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Jun YJ, Lee M, Chun HS, Kim TH. [Non-Invasive Test for Assessment of Liver Fibrosis in Chronic Hepatitis B]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2024; 84:206-214. [PMID: 39582308 DOI: 10.4166/kjg.2024.106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Accepted: 10/05/2024] [Indexed: 11/26/2024]
Abstract
Chronic hepatitis B (CHB) is a high-risk condition that requires continuous monitoring and appropriate management during the natural course of the disease. In particular, the assessment of liver fibrosis is crucial for determining the optimal timing of antiviral therapy, evaluating the treatment response, and predicting the occurrence and prognosis of hepatocellular carcinoma (HCC) in the management of CHB. Although a liver biopsy is the gold standard for diagnosing liver inflammation, steatosis, and fibrosis, there has been a growing trend in the use of non-invasive tests, such as serum biomarkers, transient elastography, and shear wave elastography in CHB patients. This review provides a summary of the key research findings on the use of serum biomarkers and transient elastography in assessing liver fibrosis, monitoring the disease progression, and predicting the prognosis of CHB patients, with an emphasis on their clinical applicability.
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Affiliation(s)
- Ye Ji Jun
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Ewha Womans University Seoul Hospital, Seoul, Korea
| | - Minjong Lee
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Ewha Womans University Seoul Hospital, Seoul, Korea
| | - Ho Soo Chun
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Ewha Womans University Seoul Hospital, Seoul, Korea
| | - Tae Hun Kim
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Ewha Womans University Seoul Hospital, Seoul, Korea
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Kim MN, Han JW, An J, Kim BK, Jin YJ, Kim SS, Lee M, Lee HA, Cho Y, Kim HY, Shin YR, Yu JH, Kim MY, Choi Y, Chon YE, Cho EJ, Lee EJ, Kim SG, Kim W, Jun DW, Kim SU. KASL clinical practice guidelines for noninvasive tests to assess liver fibrosis in chronic liver disease. Clin Mol Hepatol 2024; 30:S5-S105. [PMID: 39159947 PMCID: PMC11493350 DOI: 10.3350/cmh.2024.0506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 08/12/2024] [Accepted: 08/16/2024] [Indexed: 08/21/2024] Open
Affiliation(s)
- Mi Na Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Ji Won Han
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jihyun An
- Department of Gastroenterology and Hepatology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Young-Joo Jin
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
| | - Seung-seob Kim
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Minjong Lee
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Han Ah Lee
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
| | - Hee Yeon Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yu Rim Shin
- Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Jung Hwan Yu
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
| | - Moon Young Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
| | - Young Eun Chon
- Department of Internal Medicine, Institute of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - Eun Ju Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Eun Joo Lee
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea
| | - Sang Gyune Kim
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Won Kim
- Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Dae Won Jun
- Department of Internal Medicine, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - on behalf of The Korean Association for the Study of the Liver (KASL)
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Gastroenterology and Hepatology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
- Department of Internal Medicine, Institute of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam, Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
- Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, Korea
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Jin YJ, Kim HY, Suh YJ, Lee CH, Yu JH, Kim MN, Han JW, Lee HA, An J, Chon YE, Jun DW, Choi M, Kim SU. Risk assessment of hepatitis B virus-related hepatocellular carcinoma development using vibration-controlled transient elastography: Systematic review and meta-analysis. Clin Mol Hepatol 2024; 30:S159-S171. [PMID: 39038958 PMCID: PMC11493361 DOI: 10.3350/cmh.2024.0163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 07/19/2024] [Accepted: 07/19/2024] [Indexed: 07/24/2024] Open
Abstract
BACKGROUNDS/AIMS Liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE) can assess fibrotic burden in chronic liver diseases. The systematic review and meta-analysis was conducted to determine whether LSM using VCTE can predict the risk of development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients. METHODS A systematic literature search of the Ovid-Medline, EMBASE, Cochrane, and KoreaMed databases (from January 2010 to June 2023) was conducted. Of the 1,345 individual studies identified, 10 studies that used VCTE were finally registered. Hazard ratios (HRs) and the 95% confidence intervals (CIs) were considered summary estimates of treatment effect sizes of ≥11 kilopascal (kPa) standard for HCC development. Meta-analysis was performed using the restricted Maximum Likelihood random effects model. RESULTS Among the ten studies, data for risk ratios for HCC development could be obtained from nine studies. When analyzed for the nine studies, the HR for HCC development was high at 3.33 (95% CI, 2.45-4.54) in CHB patients with a baseline LSM of ≥11 kPa compared to patients who did not. In ten studies included, LSM of ≥11 kPa showed the sensitivity and specificity for predicting HCC development were 61% (95% CI, 50-71%) and 78% (95% CI, 66-86%), respectively, and the diagnostic accuracy was 0.74 (95% CI, 0.70-0.77). CONCLUSION The risk of HCC development was elevated in CHB patients with VCTE-determined LSM of ≥11 kPa. This finding suggests that VCTE-determined LSM values may aid the risk prediction of HCC development in CHB patients.
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Affiliation(s)
- Young-Joo Jin
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
| | - Hee Yeon Kim
- Department of Internal Medicine, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Young Ju Suh
- Department of Biomedical Sciences, College of Medicine, Inha University, Incheon, Korea
| | - Chae Hyeon Lee
- Pharmacometrics Institute for Practical Education and Training (PIPET), College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jung Hwan Yu
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
| | - Mi Na Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Ji Won Han
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea
| | - Han Ah Lee
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Jihyun An
- Department of Gastroenterology and Hepatology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Young Eun Chon
- Department of Internal Medicine, Institute of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - Dae Won Jun
- Department of Gastroenterology, Hanyang University, College of Medicine, Seoul, Korea
| | - Miyoung Choi
- Division of Healthcare Technology Assessment Research, National Evidence-based Healthcare, Collaborating Agency, Seoul, Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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Li ZB, Chen DD, Jia YF, He QJ, Cui L, Du FX, Kang YJ, Feng X, He M, Jin XY, Chen J, Wang Y, Ji D, Lau G, Wu SG. Risk factors related to low-level viraemia in chronic hepatitis B patients receiving entecavir treatment. Front Cell Infect Microbiol 2024; 14:1413589. [PMID: 39170987 PMCID: PMC11335720 DOI: 10.3389/fcimb.2024.1413589] [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: 04/07/2024] [Accepted: 07/08/2024] [Indexed: 08/23/2024] Open
Abstract
Background About 20% of on-treatment patients with chronic hepatitis B (CHB) experienced low-level viraemia (LLV), which is associated with persistent low-grade inflammation, fibrosis progression, and increased risk of hepatocellular carcinoma. We aimed to investigate the high-risk factors related to LLV. Methods In this retrospective study, patients receiving entecavir (ETV) treatment from January 2018 to January 2023 were enrolled, and were divided into a LLV (HBV DNA 20-2000 IU/mL) cohort and a complete virological response (CVR) (HBV DNA < 20 IU/mL) cohort according to the virological response at week 48 posttreatment. Treatment baseline characteristics were retrieved from electronic medical records. Multivariate logistic regression was performed. Results Totally, 1653 patients were enrolled, male patients accounted for 73.0%; the median age was 44 years; the mean HBV DNA level was 5.9 Log10 IU/ml. Among them, 472 (28.6%) experienced LLV. Multivariate analysis showed that HBeAg positivity (OR = 2.650, 95% CI: 2.000-3.511, p < 0.001), HBV DNA ≥ 6.0 Log10 IU/mL (OR = 1.370, 95% CI: 1.054-1.780, p = 0.019), qHBsAg ≥ 9000 IU/mL (OR = 4.472, 95% CI: 3.410-5.866, p < 0.001), cirrhosis (OR = 1.650, 95% CI: 1.234-2.207, P = 0.001), LSM ≥ 13.0 kPa (OR = 1.644, 95% CI: 1.203-2.246, p = 0.002), and PLT < 100×109/L (OR = 1.450, 95% CI: 1.094-1.922, p = 0.010) at baseline were related to the development of LLV. Conclusions High HBV DNA/HBsAg quantification/LSM, low PLT, HBeAg positivity, and liver cirrhosis were high-risk factors associated with LLV in patients receiving entecavir treatment.
