, and it was lower (0.91; p<0.001) than that of the 6M group after adjustment for lead-time bias. Curative therapy was associated with survival benefits (HR, 0.26; p<0.001). CONCLUSION HCC surveillance, especially at a surveillance interval of 6 months, increases the chance to receive curative therapy.
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Affiliation(s)
- Heejin Bae
- Department of Radiology and Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Korea
| | - Sang Ah Lee
- Big Data Strategy Department, National Health Insurance Service, Wonju, Korea
| | - Jong Won Choi
- Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Korea
| | - Shin Hye Hwang
- Department of Radiology, Yongin Severance Hospital, Yongin, Korea
| | - Sumi Park
- Department of Radiology, National Health Insurance Service Ilsan Hospital, Goyang, Korea.
| | - Mi Suk Park
- Department of Radiology and Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Korea.
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Kudo M, Kawamura Y, Hasegawa K, Tateishi R, Kariyama K, Shiina S, Toyoda H, Imai Y, Hiraoka A, Ikeda M, Izumi N, Moriguchi M, Ogasawara S, Minami Y, Ueshima K, Murakami T, Miyayama S, Nakashima O, Yano H, Sakamoto M, Hatano E, Shimada M, Kokudo N, Mochida S, Takehara T. Management of Hepatocellular Carcinoma in Japan: JSH Consensus Statements and Recommendations 2021 Update. Liver Cancer 2021; 10:181-223. [PMID: 34239808 PMCID: PMC8237791 DOI: 10.1159/000514174] [Citation(s) in RCA: 423] [Impact Index Per Article: 105.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Accepted: 12/23/2020] [Indexed: 02/06/2023] Open
Abstract
The Clinical Practice Manual for Hepatocellular Carcinoma was published based on evidence confirmed by the Evidence-based Clinical Practice Guidelines for Hepatocellular Carcinoma along with consensus opinion among a Japan Society of Hepatology (JSH) expert panel on hepatocellular carcinoma (HCC). Since the JSH Clinical Practice Guidelines are based on original articles with extremely high levels of evidence, expert opinions on HCC management in clinical practice or consensus on newly developed treatments are not included. However, the practice manual incorporates the literature based on clinical data, expert opinion, and real-world clinical practice currently conducted in Japan to facilitate its use by clinicians. Alongside each revision of the JSH Guidelines, we issued an update to the manual, with the first edition of the manual published in 2007, the second edition in 2010, the third edition in 2015, and the fourth edition in 2020, which includes the 2017 edition of the JSH Guideline. This article is an excerpt from the fourth edition of the HCC Clinical Practice Manual focusing on pathology, diagnosis, and treatment of HCC. It is designed as a practical manual different from the latest version of the JSH Clinical Practice Guidelines. This practice manual was written by an expert panel from the JSH, with emphasis on the consensus statements and recommendations for the management of HCC proposed by the JSH expert panel. In this article, we included newly developed clinical practices that are relatively common among Japanese experts in this field, although all of their statements are not associated with a high level of evidence, but these practices are likely to be incorporated into guidelines in the future. To write this article, coauthors from different institutions drafted the content and then critically reviewed each other's work. The revised content was then critically reviewed by the Board of Directors and the Planning and Public Relations Committee of JSH before publication to confirm the consensus statements and recommendations. The consensus statements and recommendations presented in this report represent measures actually being conducted at the highest-level HCC treatment centers in Japan. We hope this article provides insight into the actual situation of HCC practice in Japan, thereby affecting the global practice pattern in the management of HCC.
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Affiliation(s)
- Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan,*Masatoshi Kudo,
| | | | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Ryosuke Tateishi
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kazuya Kariyama
- Department of Gastroenterology, Okayama City Hospital, Okayama, Japan
| | - Shuichiro Shiina
- Department of Gastroenterology, Juntendo University, Tokyo, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Gifu, Japan
| | - Yasuharu Imai
- Department of Gastroenterology, Ikeda Municipal Hospital, Osaka, Japan
| | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Masafumi Ikeda
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Michihisa Moriguchi
- Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Sadahisa Ogasawara
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Yasunori Minami
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Kazuomi Ueshima
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Takamichi Murakami
- Department of Radiology, Kobe University Graduate School of Medicine, Hyogo, Japan
| | - Shiro Miyayama
- Department of Diagnostic Radiology, Fukui-ken Saiseikai Hospital, Fukui, Japan
| | - Osamu Nakashima
- Department of Clinical Laboratory Medicine, Kurume University Hospital, Kurume, Japan
| | - Hirohisa Yano
- Department of Pathology, Kurume University School of Medicine, Kurume, Japan
| | - Michiie Sakamoto
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Etsuro Hatano
- Department of Gastroenterological Surgery, Hyogo College of Medicine, Nishinomiya, Japan
| | - Mitsuo Shimada
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Norihiro Kokudo
- Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan
| | - Satoshi Mochida
- Department of Gastroenterology and Hepatology, Saitama Medical University, Saitama, Japan
| | - Tetsuo Takehara
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
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Nguyen ALT, Nguyen HTT, Yee KC, Palmer AJ, Blizzard CL, de Graaff B. A Systematic Review and Narrative Synthesis of Health Economic Evaluations of Hepatocellular Carcinoma Screening Strategies. VALUE IN HEALTH : THE JOURNAL OF THE INTERNATIONAL SOCIETY FOR PHARMACOECONOMICS AND OUTCOMES RESEARCH 2021; 24:733-743. [PMID: 33933243 DOI: 10.1016/j.jval.2020.11.014] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/03/2020] [Revised: 09/24/2020] [Accepted: 11/17/2020] [Indexed: 05/02/2023]
Abstract
OBJECTIVES Many economic evaluations of hepatocellular carcinoma (HCC) screenings have been conducted; however, these vary substantially with regards to screening strategies, patient group, and setting. This review aims to report the current knowledge of the cost-effectiveness of screening and describe the published data. METHODS We conducted a search of biomedical and health economic databases up to July 2020. We included full and partial health economic studies if they evaluated the costs or outcomes of HCC screening strategies. RESULTS The review included 43 studies. Due to significant heterogeneity in key aspects across the studies, a narrative synthesis was conducted. Most studies reported using ultrasound or alpha fetoprotein as screening strategies. Screening intervals were mostly annual or biannual. Incidence, diagnostic performance, and health state utility values were the most critical parameters affecting the cost-effectiveness of screening. The majority of studies reported HCC screening to be cost-effective, with the biannual ultrasound + alpha fetoprotein standing out as the most cost-effective strategy. However, few studies considered the utilization rate, and none considered the diagnostic performance of ultrasound in the context of central adiposity. Computed tomography and magnetic resonance imaging were also evaluated, but its cost-effectiveness was still controversial. CONCLUSIONS Although many studies suggested HCC screening was cost-effective, substantial limitations of the quality of these studies means the results should be interpreted with caution. Future modeling studies should consider the impact of central adiposity on the precision of ultrasound, real-world utilization rates and projections of increased HCC incidence.
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Affiliation(s)
- Anh Le Tuan Nguyen
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia
| | - Hoa Thi Thu Nguyen
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia
| | - Kwang Chien Yee
- School of Medicine, University of Tasmania, Hobart, Tasmania, Australia
| | - Andrew J Palmer
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia; Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia
| | | | - Barbara de Graaff
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
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Epidemiology of HPB malignancy in the elderly. Eur J Surg Oncol 2021; 47:503-513. [PMID: 32360064 DOI: 10.1016/j.ejso.2020.03.222] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2020] [Revised: 03/17/2020] [Accepted: 03/26/2020] [Indexed: 02/08/2023] Open
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Abstract
INTRODUCTION Hepatocellular carcinoma (HCC) is an increasingly common disease with liver transplant (LT) the best long-term therapy for early stage disease. We will review the data for assessing risk and managing recurrence for patients undergoing LT for HCC. AREAS COVERED In this review, we will provide an overview of methods of patient risk stratification in the post-transplant period, the data around surveillance for HCC recurrence, and the evidence for and against post-LT adjuvant treatment strategies. Finally, we will provide data regarding treatment options for patients with HCC recurrence after LT. Using an extensive search of original papers and society guidelines, this paper provides a comprehensive review of the data for assessing risk and managing recurrence for patients undergoing LT for HCC. EXPERT OPINION The development of multiple post-transplant prognostic scoring systems have allowed for improved assessment of recurrence risk and stratification of patients. However, the ability to translate this information into surveillance and therapeutic strategies that improve patient outcomes still have to be fully demonstrated. Post-LT immunosuppression strategies have been implemented in order to attempt to reduce this risk. Evidence-based strategies for managing recurrent HCC are evolving. We expect that with further understanding of individual patient characteristics will allow for optimal therapeutic selection.