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Affiliation(s)
- Zhong-Bin Li
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Dan-Dan Chen
- Department II of Infectious Diseases (Hepatology), The Second People’s Hospital of Jingzhou City, Jingzhou, China
| | - Yun-Fei Jia
- Department of Hepatobiliary & Gastrointestinal, Henan Province Hospital of Traditional Chinese Medicine, Zhengzhou, China
| | - Qing-Juan He
- Department II of Gastroenterology, The Eighth People’s Hospital of Qingdao, Qingdao, China
| | - Li Cui
- Department of Emergency, the Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Feng-Xia Du
- Department of Pharmacy, Medical Supplies Center of PLA General Hospital, Beijing, China
| | - Yao-Jie Kang
- Department of Medical Quality Management, the Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Xin Feng
- Out-patient Department, Hospital of Beijing Information Science and Technology University, Beijing, China
| | - Mengwen He
- 302 Clinical Medical School, Peking University, Beijing, China
| | - Xue-Yuan Jin
- Department of Medical Quality Management, the Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Jing Chen
- JCSchool of Public Health and Primary Care, Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Yudong Wang
- Humanity and Health Clinical Trial Center, Humanity and Health Medical Group, Hong Kong, Hong Kong SAR, China
| | - Dong Ji
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Beijing, China
- 302 Clinical Medical School, Peking University, Beijing, China
| | - George Lau
- Humanity and Health Clinical Trial Center, Humanity and Health Medical Group, Hong Kong, Hong Kong SAR, China
| | - Shu-Gao Wu
- Out-patient Department, Hospital of Beijing Information Science and Technology University, Beijing, China
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Yin Y, Feng W, Chen J, Chen X, Wang G, Wang S, Xu X, Nie Y, Fan D, Wu K, Xia L. Immunosuppressive tumor microenvironment in the progression, metastasis, and therapy of hepatocellular carcinoma: from bench to bedside. Exp Hematol Oncol 2024; 13:72. [PMID: 39085965 PMCID: PMC11292955 DOI: 10.1186/s40164-024-00539-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Accepted: 07/10/2024] [Indexed: 08/02/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is a highly heterogeneous malignancy with high incidence, recurrence, and metastasis rates. The emergence of immunotherapy has improved the treatment of advanced HCC, but problems such as drug resistance and immune-related adverse events still exist in clinical practice. The immunosuppressive tumor microenvironment (TME) of HCC restricts the efficacy of immunotherapy and is essential for HCC progression and metastasis. Therefore, it is necessary to elucidate the mechanisms behind immunosuppressive TME to develop and apply immunotherapy. This review systematically summarizes the pathogenesis of HCC, the formation of the highly heterogeneous TME, and the mechanisms by which the immunosuppressive TME accelerates HCC progression and metastasis. We also review the status of HCC immunotherapy and further discuss the existing challenges and potential therapeutic strategies targeting immunosuppressive TME. We hope to inspire optimizing and innovating immunotherapeutic strategies by comprehensively understanding the structure and function of immunosuppressive TME in HCC.
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Affiliation(s)
- Yue Yin
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China
| | - Weibo Feng
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China
| | - Jie Chen
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China
| | - Xilang Chen
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China
| | - Guodong Wang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China
| | - Shuai Wang
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China
| | - Xiao Xu
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China
| | - Yongzhan Nie
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China.
| | - Daiming Fan
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China.
| | - Kaichun Wu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China.
| | - Limin Xia
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China.
- Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China.
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Kim BK, Ahn SH. Prediction model of hepatitis B virus-related hepatocellular carcinoma in patients receiving antiviral therapy. J Formos Med Assoc 2023; 122:1238-1246. [PMID: 37330305 DOI: 10.1016/j.jfma.2023.05.029] [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: 12/01/2022] [Revised: 05/15/2023] [Accepted: 05/24/2023] [Indexed: 06/19/2023] Open
Abstract
Chronic hepatitis B virus (HBV) infection, which ultimately leads to liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC), remains a significant disease burden worldwide. Despite the use of antiviral therapy (AVT) using oral nucleos(t)ide analogs (NUCs) with high genetic barriers, the risk of HCC development cannot be completely eliminated. Therefore, bi-annual surveillance of HCC using abdominal ultrasonography with or without tumor markers is recommended for at-risk populations. For a more precise assessment of future HCC risk at the individual level, many HCC prediction models have been proposed in the era of potent AVT with promising results. It allows prognostication according to the risk of HCC development, for example, low-vs. intermediate-vs. high-risk groups. Most of these models have the advantage of high negative predictive values for HCC development, allowing exemption from biannual HCC screening. Recently, non-invasive surrogate markers for liver fibrosis, such as vibration-controlled transient elastography, have been introduced as integral components of the equations, providing better predictive performance in general. Furthermore, beyond the conventional statistical methods that primarily depend on multi-variable Cox regression analyses based on the previous literature, newer techniques using artificial intelligence have also been applied in the design of HCC prediction models. Here, we aimed to review the HCC risk prediction models that were developed in the era of potent AVT and validated among independent cohorts to address the clinical unmet needs, as well as comment on future direction to establish the individual HCC risk more precisely.
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Affiliation(s)
- Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea; Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea; Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea.
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Roy AM, Iyer R, Chakraborty S. The extracellular matrix in hepatocellular carcinoma: Mechanisms and therapeutic vulnerability. Cell Rep Med 2023; 4:101170. [PMID: 37652015 PMCID: PMC10518608 DOI: 10.1016/j.xcrm.2023.101170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Revised: 04/04/2023] [Accepted: 08/03/2023] [Indexed: 09/02/2023]
Abstract
The tumor microenvironment (TME) is influenced by a "disorganized" extracellular matrix (ECM) that sensitizes cancer cells toward mechanical stress, signaling, and structural alterations. In hepatocellular carcinoma (HCC), lack of knowledge about key ECM proteins driving the TME refractory to targeted therapies poses a barrier to the identification of new therapeutic targets. Herein, we discuss the contributions of various ECM components that impact hepatocytes and their surrounding support network during tumorigenesis. In addition, the underpinnings by which ECM proteins transduce mechanical signals to the liver TME are detailed. Finally, in view of the bidirectional feedback between the ECM, transformed hepatocytes, and immune cells, we highlight the potential role of the ECM disorganization process in shaping responses to immune checkpoint inhibitors and targeted therapies. Our comprehensive characterization of these ECM components may provide a roadmap for innovative therapeutic approaches to restrain HCC.
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Affiliation(s)
- Arya Mariam Roy
- Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
| | - Renuka Iyer
- Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
| | - Sayan Chakraborty
- Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA; Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA; Program of Developmental Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14263.
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Zhong X, Long H, Chen L, Xie Y, Shi Y, Peng J, Zheng R, Su L, Duan Y, Xie X, Lin M. Stiffness on shear wave elastography as a potential microenvironment biomarker for predicting tumor recurrence in HBV-related hepatocellular carcinoma. Insights Imaging 2023; 14:147. [PMID: 37697029 PMCID: PMC10495298 DOI: 10.1186/s13244-023-01505-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Accepted: 08/16/2023] [Indexed: 09/13/2023] Open
Abstract
BACKGROUND To explore the pathologic basis and prognostic value of tumor and liver stiffness measured pre-operatively by two-dimensional shear wave elastography (2D-SWE) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients who undergo hepatic resection. METHODS A total of 191 HBV-infected patients with solitary resectable HCC were prospectively enrolled. The stiffness of intratumoral tissue, peritumoral tissue, adjacent liver tissue, and distant liver tissue was evaluated by 2D-SWE. The correlations between stiffness and pathological characteristics were analyzed in 114 patients. The predictive value of stiffness for recurrence-free survival (RFS) was evaluated, and Cutoff Finder was used for determining optimal cut-off stiffness values. Cox proportional hazards analysis was used to identify independent predictors of RFS. RESULTS Pathologically, intratumoral stiffness was associated with stroma proportion and microvascular invasion (MVI) while peritumoral stiffness was associated with tumor size, capsule, and MVI. Adjacent liver stiffness was correlated with capsule and liver fibrosis stage while distant liver stiffness was correlated with liver fibrosis stage. Peritumoral stiffness, adjacent liver stiffness, and distant liver stiffness were all correlated to RFS (all p < 0.05). Higher peritumoral stiffness (> 49.4 kPa) (HR = 1.822, p = 0.023) and higher adjacent liver stiffness (> 24.1 kPa) (HR = 1.792, p = 0.048) were significant independent predictors of worse RFS, along with tumor size and MVI. The nomogram based on these variables showed a C-index of 0.77 for RFS prediction. CONCLUSIONS Stiffness measured by 2D-SWE could be a tumor microenvironment and tumor invasiveness biomarker. Peritumoral stiffness and adjacent liver stiffness showed important values in predicting tumor recurrence after curative resection in HBV-related HCC. CLINICAL RELEVANCE STATEMENT Tumor and liver stiffness measured by two-dimensional shear wave elastography serve as imaging biomarkers for predicting hepatocellular carcinoma recurrence, reflecting biological behavior and tumor microenvironment. KEY POINTS • Stiffness measured by two-dimensional shear wave elastography is a useful biomarker of tumor microenvironment and invasiveness. • Higher stiffness indicated more aggressive behavior of hepatocellular carcinoma. • The study showed the prognostic value of peritumoral stiffness and adjacent liver stiffness for recurrence-free survival. • The nomogram integrating peritumoral stiffness, adjacent liver stiffness, tumor size, and microvascular invasion showed a C-index of 0.77.
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Affiliation(s)
- Xian Zhong
- Department of Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Second Road, Guangzhou, 510080, China
| | - Haiyi Long
- Department of Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Second Road, Guangzhou, 510080, China
| | - Lili Chen
- Department of Pathology, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Second Road, Guangzhou, 510080, China
| | - Yuhua Xie
- Department of Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Second Road, Guangzhou, 510080, China
| | - Yifan Shi
- Department of Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Second Road, Guangzhou, 510080, China
| | - Jianyun Peng
- Department of Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Second Road, Guangzhou, 510080, China
| | - Ruiying Zheng
- Department of Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Second Road, Guangzhou, 510080, China
| | - Liya Su
- Department of Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Second Road, Guangzhou, 510080, China
| | - Yu Duan
- Department of Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Second Road, Guangzhou, 510080, China
| | - Xiaoyan Xie
- Department of Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Second Road, Guangzhou, 510080, China
| | - Manxia Lin
- Department of Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Second Road, Guangzhou, 510080, China.
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Yoo SH, Kim M, Kim S, Lee JI, Lee KS, Lee HW, Lim JH. The care cascade for hepatitis C virus and prognosis of chronic hepatitis C patients treated with antiviral agents in a tertiary hospital. BMC Gastroenterol 2023; 23:116. [PMID: 37041473 PMCID: PMC10088268 DOI: 10.1186/s12876-023-02750-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Accepted: 03/28/2023] [Indexed: 04/13/2023] Open
Abstract
BACKGROUND Some studies have analyzed the frequency of HCV RNA testing and actual treatment among anti-HCV positive patients in Korea, which has a low prevalence of HCV infection. This study aimed to analyze the diagnosis process, treatment results, and prognosis according to care cascade in patients who are anti-HCV positive. METHODS Three thousand two hundred fifty-three anti-HCV positive patients presented to a tertiary hospital between January 2005 and December 2020. The number of patients who underwent HCV RNA testing, treatment, and proportion of sustained virologic response (SVR) according to the type of antivirals was investigated. We investigated the cumulative incidence of hepatocellular carcinoma (HCC) and liver cirrhosis. RESULTS Of a total of 3,253 people, 1,177 (36.2%) underwent HCV RNA testing and 858 (72.9%) were positive for HCV RNA. 494 (57.6%) of HCV RNA positive patients received antiviral treatment, and 443 (89.7%) of initiated hepatitis C treatment experienced SVR. Of the 421 treated patients, 16 (14.2%) developed HCC. The cumulative incidence of HCC at 15 years was significantly different according to the presence of liver cirrhosis (10/83, 29.5% vs. 6/338, 10.8%, p < 0.001). The cumulative incidences of HCC or liver cirrhosis did not show significant differences according to the presence of SVR12 (14/388, 13.2% vs. 2/33, 52.5%, p = 0.084, 21/319, 15.0%, vs. 3/22, 28.7%, p = 0.051). CONCLUSIONS Owing to the introduction of direct-acting antivirals, high SVR12 was achieved, but the proportion of anti-HCV positive patients who received HCV RNA testing and treatment was not high. HCC surveillance after SVR12 is recommended for chronic hepatitis C patients with cirrhosis.
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Affiliation(s)
- Sung Hwan Yoo
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 211, Eonju-Ro, Gangnam-Gu, Seoul, 06273, Republic of Korea
| | - Myung Kim
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 211, Eonju-Ro, Gangnam-Gu, Seoul, 06273, Republic of Korea
| | - Sora Kim
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 211, Eonju-Ro, Gangnam-Gu, Seoul, 06273, Republic of Korea
| | - Jung Il Lee
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 211, Eonju-Ro, Gangnam-Gu, Seoul, 06273, Republic of Korea
| | - Kwan Sik Lee
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 211, Eonju-Ro, Gangnam-Gu, Seoul, 06273, Republic of Korea
| | - Hyun Woong Lee
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 211, Eonju-Ro, Gangnam-Gu, Seoul, 06273, Republic of Korea.
| | - Jin Hong Lim
- Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, 211, Eonju-Ro, Gangnam-Gu, Seoul, 06273, Republic of Korea.
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Song W, Yoo SH, Jang J, Baik SJ, Lee BK, Lee HW, Park JS. Association between Sarcopenic Obesity Status and Nonalcoholic Fatty Liver Disease and Fibrosis. Gut Liver 2023; 17:130-138. [PMID: 36472070 PMCID: PMC9840924 DOI: 10.5009/gnl220041] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 04/10/2022] [Accepted: 05/13/2022] [Indexed: 12/12/2022] Open
Abstract
Background/Aims There are no data regarding the association between sarcopenic obesity status and nonalcoholic fatty liver disease (NAFLD) and NAFLD-associated liver fibrosis. Therefore, we aimed to investigate the relationship between sarcopenic obesity status (sarcopenia only, obesity only, and sarcopenic obesity) and NAFLD and liver fibrosis in Korean adults. Methods In total, 2,191 subjects completed a health checkup program, including abdominal ultrasonography and FibroScan. Subjects were classified into the following four categories: optimal body composition (nonobese and nonsarcopenic), sarcopenia only (nonobese), obesity only (nonsarcopenic), and sarcopenic obesity. Sarcopenic obesity was stratified by the skeletal muscle mass index and body fat using bioelectrical impedance analysis. NAFLD was diagnosed by ultrasonography, and liver fibrosis was assessed using transient elastography in subjects with NAFLD. Results The prevalence of NAFLD and liver fibrosis significantly increased according to the sarcopenic obesity status. In the logistic regression analysis, after adjusting for multiple risk factors, the odds ratio (OR) for the risk of NAFLD was largest in the sarcopenic obesity group (OR, 3.68; 95% confidence interval [CI], 2.94 to 4.60), followed by the obesity only (OR, 2.25; 95% CI, 1.67 to 3.03) and sarcopenia only (OR, 1.92; 95% CI, 1.30 to 2.84) groups, when compared with the optimal group. Additionally, liver fibrosis was independently associated with sarcopenic obesity status (OR 4.69, 95% CI 1.95 to 11.29; OR 4.17, 95% CI 1.56 to 11.17; OR 3.80, 95% CI 0.86 to 16.75, respectively). Conclusions These results demonstrated that sarcopenic obesity was independently associated with NAFLD and liver fibrosis and increased the risk of NAFLD and liver fibrosis more than obesity or sarcopenia alone.
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Affiliation(s)
- Wolhwa Song
- Divisions of Endocrinology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Sung Hwan Yoo
- Divisions of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Jinsun Jang
- Divisions of Endocrinology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Su Jung Baik
- Healthcare Research Team, Health Promotion Center, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Byoung Kwon Lee
- Healthcare Research Team, Health Promotion Center, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Hyun Woong Lee
- Divisions of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea,Hyun Woong Lee, ORCIDhttps://orcid.org/0000-0002-6958-3035, E-mail
| | - Jong Suk Park
- Divisions of Endocrinology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea,Corresponding AuthorJong Suk Park, ORCIDhttps://orcid.org/0000-0002-5385-1373, E-mail
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Entecavir plus Biejia-Ruangan compound reduces the risk of hepatocellular carcinoma in Chinese patients with chronic hepatitis B. J Hepatol 2022; 77:1515-1524. [PMID: 35985545 DOI: 10.1016/j.jhep.2022.07.018] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 07/11/2022] [Accepted: 07/19/2022] [Indexed: 12/16/2022]
Abstract
BACKGROUND & AIMS Chronic hepatitis B (CHB) and liver fibrosis are associated with a high risk of hepatocellular carcinoma (HCC) development. We assessed whether entecavir (ETV) plus Biejia-Ruangan compound (BRC), an anti-fibrotic traditional Chinese medicine, can further reduce the risk of HCC in treatment-naïve Chinese patients with CHB and an Ishak fibrosis score of ≥3 points derived from our parent double-blind randomized placebo-controlled trial. METHODS After a 72-week comparison between ETV+BRC and ETV+placebo treatment, participants were eligible to enter an open-label treatment phase and were followed up every 6 months. The primary [secondary] endpoints were the incidence of HCC [liver-related deaths, non-HCC events, and non-liver-related deaths]. Modified intention-to-treat (mITT), intention-to-treat (ITT), and per-protocol (PP) populations were defined for the time-to-event analysis. RESULTS A total of 1,000 patients were recruited; the median age was 42.0 years; 69.9% were male and 58.3% were HBeAg positive. In the mITT population, the 7-year cumulative incidence of HCC [liver-related deaths] was 4.7% [0.2%] for ETV+BRC, which was significantly lower than 9.3% [2.2%] for ETV monotherapy (p = 0.008 [p = 0.030]). Notably, ETV+BRC treatment yielded a lower incidence of HCC in those who did not achieve regression of fibrosis at week 72 than ETV monotherapy (p = 0.018). There were no differences in the other 2 secondary endpoints or safety profiles between the groups. Multivariable Cox proportional regression analysis, including the treatment allocation as a parameter, also demonstrated that ETV+BRC treatment was associated with a reduced incidence of HCC. The ITT and PP analyses showed consistent results. CONCLUSIONS ETV plus BRC combination treatment could further reduce the risk of HCC and liver-related deaths in patients with CHB and advanced fibrosis or cirrhosis, which may have important clinical implications for HCC prevention. LAY SUMMARY Patients with chronic hepatitis B virus infection are at an increased risk of developing liver cancer (specifically hepatocellular carcinoma [HCC]). While there are effective antiviral treatments that can suppress the virus in chronically infected patients, the risk of HCC remains. Herein, we show that adding a traditional Chinese medicine called Biejia-Ruangan compound to an antiviral reduced the risk of HCC in patients with chronic hepatitis B.