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Affiliation(s)
- Daniel Hoffman
- Department of Surgery, University of California , San Francisco, CA, USA
| | - Neil Mehta
- Division of Gastroenterology, Department of Medicine, University of California , San Francisco, CA, USA
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A comparison of prognoses between surgical resection and radiofrequency ablation therapy for patients with hepatocellular carcinoma and esophagogastric varices. Sci Rep 2020; 10:17259. [PMID: 33057213 PMCID: PMC7560860 DOI: 10.1038/s41598-020-74424-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Accepted: 09/15/2020] [Indexed: 02/08/2023] Open
Abstract
There has been insufficient investigation of the differences in long-term outcomes between surgical resection (SR) and radiofrequency ablation (RFA) among patients with hepatocellular carcinoma (HCC) and esophagogastric varices (EGV). We retrospectively enrolled 251 patients with treatment-naïve HCC and EGV who underwent SR or RFA as a first-line treatment. Prognostic factors were analyzed using a Cox proportional hazards model. A total of 68 patients underwent SR, and the remaining 183 patients received RFA. Patients who underwent SR were younger, had better liver functional reserves, and had larger tumors. After a median follow-up duration of 45.1 months, 151 patients died. The cumulative 5-year overall survival (OS) rate was significantly higher among patients who underwent SR than those treated with RFA (66.7% vs. 36.8%, p < 0.001). Multivariate analysis showed that age > 65 years, multiple tumors, RFA, albumin bilirubin grade > 1, and the occurrence of major peri-procedural morbidity were the independent risk factors that are predictive of poor OS. In conclusion, SR could be recommended as a first-line treatment modality for HCC patients with EGV if the patients are carefully selected and liver function is well preserved.
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Yang JD, Luu M, Singal AG, Noureddin M, Kuo A, Ayoub WS, Sundaram V, Kotler H, Kim IK, Todo T, Voidonikolas G, Brennan TV, Kosari K, Klein AS, Hendifar A, Lu SC, Nissen NN, Gong J. Factors Associated With Detection and Survival of T1 Hepatocellular Carcinoma in the United States: National Cancer Database Analysis. J Natl Compr Canc Netw 2020; 18:1210-1220. [DOI: 10.6004/jnccn.2020.7564] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2020] [Accepted: 03/25/2020] [Indexed: 11/17/2022]
Abstract
Background: It remains unknown to what extent hepatocellular carcinomas (HCCs) are detected very early (T1 stage; ie, unifocal <2 cm) in the United States. The aim of this study was to investigate the trends and factors associated with very early detection of HCC and resultant outcomes. Methods: Patients with HCC diagnosed from 2004 through 2014 were identified from the National Cancer Database. Logistic regression was used to identify factors associated with T1 HCC detection, and Cox proportional hazard analyses identified factors associated with overall survival among patients with T1 HCC. Results: Of 110,182 eligible patients, the proportion with T1 HCC increased from 2.6% in 2004 to 6.8% in 2014 (P<.01). The strongest correlate of T1 HCC detection was receipt of care at an academic institution (odds ratio, 3.51; 95% CI, 2.31–5.34). Older age, lack of insurance, high Model for End-Stage Liver Disease (MELD) score, high alpha-fetoprotein, increased Charlson-Deyo comorbidity score, and nonsurgical treatment were associated with increased mortality, and care at an academic center (hazard ratio [HR], 0.27; 95% CI, 0.15–0.48) was associated with reduced mortality in patients with T1 HCC. Liver transplantation (HR, 0.27; 95% CI, 0.20–0.37) and surgical resection (HR, 0.67; 95% CI, 0.48–0.93) were independently associated with improved survival compared with ablation. This is the first study to examine the trend of T1 HCC using the National Cancer Database, which covers approximately 70% of all cancer diagnoses in the United States, using robust statistical analyses. Limitations of the study include a retrospective study design using administrative data and some pertinent data that were not available. Conclusions: Despite increases over time, <10% of HCCs are detected at T1 stage. The strongest correlates of survival among patients with T1 HCC are receiving care at an academic institution and surgical treatment.