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Collagen Remodeling along Cancer Progression Providing a Novel Opportunity for Cancer Diagnosis and Treatment. Int J Mol Sci 2022; 23:ijms231810509. [PMID: 36142424 PMCID: PMC9502421 DOI: 10.3390/ijms231810509] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 09/01/2022] [Accepted: 09/07/2022] [Indexed: 12/12/2022] Open
Abstract
The extracellular matrix (ECM) is a significant factor in cancer progression. Collagens, as the main component of the ECM, are greatly remodeled alongside cancer development. More and more studies have confirmed that collagens changed from a barrier to providing assistance in cancer development. In this course, collagens cause remodeling alongside cancer progression, which in turn, promotes cancer development. The interaction between collagens and tumor cells is complex with biochemical and mechanical signals intervention through activating diverse signal pathways. As the mechanism gradually clears, it becomes a new target to find opportunities to diagnose and treat cancer. In this review, we investigated the process of collagen remodeling in cancer progression and discussed the interaction between collagens and cancer cells. Several typical effects associated with collagens were highlighted in the review, such as fibrillation in precancerous lesions, enhancing ECM stiffness, promoting angiogenesis, and guiding invasion. Then, the values of cancer diagnosis and prognosis were focused on. It is worth noting that several generated fragments in serum were reported to be able to be biomarkers for cancer diagnosis and prognosis, which is beneficial for clinic detection. At a glance, a variety of reported biomarkers were summarized. Many collagen-associated targets and drugs have been reported for cancer treatment in recent years. The new targets and related drugs were discussed in the review. The mass data were collected and classified by mechanism. Overall, the interaction of collagens and tumor cells is complicated, in which the mechanisms are not completely clear. A lot of collagen-associated biomarkers are excavated for cancer diagnosis. However, new therapeutic targets and related drugs are almost in clinical trials, with merely a few in clinical applications. So, more efforts are needed in collagens-associated studies and drug development for cancer research and treatment.
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Mowla A, Belford R, Köhn-Gaone J, Main N, Tirnitz-Parker JEE, Yeoh GC, Kennedy BF. Biomechanical assessment of chronic liver injury using quantitative micro-elastography. BIOMEDICAL OPTICS EXPRESS 2022; 13:5050-5066. [PMID: 36187256 PMCID: PMC9484444 DOI: 10.1364/boe.467684] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 08/17/2022] [Accepted: 08/19/2022] [Indexed: 06/16/2023]
Abstract
Hepatocellular carcinoma is one of the most lethal cancers worldwide, causing almost 700,000 deaths annually. It mainly arises from cirrhosis, which, in turn, results from chronic injury to liver cells and corresponding fibrotic changes. Although it is known that chronic liver injury increases the elasticity of liver tissue, the role of increased elasticity of the microenvironment as a possible hepatocarcinogen is yet to be investigated. One reason for this is the paucity of imaging techniques capable of mapping the micro-scale elasticity variation in liver and correlating that with cancerous mechanisms on the cellular scale. The clinical techniques of ultrasound elastography and magnetic resonance elastography typically do not provide micro-scale resolution, while atomic force microscopy can only assess the elasticity of a limited number of cells. We propose quantitative micro-elastography (QME) for mapping the micro-scale elasticity of liver tissue into images known as micro-elastograms, and therefore, as a technique capable of correlating the micro-environment elasticity of tissue with cellular scale cancerous mechanisms in liver. We performed QME on 13 freshly excised healthy and diseased mouse livers and present micro-elastograms, together with co-registered histology, in four representative cases. Our results indicate a significant increase in the mean (×6.3) and standard deviation (×6.0) of elasticity caused by chronic liver injury and demonstrate that the onset and progression of pathological features such as fibrosis, hepatocyte damage, and immune cell infiltration correlate with localized variations in micro-elastograms.
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Affiliation(s)
- Alireza Mowla
- BRITElab, Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, and Centre for Medical Research, The University of Western Australia, Perth, WA 6009, Australia
- Department of Electrical, Electronic & Computer Engineering, School of Engineering, The University of Western Australia, Perth, WA 6009, Australia
| | - Rose Belford
- BRITElab, Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, and Centre for Medical Research, The University of Western Australia, Perth, WA 6009, Australia
- Department of Electrical, Electronic & Computer Engineering, School of Engineering, The University of Western Australia, Perth, WA 6009, Australia
| | - Julia Köhn-Gaone
- Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Perth, WA 6102, Australia
| | - Nathan Main
- Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Perth, WA 6102, Australia
| | - Janina E. E. Tirnitz-Parker
- Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Perth, WA 6102, Australia
- Centre for Medical Research, Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, WA 6009, Australia
| | - George C. Yeoh
- Centre for Medical Research, Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, WA 6009, Australia
- School of Molecular Sciences, The University of Western Australia, Perth, WA 6009, Australia
- Centre for Cell Therapy and Regenerative Medicine, School of Biomedical Sciences, The University of Western Australia, Perth, WA 6009, Australia
| | - Brendan F. Kennedy
- BRITElab, Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, and Centre for Medical Research, The University of Western Australia, Perth, WA 6009, Australia
- Department of Electrical, Electronic & Computer Engineering, School of Engineering, The University of Western Australia, Perth, WA 6009, Australia
- Australian Research Council Centre for Personalised Therapeutics Technologies, Australia
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Wei S, Hu M, Chen H, Xie Q, Wang P, Li H, Peng J. Effectiveness of antiviral treatment in HBeAg-negative chronic hepatitis B patients with normal or mildly elevated alanine aminotransferase: a retrospective study. BMC Gastroenterol 2022; 22:387. [PMID: 35978283 PMCID: PMC9387004 DOI: 10.1186/s12876-022-02471-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Accepted: 08/09/2022] [Indexed: 11/29/2022] Open
Abstract
Background There are inadequate data and no histological evidence regarding the effects of antiviral treatment for hepatitis B e-antigen (HBeAg)-negative chronic hepatitis B (CHB) patients with normal or mildly elevated alanine aminotransferase (ALT). This study investigated the effects of antiviral treatment on these patients. Methods We retrospectively analysed the outcomes of antiviral treatment for HBeAg-negative CHB patients with normal or mildly elevated ALT who were treated with nucleoside/nucleotide analogues (NAs) for up to 96 weeks. Results A total of 128 patients were enrolled; 74 patients had normal ALT and 54 patients had mildly elevated ALT. The total cumulative rates of viral suppression were 64.06%, 81.97%, and 96.39%, at weeks 24, 48, and 96, respectively. The cumulative rates of viral suppression for the normal and mildly elevated ALT groups were 67.85% and 58.97%, 86.39% and 76.31%, and 93.13% and 97.04% at weeks 24, 48, and 96, respectively. The serum HBV DNA levels at week 12 and hepatitis B surface antigen (HBsAg) levels at week 24 were significant predictors of the 96-week virological response. Of the 128 patients, 54 with normal ALT and 33 with mildly elevated ALT underwent FibroScan at baseline. Significant fibrosis (F ≥ 2) was found in 44.4% (n = 24) and 51.5% (n = 17) of the patients in the normal ALT group and mildly elevated ALT group, respectively. Compared with the values at baseline, liver stiffness values significantly decreased at week 48 (8.12 kPa vs. 6.57 kPa; p < 0.001) and week 96 (8.87 kPa vs. 6.43 kPa; p < 0.001), respectively. Conclusions HBeAg-negative CHB patients with normal ALT could benefit from antiviral therapy with NAs, similar to patients with mildly elevated ALT. Antiviral treatment is strongly recommended for HBeAg-negative CHB patients with normal ALT. Additionally, significant liver fibrosis is not rare in HBeAg-negative CHB patients with ALT less than two-times the upper limit of normal, and FibroScan should be performed regularly for these patients. Supplementary Information The online version contains supplementary material available at 10.1186/s12876-022-02471-y.