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Affiliation(s)
- Ju Dong Yang
- 1Division of Digestive and Liver Diseases,
- 2Comprehensive Transplant Center,
- 3Samuel Oschin Comprehensive Cancer Institute, and
| | - Michael Luu
- 4Biostatistics and Bioinformatics Research Center, Cedars-Sinai Medical Center, West Hollywood, California; and
| | - Amit G. Singal
- 5Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Mazen Noureddin
- 1Division of Digestive and Liver Diseases,
- 2Comprehensive Transplant Center,
| | - Alexander Kuo
- 1Division of Digestive and Liver Diseases,
- 2Comprehensive Transplant Center,
| | - Walid S. Ayoub
- 1Division of Digestive and Liver Diseases,
- 2Comprehensive Transplant Center,
| | - Vinay Sundaram
- 1Division of Digestive and Liver Diseases,
- 2Comprehensive Transplant Center,
| | | | | | | | | | | | | | | | | | - Shelly C. Lu
- 1Division of Digestive and Liver Diseases,
- 3Samuel Oschin Comprehensive Cancer Institute, and
| | - Nicholas N. Nissen
- 2Comprehensive Transplant Center,
- 3Samuel Oschin Comprehensive Cancer Institute, and
| | - Jun Gong
- 3Samuel Oschin Comprehensive Cancer Institute, and
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Kudo M. A Paradigm Change in the Treatment Strategy for Hepatocellular Carcinoma. Liver Cancer 2020; 9:367-377. [PMID: 32999864 PMCID: PMC7506281 DOI: 10.1159/000507934] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Accepted: 04/16/2020] [Indexed: 02/04/2023] Open
Affiliation(s)
- Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
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Park HJ, Jang HY, Kim SY, Lee SJ, Won HJ, Byun JH, Choi SH, Lee SS, An J, Lim YS. Non-enhanced magnetic resonance imaging as a surveillance tool for hepatocellular carcinoma: Comparison with ultrasound. J Hepatol 2020; 72:718-724. [PMID: 31836549 DOI: 10.1016/j.jhep.2019.12.001] [Citation(s) in RCA: 96] [Impact Index Per Article: 19.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Revised: 11/27/2019] [Accepted: 12/01/2019] [Indexed: 12/25/2022]
Abstract
BACKGROUND & AIMS Recently revised international guidelines for hepatocellular carcinoma (HCC) suggest that patients with inadequate ultrasonography be assessed by alternative imaging modalities. Non-enhanced MRI has potential as a surveillance tool based on the short scan times required and the absence of contrast agent-associated risks. This study compared the performance of non-enhanced MRI and ultrasonography for HCC surveillance in high-risk patients. METHODS We included 382 high-risk patients in a prospective cohort who underwent 1 to 3 rounds of paired gadoxetic acid-enhanced MRI and ultrasonography. Non-enhanced MRI, consisting of diffusion-weighted imaging (DWI) and T2-weighted imaging, was simulated and retrospectively analyzed, with results considered positive when lesion(s) ≥1 cm showed diffusion restriction or mild-moderate T2 hyperintensity. Ultrasonography results were retrieved from patient records. HCC was diagnosed histologically and/or radiologically. Sensitivity, positive predictive value (PPV), specificity, and negative predictive value (NPV) were evaluated using generalized estimating equations. RESULTS Forty-eight HCCs were diagnosed in 43 patients. Per-lesion and per-exam sensitivities of non-enhanced MRI were 77.1% and 79.1%, respectively, which were higher than those achieved with ultrasonography (25.0% and 27.9%, respectively, p <0.001). Specificities of non-enhanced MRI (97.9%) and ultrasonography (94.5%) differed significantly (p <0.001). NPV was higher for non-enhanced MRI (99.1%) than ultrasonography (96.9%). Per-lesion and per-exam PPVs were higher for non-enhanced MRI (56.9% and 61.8%, respectively) than for ultrasonography (16.7% and 17.7%, respectively). The estimated scan time of non-enhanced MRI was <6 min. CONCLUSION Based on its good performance, short scan times, and the lack of contrast agent-associated risks, non-enhanced MRI is a promising option for HCC surveillance in high-risk patients. LAY SUMMARY Recently revised international guidelines for hepatocellular carcinoma (HCC) suggest that selected patients with inadequate surveillance on ultrasonography be assessed by alternative imaging modalities such as computed tomography or magnetic resonance imaging (MRI). Herein, we show that MRI without contrast agents performed significantly better than ultrasonography for HCC surveillance in high-risk patients. Given this good performance, as well as short scan times and the lack of contrast agent-associated risks, non-enhanced MRI is a promising option for HCC surveillance in high-risk patients.
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Affiliation(s)
- Hyo Jung Park
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Hye Young Jang
- Department of Radiology, National Cancer Center, Gyeonggi-do, Republic of Korea
| | - So Yeon Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
| | - So Jung Lee
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Hyung Jin Won
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jae Ho Byun
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sang Hyun Choi
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Seung Soo Lee
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jihyun An
- Department of Gastroenterology and Hepatology, Hanyang University of Medicine, Guri, Republic of Korea
| | - Young-Suk Lim
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Numata K. On the occasion of publication of the feature on differential diagnosis and treatment of hepatocellular carcinoma: the role of ultrasound. J Med Ultrason (2001) 2020; 47:211-213. [DOI: 10.1007/s10396-020-01015-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
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Ultrasound fusion imaging technologies for guidance in ablation therapy for liver cancer. J Med Ultrason (2001) 2020; 47:257-263. [PMID: 32125577 DOI: 10.1007/s10396-020-01006-w] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Accepted: 01/05/2020] [Indexed: 12/17/2022]
Abstract
With advances in imaging technology, images from ultrasound (US) and computed tomography (CT) or magnetic resonance imaging (MRI) can be displayed simultaneously and in real time, according to the angle of the transducer. CT/MR-US fusion imaging improves the visualization of inconspicuous hepatocellular carcinoma (HCC) and helps us to understand the three-dimensional relationship between the liver vasculature and HCC. US fusion imaging guidance facilitates improvement in the treatment response for HCC with poor conspicuity, and the rates of technical success of ablation and local tumor progression for inconspicuous HCC range from 94.4 to 100% and 0 to 8.3%, respectively. Moreover, the development of image fusion has made it possible to compare and overlay pre- and post-ablation US images. This US-US fusion imaging allows side-by-side comparison of the ablative margin, while US-US overlay fusion can visualize the ablative margin because the tumor image is projected onto the ablative hyperechoic zone. Thus, US-US overlay fusion guidance is highly effective for safety margin achievement in local ablation therapy for HCC, providing a lower risk of local tumor progression. This manuscript reviews the current status of ultrasound fusion imaging for percutaneous ablation therapy of HCC.
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Sarin SK, Kumar M, Eslam M, George J, Al Mahtab M, Akbar SMF, Jia J, Tian Q, Aggarwal R, Muljono DH, Omata M, Ooka Y, Han KH, Lee HW, Jafri W, Butt AS, Chong CH, Lim SG, Pwu RF, Chen DS. Liver diseases in the Asia-Pacific region: a Lancet Gastroenterology & Hepatology Commission. Lancet Gastroenterol Hepatol 2020; 5:167-228. [PMID: 31852635 PMCID: PMC7164809 DOI: 10.1016/s2468-1253(19)30342-5] [Citation(s) in RCA: 355] [Impact Index Per Article: 71.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Revised: 07/20/2019] [Accepted: 08/02/2019] [Indexed: 02/06/2023]
Abstract
The Asia-Pacific region is home to more than half of the global population and accounted for 62·6% of global deaths due to liver diseases in 2015. 54·3% of global deaths due to cirrhosis, 72·7% of global deaths due to hepatocellular carcinoma, and more than two-thirds of the global burden of acute viral hepatitis occurred in this region in 2015. Chronic hepatitis B virus (HBV) infection caused more than half of the deaths due to cirrhosis in the region, followed by alcohol consumption (20·8%), non-alcoholic fatty liver disease (NAFLD; 12·1%), and chronic infection with hepatitis C virus (HCV; 15·7%). In 2015, HBV accounted for about half the cases of hepatocellular carcinoma in the region. Preventive strategies for viral hepatitis-related liver disease include increasing access to clean drinking water and sanitation. HBV vaccination programmes for neonates have been implemented by all countries, although birth-dose coverage is extremely suboptimal in some. Availability of screening tests for blood and tissue, donor recall policies, and harm reduction strategies are in their initial stages in most countries. Many governments have put HBV and HCV drugs on their essential medicines lists and the availability of generic versions of these drugs has reduced costs. Efforts to eliminate viral hepatitis as a public health threat, together with the rapid increase in per-capita alcohol consumption in countries and the epidemic of obesity, are expected to change the spectrum of liver diseases in the Asia-Pacific region in the near future. The increasing burden of alcohol-related liver diseases can be contained through government policies to limit consumption and promote less harmful patterns of alcohol use, which are in place in some countries but need to be enforced more strictly. Steps are needed to control obesity and NAFLD, including policies to promote healthy lifestyles and regulate the food industry. Inadequate infrastructure and insufficient health-care personnel trained in liver diseases are issues that also need to be addressed in the Asia-Pacific region. The policy response of most governments to liver diseases has thus far been inadequate and poorly funded. There must be a renewed focus on prevention, early detection, timely referral, and research into the best means to introduce and improve health interventions to reduce the burden of liver diseases in the Asia-Pacific region.
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Affiliation(s)
- Shiv K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi, India.