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Affiliation(s)
- Sufang Wei
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510080, China
| | - Meixin Hu
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510080, China
| | - Hongjie Chen
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510080, China
| | - Qiuli Xie
- Department of Infectious Diseases, Shunde Hospital, Southern Medical University, Foshan, 528300, China
| | - Peng Wang
- Department of Infectious Diseases, Shunde Hospital, Southern Medical University, Foshan, 528300, China
| | - Hong Li
- Department of Infectious Diseases, Shunde Hospital, Southern Medical University, Foshan, 528300, China
| | - Jie Peng
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510080, China.
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Jang H, Lee YB, Moon H, Chung JW, Nam JY, Cho EJ, Lee JH, Yu SJ, Kim YJ, Lee J, Yoon JH. Aspirin use and risk of hepatocellular carcinoma in patients with chronic hepatitis B with or without cirrhosis. Hepatology 2022; 76:492-501. [PMID: 35100447 DOI: 10.1002/hep.32380] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 01/14/2022] [Accepted: 01/26/2022] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIMS Studies on differential effect of aspirin therapy on HCC risk across the spectrum of liver diseases are lacking. We investigated the association between aspirin use and risks of HCC, liver-associated death, and major bleeding in chronic hepatitis B (CHB) patients with or without cirrhosis. APPROACH AND RESULTS We identified 329,635 eligible adults with CHB from 2007 through 2017, using the Korean National Health Insurance Service database, including patients who received aspirin for ≥90 consecutive days (n = 20,200) and patients who never received antiplatelet therapy (n = 309,435). Risks of HCC, liver-associated mortality, and major bleeding were estimated in a propensity-score-matched cohort (19,003 pairs), accounting for competing risks. With a median follow-up of 6.7 years, 10-year cumulative incidence of HCC was 9.5% in the aspirin-treated group and 11.3% in the untreated group (adjusted subdistribution hazard ratio [aSHR], 0.85; 95% CI, 0.78-0.92). However, among patients with cirrhosis (2479 pairs), an association of aspirin use with HCC risk was not evident (aSHR, 1.00; 95% CI, 0.85-1.18). Cirrhosis status had a significant effect on the association between aspirin use and HCC risk (pinteraction , n = 0.04). Aspirin use was also associated with lower liver-associated mortality (aSHR, 0.80; 95% CI, 0.71-0.90). Moreover, aspirin use was not associated with major bleeding risk (aSHR, 1.09; 95% CI, 0.99-1.21). CONCLUSIONS Aspirin use was associated with reduced risks of HCC and liver-associated mortality in adults with CHB. Cirrhosis status had a substantial effect on the association between aspirin use and HCC risk.
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Affiliation(s)
- Heejoon Jang
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.,Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Republic of Korea
| | - Yun Bin Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Hyemi Moon
- Department of Biostatistics, College of Medicine, Korea University, Seoul, Republic of Korea
| | - Jong-Won Chung
- Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Joon Yeul Nam
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Eun Ju Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Su Jong Yu
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Yoon Jun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Juneyoung Lee
- Department of Biostatistics, College of Medicine, Korea University, Seoul, Republic of Korea
| | - Jung-Hwan Yoon
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
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Luo Z, Yao X, Li M, Fang D, Fei Y, Cheng Z, Xu Y, Zhu B. Modulating tumor physical microenvironment for fueling CAR-T cell therapy. Adv Drug Deliv Rev 2022; 185:114301. [PMID: 35439570 DOI: 10.1016/j.addr.2022.114301] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 04/07/2022] [Accepted: 04/12/2022] [Indexed: 02/06/2023]
Abstract
Chimeric antigen receptor (CAR) T cell therapy has achieved unprecedented clinical success against hematologic malignancies. However, the transition of CAR-T cell therapies for solid tumors is limited by heterogenous antigen expression, immunosuppressive microenvironment (TME), immune adaptation of tumor cells and impeded CAR-T-cell infiltration/transportation. Recent studies increasingly reveal that tumor physical microenvironment could affect various aspects of tumor biology and impose profound impacts on the antitumor efficacy of CAR-T therapy. In this review, we discuss the critical roles of four physical cues in solid tumors for regulating the immune responses of CAR-T cells, which include solid stress, interstitial fluid pressure, stiffness and microarchitecture. We highlight new strategies exploiting these features to enhance the therapeutic potency of CAR-T cells in solid tumors by correlating with the state-of-the-art technologies in this field. A perspective on the future directions for developing new CAR-T therapies for solid tumor treatment is also provided.
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KASL clinical practice guidelines for management of chronic hepatitis B. Clin Mol Hepatol 2022; 28:276-331. [PMID: 35430783 PMCID: PMC9013624 DOI: 10.3350/cmh.2022.0084] [Citation(s) in RCA: 54] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 04/01/2022] [Indexed: 01/10/2023] Open
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Sakamaki A, Takamura M, Sakai N, Watanabe Y, Arao Y, Kimura N, Setsu T, Abe H, Yokoo T, Kamimura H, Tsubata S, Waguri N, Ishikawa T, Kawai H, Sugitani S, Sato T, Funakoshi K, Watanabe M, Igarashi K, Kamimura K, Tsuchiya A, Aoyagi Y, Terai S. Longitudinal increase in albumin-bilirubin score is associated with non-malignancy-related mortality and quality of life in patients with liver cirrhosis. PLoS One 2022; 17:e0263464. [PMID: 35113969 PMCID: PMC8812983 DOI: 10.1371/journal.pone.0263464] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Accepted: 01/19/2022] [Indexed: 02/08/2023] Open
Abstract
Due to the developments in the treatment for hepatitis, it is possible to prevent the progression of liver fibrosis and improve patients’ prognosis even if it has already led to liver cirrhosis (LC). Consequently, a two-step study was conducted. To begin with, a retrospective study was conducted to identify the potential predictors of non-malignancy-related mortality from LC. Then, we prospectively analyzed the validity of these parameters as well as their association with patients’ quality of life. In the retrospective study, 89 cases were included, and the multivariate Cox regression analysis indicated that age (P = 0.012), model for end-stage liver disease (MELD) score (P = 0.012), and annual rate of change of the albumin–bilirubin (ALBI) score (P < 0.001) were significantly associated with LC prognosis. In the prospective study, 70 patients were included, and the patients were divided into cirrhosis progression and non-progression groups. The univariate logistic regression analysis indicated the serum procollagen type III N-terminal peptide level (P = 0.040) and MELD score (P = 0.010) were significantly associated with the annual rate of change of the ALBI score. Furthermore, the mean Chronic Liver Disease Questionnaire score worsened from 5.3 to 4.9 in the cirrhosis progression group (P = 0.034). In conclusion, a longitudinal increase in the ALBI score is closely associated with non-malignancy-related mortality and quality of life.
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Affiliation(s)
- Akira Sakamaki
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
- * E-mail:
| | - Masaaki Takamura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
- Division of Gastroenterology and Hepatology, JA Niigata Kouseiren Nagaoka Chuo General Hospital, Niigata, Japan
| | - Norihiro Sakai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Yusuke Watanabe
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
- Department of Preemptive Medicine for Digestive Diseases and Healthy Active Life, School of Medicine, Niigata University, Niigata, Japan
| | - Yoshihisa Arao
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Naruhiro Kimura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Toru Setsu
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Hiroyuki Abe
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Takeshi Yokoo
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
- Department of Preemptive Medicine for Digestive Diseases and Healthy Active Life, School of Medicine, Niigata University, Niigata, Japan
| | - Hiroteru Kamimura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Shunsuke Tsubata
- Department of Gastroenterology and Hepatology, Tachikawa General Hospital, Niigata, Japan
| | - Nobuo Waguri
- Department Gastroenterology and Hepatology, Niigata City General Hospital, Niigata, Japan
| | - Toru Ishikawa
- Division of Gastroenterology and Hepatology, Saiseikai Niigata Hospital, Niigata, Japan
| | - Hirokazu Kawai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
- Department of Internal Medicine, Niigata Prefectural Shibata Hospital, Niigata, Japan
| | - Soichi Sugitani
- Department of Gastroenterology and Hepatology, Tachikawa General Hospital, Niigata, Japan
- Department of Internal Medicine, Murakami General Hospital, Niigata, Japan
| | - Tomomi Sato
- Division of Gastroenterology and Hepatology, JA Niigata Kouseiren Nagaoka Chuo General Hospital, Niigata, Japan
- Department of Internal Medicine, Joetsu General Hospital, Niigata, Japan
| | - Kazuhiro Funakoshi
- Division of Gastroenterology and Hepatology, Niigata Prefectural Hospital, Niigata, Japan
| | - Masashi Watanabe
- Department of Internal Medicine, Niigata Prefectural Shibata Hospital, Niigata, Japan
| | - Kentarou Igarashi
- Department Gastroenterology and Hepatology, Niigata City General Hospital, Niigata, Japan
- Division of Gastroenterology and Hepatology, Mitsuke City Hospital, Niigata, Japan
| | - Kenya Kamimura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
- Department of General Medicine, School of Medicine, Niigata University, Niigata, Japan
| | - Atsunori Tsuchiya
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Yutaka Aoyagi
- Division of Gastroenterology and Hepatology, JA Niigata Medical Center, Niigata, Japan
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
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Hur M, Park M, Moon HW, Choe WH, Lee CH. Comparison of Non-Invasive Clinical Algorithms for Liver Fibrosis in Patients With Chronic Hepatitis B to Reduce the Need for Liver Biopsy: Application of Enhanced Liver Fibrosis and Mac-2 Binding Protein Glycosylation Isomer. Ann Lab Med 2022; 42:249-257. [PMID: 34635616 PMCID: PMC8548241 DOI: 10.3343/alm.2022.42.2.249] [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] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 08/20/2021] [Accepted: 09/10/2021] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Non-invasive clinical algorithms for the detection of liver fibrosis (LF) can reduce the need for liver biopsy (LB). We explored the implementation of two serum biomarkers, enhanced liver fibrosis (ELF) and Mac-2 binding protein glycosylation isomer (M2BPGi), in clinical algorithms for LF in chronic hepatitis B (CHB) patients. METHODS Two clinical algorithms were applied to 152 CHB patients: (1) transient elastography (TE) followed by biomarkers (TE/ELF and TE/M2GPGi); (2) biomarker test followed by TE (ELF/TE and M2BPGi/TE). Using the cut-off value or index for the detection of advanced LF (TE≥F3; 9.8 in ELF and 3.0 in M2BPGi), LB was expected to be performed in cases with discordant TE and biomarker results. RESULTS In both algorithms, the expected number of LBs was lower when using M2BPGi than when using ELF (TE/ELF or ELF/TE, 13.2% [N=20]; TE/M2BPGi or M2BPGi/TE, 9.9% [N=15]), although there was no statistical difference (P=0.398). In the TE low-risk group (TE≤F2), the discordance rate was significantly lower in the TE/M2BPGi approach than in the TE/ELF approach (1.5% [2/136] vs. 11.0% [15/136], P=0.002). In the biomarker low-risk group, there was no significant difference between the ELF/TE and M2BPGi/TE approaches (3.9% [5/126] vs. 8.8% [13/147], P=0.118). CONCLUSIONS Both ELF and M2BPGi can be implemented in non-invasive clinical algorithms for assessing LF in CHB patients. Given the lowest possibility of losing advanced LF cases in the low-risk group when using the TE/M2BPGi approach, this combination seems useful in clinical practice.
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Affiliation(s)
- Mina Hur
- Department of Laboratory Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Mikyoung Park
- Department of Laboratory Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | - Hee-Won Moon
- Department of Laboratory Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Won Hyeok Choe
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Chae Hoon Lee
- Department of Laboratory Medicine, Yeungnam University College of Medicine, Daegu, Korea
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20
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Kim MN, Ahn SH. Editorial: concurrent fatty liver and chronic viral hepatitis: a dual calamity leading to increased risk of hepatocellular carcinoma? Authors' reply. Aliment Pharmacol Ther 2022; 55:481-482. [PMID: 35092057 DOI: 10.1111/apt.16765] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2021] [Accepted: 12/28/2021] [Indexed: 12/09/2022]
Affiliation(s)
- Mi Na Kim
- Division of Gastroenterology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
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21
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Li T, Liu J, Wang Y, Zhou C, Shi Q, Huang S, Yang C, Chen Y, Bai Y, Xiong B. Liver fibrosis promotes immunity escape but limits the size of liver tumor in a rat orthotopic transplantation model. Sci Rep 2021; 11:22846. [PMID: 34819565 PMCID: PMC8613241 DOI: 10.1038/s41598-021-02155-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Accepted: 11/10/2021] [Indexed: 11/09/2022] Open
Abstract
Liver fibrosis plays a crucial role in promoting tumor immune escape and tumor aggressiveness for liver cancer. However, an interesting phenomenon is that the tumor size of liver cancer patients with liver fibrosis is smaller than that of patients without liver fibrosis. In this study, 16 SD rats were used to establish orthotopic liver tumor transplantation models with Walker-256 cell lines, respectively on the fibrotic liver (n = 8, LF group) and normal liver (n = 8, control group). MRI (magnetic resonance imaging) was used to monitor the size of the tumors. All rats were executed at the third week after modeling, and the immunohistochemical staining was used to reflect the changes in the tumor microenvironment. The results showed that, compared to the control group, the PD-L1 (programmed cell death protein receptor-L1) expression was higher, and the neutrophil infiltration increased while the effector (CD8+) T cell infiltration decreased in the LF group. Additionally, the expression of MMP-9 (matrix metalloproteinase-9) of tumor tissue in the LF group increased. Three weeks after modeling, the size of tumors in the LF group was significantly smaller than that in the control group (382.47 ± 195.06 mm3 vs. 1736.21 ± 657.25 mm3, P < 0.001). Taken together, we concluded that liver fibrosis facilitated tumor immunity escape but limited the expansion of tumor size.
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Affiliation(s)
- Tongqiang Li
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
| | - Jiacheng Liu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
| | - Yingliang Wang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
| | - Chen Zhou
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
| | - Qin Shi
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
| | - Songjiang Huang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
| | - Chongtu Yang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
| | - Yang Chen
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
| | - Yaowei Bai
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
| | - Bin Xiong
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022, China.
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China.
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22
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Roberts SK, Majeed A, Kemp W. Controversies in the Management of Hepatitis B: Hepatocellular Carcinoma. Clin Liver Dis 2021; 25:785-803. [PMID: 34593153 DOI: 10.1016/j.cld.2021.06.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Hepatitis B is the leading cause of hepatocellular cancer (HCC) worldwide. Untreated, annual HCC incidence rates in chronic hepatitis B subjects are 0.4% in noncirrhotics and 2% to 3% in cirrhotics. Surveillance with ultrasound with/without α-fetoprotein at 6-month intervals is recommended in at-risk persons including children. Antiviral therapy in chronic hepatitis B with entecavir or tenofovir significantly lowers the risk of HCC across all stages of liver disease, and lowers the risk of HCC recurrence following curative therapy. There are insufficient data to recommend use of tenofovir over entecavir in the prevention of de novo or recurrent HCC postcurative therapy.
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Affiliation(s)
- Stuart K Roberts
- The Alfred, 55 Commercial Road, Melbourne 3004, Australia; Monash University, Melbourne, Australia.
| | - Ammar Majeed
- The Alfred, 55 Commercial Road, Melbourne 3004, Australia; Monash University, Melbourne, Australia
| | - William Kemp
- The Alfred, 55 Commercial Road, Melbourne 3004, Australia; Monash University, Melbourne, Australia
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23
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Yoo SH, Lim TS, Lee HW, Kim JK, Lee JS, Lee HW, Kim BK, Park JY, Kim DY, Ahn SH, Lee JI, Lee KS, Kim SU. Risk assessment of hepatocellular carcinoma and liver-related events using ultrasonography and transient elastography in patients with chronic hepatitis B. J Viral Hepat 2021; 28:1362-1372. [PMID: 34185929 DOI: 10.1111/jvh.13560] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2021] [Accepted: 06/18/2021] [Indexed: 12/09/2022]
Abstract
Cirrhosis has prognostic value. We investigated whether the combined use of ultrasonography (US) and transient elastography (TE) to diagnose cirrhosis is beneficial for the risk assessment of hepatocellular carcinoma (HCC) and liver-related events in patients with chronic hepatitis B (CHB). A total of 9300 patients with CHB who underwent US and TE in two institutions between 2006 and 2018 were enrolled. TE value ≥13 kPa was set to indicate cirrhosis. Patients were divided into four groups: US(+)TE(+) (cirrhosis by US and TE), US(+)TE(-) (cirrhosis by US, but not by TE), US(-)TE(+) (cirrhosis by TE, but not by US) and US(-)TE(-) (non-cirrhosis by US and TE).The patients were predominantly male (n = 5474, 58.9%) with a mean age of 47.5 years. The proportions of patients with cirrhosis diagnosed by US and TE were 17.2% (n = 1595) and 13.2% (n = 1225), respectively. The proportion of patients with discordant results in diagnosing cirrhosis by US and TE was 18.7% (n = 1740). During follow-up (median: 60.0 months), HCC and liver-related events developed in 481 (5.2%) and 759 (8.2%) patients, respectively. The cumulative incidence rates of HCC and liver-related events were highest in the US(+)TE(+) group, intermediate-high in the US(-)TE(+) group, intermediate-low in the US(+)TE(-) group and lowest in the US(-)TE(-) group (overall p < .001). Cirrhosis assessed using US and TE was a major predictor of HCC and liver-related event development in patients with CHB. Cirrhosis assessed using TE seemed better in predicting HCC or liver-related events than using US, when cirrhosis diagnosis was discordant by US and TE.