| | - Manoj Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi, India
| | - Mohammed Eslam
- Storr Liver Centre, The Westmead Institute for Medical Research, University of Sydney and Westmead Hospital, Westmead, Australia
| | - Jacob George
- Storr Liver Centre, The Westmead Institute for Medical Research, University of Sydney and Westmead Hospital, Westmead, Australia
| | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Sheikh M Fazle Akbar
- Department of Pathology, Ehime University Proteo-Science Center, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medial University, Beijing, China
| | - Qiuju Tian
- Liver Research Center, Beijing Friendship Hospital, Capital Medial University, Beijing, China
| | - Rakesh Aggarwal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | | | - Masao Omata
- Department of Gastroenterology, Yamanashi Central Hospital, Yamanashi, Japan; University of Tokyo, Tokyo, Japan
| | - Yoshihiko Ooka
- Department of Gastroenterology, Chiba University Hospital, Chiba, Japan
| | - Kwang-Hyub Han
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Wasim Jafri
- Department of Medicine, Section of Gastroenterology, The Aga Khan University, Karachi, Pakistan
| | - Amna S Butt
- Department of Medicine, Section of Gastroenterology, The Aga Khan University, Karachi, Pakistan
| | - Chern H Chong
- Division of Gastroenterology & Hepatology, National University Health System, Singapore; Division of General Medicine, Woodlands Health Campus, Singapore
| | - Seng G Lim
- Division of Gastroenterology & Hepatology, National University Health System, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Raoh-Fang Pwu
- National Hepatitis C Program Office, Ministry of Health and Welfare, Taipei, Taiwan
| | - Ding-Shinn Chen
- Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan; Genomics Research Center, Academia Sinica, Taipei, Taiwan
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Affiliation(s)
- Linda L Wong
- Department of Surgery, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA
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Kudo M, Izumi N, Kubo S, Kokudo N, Sakamoto M, Shiina S, Tateishi R, Nakashima O, Murakami T, Matsuyama Y, Takahashi A, Miyata H, Takayama T. Report of the 20th Nationwide follow-up survey of primary liver cancer in Japan. Hepatol Res 2020; 50:15-46. [PMID: 31655492 PMCID: PMC7003938 DOI: 10.1111/hepr.13438] [Citation(s) in RCA: 111] [Impact Index Per Article: 22.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Revised: 09/01/2019] [Accepted: 09/03/2019] [Indexed: 12/12/2022]
Abstract
In the 20th Nationwide Follow-up Survey of Primary Liver Cancer in Japan, data from 21 075 new patients and 40 769 previously followed patients were compiled from 544 institutions over a 2-year period from 1 January 2008 to 31 December 2009. Compared with the previous 19th survey, the population of patients with hepatocellular carcinoma (HCC) was older at the time of clinical diagnosis, included more female patients, included more patients with non-B non-C HCC, had smaller tumor diameters and more frequently received radiofrequency ablation as local ablation therapy. Cumulative survival rates were calculated for HCC, intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma (combined HCC and intrahepatic cholangiocarcinoma) by treatment type and by background characteristics for patients newly registered between 1998 and 2009 whose final outcome was survival or death. Cumulative survival rates for HCC were calculated by dividing patients by combinations of background factors (number of tumors, tumor diameter, and Child-Pugh grade) and by treatment types (hepatectomy, local ablation therapy, and transcatheter arterial chemoembolization). Cumulative survival rates and median overall survival in patients treated by resection, transcatheter arterial chemoembolization, and local ablation therapy were calculated. The same values were also calculated by the registration date by dividing patients newly registered between 1978 and 2009 into four time period groups . The results of the analysis show that the prognosis of HCC is improving dramatically. It is expected that the data obtained from this nationwide follow-up survey will contribute to advancing clinical research, including the design of clinical trials, as well as the treatment strategy of primary liver cancer in the clinical practice setting.
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Affiliation(s)
- Masatoshi Kudo
- Follow‐up Survey Committee, Liver Cancer Study Group ofJapan
- Department of Gastroenterology and HepatologyKindai University Faculty of MedicineOsaka‐SayamaJapan
| | - Namiki Izumi
- Follow‐up Survey Committee, Liver Cancer Study Group ofJapan
- Department of GastroenterologyMusashino Red Cross HospitalTokyoJapan
| | - Shoji Kubo
- Follow‐up Survey Committee, Liver Cancer Study Group ofJapan
- Department of Hepato‐Biliary‐Pancreatic SurgeryOsaka City University Graduate School of MedicineOsakaJapan
| | - Norihiro Kokudo
- Follow‐up Survey Committee, Liver Cancer Study Group ofJapan
- National Center for Global Health and MedicineTokyoJapan