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Affiliation(s)
- Sung Hwan Yoo
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.,Department of Internal Medicine, Gangnam Severance Hospital, Seoul, Republic of Korea
| | - Tae Seop Lim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.,Department of Internal Medicine, Yongin Severance Hospital, Yongin, Republic of Korea
| | - Hyun Woong Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.,Department of Internal Medicine, Gangnam Severance Hospital, Seoul, Republic of Korea
| | - Ja Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.,Department of Internal Medicine, Yongin Severance Hospital, Yongin, Republic of Korea
| | - Jae Seung Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.,Department of Internal Medicine, Severance Hospital, Seoul, Republic of Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.,Department of Internal Medicine, Severance Hospital, Seoul, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.,Department of Internal Medicine, Severance Hospital, Seoul, Republic of Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.,Department of Internal Medicine, Severance Hospital, Seoul, Republic of Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.,Department of Internal Medicine, Severance Hospital, Seoul, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.,Department of Internal Medicine, Severance Hospital, Seoul, Republic of Korea
| | - Jung Il Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.,Department of Internal Medicine, Gangnam Severance Hospital, Seoul, Republic of Korea
| | - Kwan Sik Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.,Department of Internal Medicine, Gangnam Severance Hospital, Seoul, Republic of Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.,Department of Internal Medicine, Severance Hospital, Seoul, Republic of Korea
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24
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Lee HW, Yip TCF, Tse YK, Wong GLH, Kim BK, Kim SU, Park JY, Kim DY, Chan HLY, Ahn SH, Wong VWS. Hepatic Decompensation in Cirrhotic Patients Receiving Antiviral Therapy for Chronic Hepatitis B. Clin Gastroenterol Hepatol 2021; 19:1950-1958.e7. [PMID: 32889148 DOI: 10.1016/j.cgh.2020.08.064] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Revised: 08/24/2020] [Accepted: 08/27/2020] [Indexed: 02/06/2023]
Abstract
OBJECTIVES It is unclear if anti-hepatitis B virus (HBV) treatment can eliminate incident hepatic decompensation. Here we report the incidence and predictors of hepatic decompensation among cirrhotic patients receiving antiviral therapy for chronic hepatitis B. METHODS This is a post hoc analysis of two prospective HBV cohorts from Hong Kong and South Korea. Patients with liver stiffness measurement (LSM) ≥10 kPa and compensated liver disease at baseline were included. The primary endpoint was incident hepatic decompensation (jaundice or cirrhotic complications) with competing risk analysis. RESULTS 818 patients (mean age, 54.9 years; 519 male [63.4%]) were included in the final analysis. During a mean follow-up of 58.1 months, 32 (3.9%) patients developed hepatic decompensation, among whom 34% were secondary to HCC. Three (0.4%) patients experienced variceal bleeding alone, 27 (3.3%) had non-bleeding decompensation and 13 (1.6%) had more than 2 decompensating events Baseline LSM, diabetes, alanine aminotransferase, platelet, total bilirubin, albumin, prothrombin time, and eGFR were independent predictors of hepatic decompensation. 30/506 (5.9%) patients fulfilling the Baveno VI criteria (LSM ≥20 kPa and/or platelet count <150ⅹ109/L) and 2/312 (0.6%) patients not fulfilling the criteria developed hepatic decompensation (P < .001). CONCLUSIONS Hepatic decompensation is uncommon but not eliminated in patients receiving antiviral therapy for HBV-related cirrhosis, and only a third of decompensating events are secondary to HCC. The Baveno VI criteria, which was originally designed to detect varices needing treatment, can be effectively applied in this population to identify patients at risk of decompensation.
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Affiliation(s)
- Hye Won Lee
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea; Insitute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea; Liver Center, Severance Hospital, Seoul, South Korea
| | - Terry Cheuk-Fung Yip
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Yee-Kit Tse
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Grace Lai-Hung Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea; Insitute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea; Liver Center, Severance Hospital, Seoul, South Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea; Insitute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea; Liver Center, Severance Hospital, Seoul, South Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea; Insitute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea; Liver Center, Severance Hospital, Seoul, South Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea; Insitute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea; Liver Center, Severance Hospital, Seoul, South Korea
| | - Henry Lik-Yuen Chan
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea; Insitute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea; Liver Center, Severance Hospital, Seoul, South Korea.
| | - Vincent Wai-Sun Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China.
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25
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Baglieri J, Zhang C, Liang S, Liu X, Nishio T, Rosenthal SB, Dhar D, Su H, Cong M, Jia J, Hosseini M, Karin M, Kisseleva T, Brenner DA. Nondegradable Collagen Increases Liver Fibrosis but Not Hepatocellular Carcinoma in Mice. THE AMERICAN JOURNAL OF PATHOLOGY 2021; 191:1564-1579. [PMID: 34119473 PMCID: PMC8406794 DOI: 10.1016/j.ajpath.2021.05.019] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Revised: 05/20/2021] [Accepted: 05/25/2021] [Indexed: 12/13/2022]
Abstract
Although hepatocellular cancer (HCC) usually occurs in the setting of liver fibrosis, the causal relationship between liver fibrosis and HCC is unclear. in vivo and in vitro models of HCC involving Colr/r mice (that produce a collagenase-resistant type I collagen) or wild-type (WT) mice were used to assess the relationship between type I collagen, liver fibrosis, and experimental HCC. HCC was either chemically induced in WT and Colr/r mice or Hepa 1-6 cells were engrafted into WT and Colr/r livers. The effect of hepatic stellate cells (HSCs) from WT and Colr/r mice on the growth of Hepa 1-6 cells was studied by using multicellular tumor spheroids and xenografts. Collagen type I deposition and fibrosis were increased in Colr/r mice, but they developed fewer and smaller tumors. Hepa 1-6 cells had reduced tumor growth in the livers of Colr/r mice. Although Colr/r HSCs exhibited a more activated phenotype, Hepa 1-6 growth and malignancy were suppressed in multicellular tumor spheroids and in xenografts containing Colr/r HSCs. Treatment with vitronectin, which mimics the presence of degraded collagen fragments, converted the Colr/r phenotype into a WT phenotype. Although Colr/r mice have increased liver fibrosis, they exhibited decreased HCC in several models. Thus, increased liver type I collagen does not produce increased experimental HCC.
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Affiliation(s)
- Jacopo Baglieri
- Department of Medicine, University of California San Diego, San Diego, California; Department of Surgery, University of California San Diego, San Diego, California
| | - Cuili Zhang
- Department of Medicine, University of California San Diego, San Diego, California
| | - Shuang Liang
- Department of Medicine, University of California San Diego, San Diego, California
| | - Xiao Liu
- Department of Medicine, University of California San Diego, San Diego, California
| | - Takahiro Nishio
- Department of Medicine, University of California San Diego, San Diego, California
| | - Sara B Rosenthal
- Center for Computational Biology and Bioinformatics, University of California San Diego, San Diego, California
| | - Debanjan Dhar
- Department of Medicine, University of California San Diego, San Diego, California
| | - Hua Su
- Department of Pharmacology, University of California San Diego, San Diego, California
| | - Min Cong
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis and National Clinical Research Center of Digestive Disease, Beijing, China
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis and National Clinical Research Center of Digestive Disease, Beijing, China
| | - Mojgan Hosseini
- Department of Pathology, University of California San Diego, San Diego, California
| | - Michael Karin
- Department of Pharmacology, University of California San Diego, San Diego, California
| | - Tatiana Kisseleva
- Department of Surgery, University of California San Diego, San Diego, California
| | - David A Brenner
- Department of Medicine, University of California San Diego, San Diego, California.