| | - Michiie Sakamoto
- Follow‐up Survey Committee, Liver Cancer Study Group ofJapan
- Department of PathologyKeio University School of MedicineTokyoJapan
| | - Shuichiro Shiina
- Follow‐up Survey Committee, Liver Cancer Study Group ofJapan
- Department of GastroenterologyJuntendo University School of MedicineTokyoJapan
| | - Ryosuke Tateishi
- Follow‐up Survey Committee, Liver Cancer Study Group ofJapan
- Department of Gastroenterology Graduate School of Medicine,The University of TokyoTokyoJapan
| | - Osamu Nakashima
- Follow‐up Survey Committee, Liver Cancer Study Group ofJapan
- Department of Clinical Laboratory MedicineKurume University HospitalKurumeJapan
| | - Takamichi Murakami
- Follow‐up Survey Committee, Liver Cancer Study Group ofJapan
- Department of Diagnostic and Interventional RadiologyKobe University Graduate School of MedicineKobeJapan
| | - Yutaka Matsuyama
- Follow‐up Survey Committee, Liver Cancer Study Group ofJapan
- Department of Biostatistics, School of Public HealthUniversity of TokyoTokyoJapan
| | - Arata Takahashi
- National Clinical DatabaseTokyoJapan
- Department of Healthcare Quality Assessment, Graduate School of MedicineThe University of TokyoTokyoJapan
| | - Hiroaki Miyata
- National Clinical DatabaseTokyoJapan
- Department of Healthcare Quality Assessment, Graduate School of MedicineThe University of TokyoTokyoJapan
| | - Tadatoshi Takayama
- Follow‐up Survey Committee, Liver Cancer Study Group ofJapan
- Department of Digestive SurgeryNihon University School of MedicineTokyoJapan
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Kudo M. Management of Hepatocellular Carcinoma in Japan: Current Trends. Liver Cancer 2020; 9:1-5. [PMID: 32071904 PMCID: PMC7024863 DOI: 10.1159/000505370] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Accepted: 12/11/2019] [Indexed: 02/04/2023] Open
Affiliation(s)
- Masatoshi Kudo
- *Masatoshi Kudo, Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 337-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511 (Japan), E-Mail
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Kariyama K, Nouso K, Wakuta A, Oonishi A, Toyoda H, Tada T, Hiraoka A, Tsuji K, Itobayashi E, Ishikawa T, Takaguchi K, Tsutsui A, Shimada N, Kumada T. Treatment of Intermediate-Stage Hepatocellular Carcinoma in Japan: Position of Curative Therapies. Liver Cancer 2020; 9:41-49. [PMID: 32071908 PMCID: PMC7024876 DOI: 10.1159/000502479] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2019] [Accepted: 08/02/2019] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Transcatheter arterial chemoembolization (TACE) is the standard therapy for intermediate-stage (IM) hepatocellular carcinoma (HCC). However, IM-HCC includes various clinical conditions, and various therapies were conducted in practice. In this study, we retrospectively analyzed the actually conducted treatments for IM-HCC and their efficacies to elucidate the treatment strategies suitable for IM-HCC. METHODS This study included 627 IM-HCC of 5,260 HCC from 9 hospitals. We examined the treatment strategies of these patients and analyzed the efficacy of each therapy with the Cox proportional hazard model and propensity score-matched analysis. RESULTS Liver resection, radiofrequency ablation (RFA), and TACE were performed in 165, 108, and 351 patients, respectively. Liver resection and RFA were preferably selected in cases of Barcelona Clinic Liver Cancer (BCLC)-B1/B2, and patient survival was significantly longer than in those treated with TACE (p< 0.0001). However, no beneficial effect of these active therapies was observed in cases of BCLC-B3/B4. Multivariate analysis revealed that surgical resection (hazard ratio = 0.384) and RFA (hazard ratio = 0.597) were negative risk factors for survival. Propensity score-matching analysis revealed that -survival of RFA-treated patients was longer than that of TACE-treated patients (p = 0.036). CONCLUSION RFA and surgical resection were effective for IM-HCC, particularly in BCLC-B1/B2 cases.
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Affiliation(s)
- Kazuya Kariyama
- aDepartment of Gastroenterology and Liver Disease Center, Okayama City Hospital, Okayama, Japan
| | - Kazuhiro Nouso
- aDepartment of Gastroenterology and Liver Disease Center, Okayama City Hospital, Okayama, Japan
| | - Akiko Wakuta
- aDepartment of Gastroenterology and Liver Disease Center, Okayama City Hospital, Okayama, Japan
| | - Ayano Oonishi
- aDepartment of Gastroenterology and Liver Disease Center, Okayama City Hospital, Okayama, Japan
| | - Hidenori Toyoda
- bDepartment of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Gifu, Japan
| | - Toshifumi Tada
- bDepartment of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Gifu, Japan
| | - Atsushi Hiraoka
- cGastroenterology Center, Ehime Prefectural Central Hospital, Ehime, Japan
| | - Kunihiko Tsuji
- dCenter of Gastroenterology, Teine Keijinkai Hospital, Hokkaido, Japan
| | - Ei Itobayashi
- eDepartment of Gastroenterology, Asahi General Hospital, Chiba, Japan
| | - Toru Ishikawa
- fDepartment of Gastroenterology, Saiseikai Niigata Daini Hospital, Niigata, Japan
| | - Koichi Takaguchi
- gDepartment of Hepatology, Kagawa Prefectural Central Hospital, Kagawa, Japan
| | - Akemi Tsutsui
- gDepartment of Hepatology, Kagawa Prefectural Central Hospital, Kagawa, Japan
| | - Noritomo Shimada
- hDepartment of Gastroenterology and Hepatology, Otakanomori Hospital, Chiba, Japan
| | - Takashi Kumada
- bDepartment of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Gifu, Japan
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Yamashita T, Kudo M, Ikeda K, Izumi N, Tateishi R, Ikeda M, Aikata H, Kawaguchi Y, Wada Y, Numata K, Inaba Y, Kuromatsu R, Kobayashi M, Okusaka T, Tamai T, Kitamura C, Saito K, Haruna K, Okita K, Kumada H. REFLECT-a phase 3 trial comparing efficacy and safety of lenvatinib to sorafenib for the treatment of unresectable hepatocellular carcinoma: an analysis of Japanese subset. J Gastroenterol 2020; 55:113-122. [PMID: 31720835 PMCID: PMC6942573 DOI: 10.1007/s00535-019-01642-1] [Citation(s) in RCA: 138] [Impact Index Per Article: 27.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Accepted: 10/27/2019] [Indexed: 02/04/2023]
Abstract
BACKGROUND A phase 3, multinational, randomized, non-inferiority trial (REFLECT) compared the efficacy and safety of lenvatinib (LEN) and sorafenib (SOR) in patients with unresectable hepatocellular carcinoma (uHCC). LEN had an effect on overall survival (OS) compared to SOR, statistically confirmed by non-inferiority [OS: median = 13.6 months vs. 12.3 months; hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.79-1.06], and demonstrated statistically significant improvements in progression-free survival (PFS) and the objective response rate (ORR) in the overall population. The results of a subset analysis that evaluated the efficacy and safety of LEN and SOR in the Japanese population are reported. METHODS The intent-to-treat population enrolled in Japan was analyzed. RESULTS Of 954 patients in the overall population, 168 Japanese patients were assigned to the LEN arm (N = 81) or the SOR arm (N = 87). Median OS was 17.6 months for LEN vs. 17.8 months for SOR (HR 0.90; 95% CI 0.62-1.29). LEN showed statistically significant improvements over SOR in PFS (7.2 months vs. 4.6 months) and ORR (29.6% vs. 6.9%). The relative dose intensity of LEN and SOR in the Japanese population was lower than in the overall population. Frequently observed, related adverse events included palmar-plantar erythrodysaesthesia syndrome (PPES), hypertension, decreased appetite, and proteinuria in the LEN arm, and PPES, hypertension, diarrhea, and alopecia in the SOR arm. CONCLUSIONS The efficacy and safety of LEN in the Japanese population were similar to those in the overall population of REFLECT. With manageable adverse events, LEN is a new treatment option for Japanese patients with uHCC. TRIAL REGISTRATION ID ClinicalTrials.gov. No. NCT01761266.
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Affiliation(s)
- Tatsuya Yamashita
- grid.9707.90000 0001 2308 3329Department of Gastroenterology, Kanazawa University, Kanazawa, Japan
| | - Masatoshi Kudo
- grid.258622.90000 0004 1936 9967Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Kenji Ikeda
- grid.410813.f0000 0004 1764 6940Department of Hepatology, Toranomon Hospital, Tokyo, Japan
| | - Namiki Izumi
- grid.416332.10000 0000 9887 307XDepartment of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan
| | - Ryosuke Tateishi
- grid.26999.3d0000 0001 2151 536XDepartment of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Masafumi Ikeda
- grid.272242.30000 0001 2168 5385Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Hiroshi Aikata
- grid.257022.00000 0000 8711 3200Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan
| | - Yasunori Kawaguchi
- Department of Hepatobiliary and Pancreatology, Saga-Ken Medical Center Koseikan, Saga, Japan ,Department of Gastroenterology, Asakura Medical Association Hospital, Asakura, Japan
| | - Yoshiyuki Wada
- grid.415613.4Department of Hepato-Biliary-Pancreatic Surgery, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
| | - Kazushi Numata
- grid.413045.70000 0004 0467 212XGastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Yoshitaka Inaba
- grid.410800.d0000 0001 0722 8444Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Ryoko Kuromatsu
- grid.410781.b0000 0001 0706 0776Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Masahiro Kobayashi
- grid.410813.f0000 0004 1764 6940Department of Hepatology, Toranomon Hospital, Tokyo, Japan
| | - Takuji Okusaka
- grid.272242.30000 0001 2168 5385Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Toshiyuki Tamai
- grid.418765.90000 0004 1756 5390Eisai Co., Ltd., Tokyo, Japan
| | | | - Kenichi Saito
- grid.418765.90000 0004 1756 5390Eisai Co., Ltd., Tokyo, Japan
| | - Katsuya Haruna
- grid.418765.90000 0004 1756 5390Eisai Co., Ltd., Tokyo, Japan
| | - Kiwamu Okita
- Department of Hepatology, Shunan Memorial Hospital, Kudamatsu, Japan
| | - Hiromitsu Kumada
- grid.410813.f0000 0004 1764 6940Department of Hepatology, Toranomon Hospital, Tokyo, Japan
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