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26
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Zhang T, Zhang G, Deng X, Zeng J, Jin J, Zeping H, Wu M, Zheng R. APS (Age, Platelets, 2D Shear-Wave Elastography) Score Predicts Hepatocellular Carcinoma in Chronic Hepatitis B. Radiology 2021; 301:350-359. [PMID: 34427463 DOI: 10.1148/radiol.2021204700] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Background Two-dimensional (2D) shear-wave elastography (SWE) has been considered to be useful in predicting hepatocellular carcinoma (HCC) development in patients with chronic hepatitis B (CHB). Purpose To develop a risk model using 2D SWE to predict HCC in patients with CHB and to compare its predictive value with that of other models. Materials and Methods Patients with biopsy-proven CHB who underwent US and 2D SWE between April 2011 and December 2015 were enrolled in this study. After 2D SWE and biopsy were performed, the patients received regular follow-up for the detection of HCC. The scoring system was developed by dividing the parameters of the Cox proportional hazards model by the smallest parameter and simplifying the assigned points to integers. The predictive performance of the new score was compared with that of other scores. Results Among the 654 patients (mean age, 37 years; range, 30-43 years; 510 men), 26 developed HCC. The variables of age, platelet count, and liver stiffness measurement at 2D SWE were weighted to develop the so-called APS score, with a cutoff of 60 showing the best discrimination for HCC risk. The APS score (area under the receiver operating characteristic curve [AUC], 0.89) was superior to that of the Chinese University HCC prediction score constructed from age, albumin level, bilirubin level, hepatitis B virus (HBV) DNA level, and cirrhosis (AUC, 0.70; P = .005) and slightly higher than that of the guide with age, gender, HBV DNA level, core promoter mutations, and cirrhosis, or GAG-HCC score (AUC, 0.82; P = .052). In patients who underwent transient elastography, the AUC of the APS score was 0.79, compared with 0.82 for the modified risk estimation for HCC in CHB, or mREACH-B, score (P = .05). The APS score performed better in patients regardless of whether antiviral treatment was used, inflammation grade was low or high, or alanine aminotransferase levels were normal or high (all P > .05). Conclusion The APS score based on only the patient's baseline liver stiffness measurement at two-dimensional shear-wave elastography, age, and platelet count is valuable for predicting hepatocellular carcinoma in patients with chronic hepatitis B. © RSNA, 2021 Online supplemental material is available for this article.
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Affiliation(s)
- Ting Zhang
- From the Departments of Medical Ultrasonics (T.Z., J.Z., J.J., Z.H., M.W., R.Z.) and Infectious Disease (G.Z.), Third Affiliated Hospital of Sun Yat-Sen University, 600 TianHe Rd, Guangzhou 510630, China; and Department of Environmental Health Sciences, University at Albany, State University of New York, Rensselaer, NY (X.D.)
| | - Genglin Zhang
- From the Departments of Medical Ultrasonics (T.Z., J.Z., J.J., Z.H., M.W., R.Z.) and Infectious Disease (G.Z.), Third Affiliated Hospital of Sun Yat-Sen University, 600 TianHe Rd, Guangzhou 510630, China; and Department of Environmental Health Sciences, University at Albany, State University of New York, Rensselaer, NY (X.D.)
| | - Xinlei Deng
- From the Departments of Medical Ultrasonics (T.Z., J.Z., J.J., Z.H., M.W., R.Z.) and Infectious Disease (G.Z.), Third Affiliated Hospital of Sun Yat-Sen University, 600 TianHe Rd, Guangzhou 510630, China; and Department of Environmental Health Sciences, University at Albany, State University of New York, Rensselaer, NY (X.D.)
| | - Jie Zeng
- From the Departments of Medical Ultrasonics (T.Z., J.Z., J.J., Z.H., M.W., R.Z.) and Infectious Disease (G.Z.), Third Affiliated Hospital of Sun Yat-Sen University, 600 TianHe Rd, Guangzhou 510630, China; and Department of Environmental Health Sciences, University at Albany, State University of New York, Rensselaer, NY (X.D.)
| | - Jieyang Jin
- From the Departments of Medical Ultrasonics (T.Z., J.Z., J.J., Z.H., M.W., R.Z.) and Infectious Disease (G.Z.), Third Affiliated Hospital of Sun Yat-Sen University, 600 TianHe Rd, Guangzhou 510630, China; and Department of Environmental Health Sciences, University at Albany, State University of New York, Rensselaer, NY (X.D.)
| | - Huang Zeping
- From the Departments of Medical Ultrasonics (T.Z., J.Z., J.J., Z.H., M.W., R.Z.) and Infectious Disease (G.Z.), Third Affiliated Hospital of Sun Yat-Sen University, 600 TianHe Rd, Guangzhou 510630, China; and Department of Environmental Health Sciences, University at Albany, State University of New York, Rensselaer, NY (X.D.)
| | - Manli Wu
- From the Departments of Medical Ultrasonics (T.Z., J.Z., J.J., Z.H., M.W., R.Z.) and Infectious Disease (G.Z.), Third Affiliated Hospital of Sun Yat-Sen University, 600 TianHe Rd, Guangzhou 510630, China; and Department of Environmental Health Sciences, University at Albany, State University of New York, Rensselaer, NY (X.D.)
| | - Rongqin Zheng
- From the Departments of Medical Ultrasonics (T.Z., J.Z., J.J., Z.H., M.W., R.Z.) and Infectious Disease (G.Z.), Third Affiliated Hospital of Sun Yat-Sen University, 600 TianHe Rd, Guangzhou 510630, China; and Department of Environmental Health Sciences, University at Albany, State University of New York, Rensselaer, NY (X.D.)
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Impact of tenofovir alafenamide vs. entecavir on hepatocellular carcinoma risk in patients with chronic hepatitis B. Hepatol Int 2021; 15:1083-1092. [PMID: 34402025 DOI: 10.1007/s12072-021-10234-2] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Accepted: 07/04/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS Whether entecavir (ETV) or tenofovir alafenamide (TAF) is better at preventing hepatocellular carcinoma (HCC) development among patients with chronic hepatitis B (CHB) remains unclear. The present study was conducted to explore the ability of these two antivirals to prevent HCC. METHODS From 2012 to 2019, treatment-naïve CHB patients undergoing ETV or TAF therapy were recruited at three academic teaching hospitals. The TAF group comprised patients starting TAF as first-line antiviral and those switching antivirals from tenofovir disoproxil fumarate to TAF. Patients with decompensated cirrhosis or HCC at enrollment were excluded from the analysis. Cumulative probabilities of HCC were assessed using the Kaplan-Meier method. RESULTS In total, 1810 patients (1525 and 285 in ETV and TAF groups, respectively) were recruited. The annual HCC incidence was statistically not different between the ETV and TAF groups (1.67 vs. 1.19 per 100 person-years, respectively) with an adjusted hazard ratio (HR) of 0.681 (p = 0.255), as determined by multivariate analysis. Male, hypertension, liver cirrhosis, FIB-4 index, and albumin were independent prognostic factors for HCC development. Propensity score-matched and inverse probability of treatment weighting analyses yielded similar results, with non-statistically different HCC incidence between the ETV and TAF groups (1.07 vs. 1.19 per 100 person-years (HR = 0.973; p = 0.953) and 1.67 vs. 1.89 per 100 person-years, respectively (HR = 0.949; p = 0.743). CONCLUSIONS These findings suggest that ETV- and TAF-treated CHB patients have similar risk of developing HCC. Further studies with the larger sample size and longer follow-up are needed to validate these results.
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A Novel Orthotopic Liver Cancer Model for Creating a Human-like Tumor Microenvironment. Cancers (Basel) 2021; 13:cancers13163997. [PMID: 34439154 PMCID: PMC8394300 DOI: 10.3390/cancers13163997] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2021] [Revised: 08/04/2021] [Accepted: 08/05/2021] [Indexed: 12/11/2022] Open
Abstract
Simple Summary Hepatocellular carcinoma is the most common form of liver cancer. The lack of models that resemble actual tumor development in patients, limits the research to improve the diagnosis rate and develop new treatments. This study describes a novel mouse model that involves organoid formation and an implantation technique. This mouse model shares human genetic profiles and factors around the tumor, resembling the actual tumor development in patients. We demonstrate the roles of different cell types around the tumor, in promoting tumor growth, using this model. This model will be useful to understand the tumor developmental process, drug testing, diagnosis, prognosis, and treatment development. Abstract Hepatocellular carcinoma (HCC) is the most common form of liver cancer. This study aims to develop a new method to generate an HCC mouse model with a human tumor, and imitates the tumor microenvironment (TME) of clinical patients. Here, we have generated functional, three-dimensional sheet-like human HCC organoids in vitro, using luciferase-expressing Huh7 cells, human iPSC-derived endothelial cells (iPSC-EC), and human iPSC-derived mesenchymal cells (iPSC-MC). The HCC organoid, capped by ultra-purified alginate gel, was implanted into the disrupted liver using an ultrasonic homogenizer in the immune-deficient mouse, which improved the survival and engraftment rate. We successfully introduced different types of controllable TME into the model and studied the roles of TME in HCC tumor growth. The results showed the role of the iPSC-EC and iPSC-MC combination, especially the iPSC-MC, in promoting HCC growth. We also demonstrated that liver fibrosis could promote HCC tumor growth. However, it is not affected by non-alcoholic fatty liver disease. Furthermore, the implantation of HCC organoids to humanized mice demonstrated that the immune response is important in slowing down tumor growth at an early stage. In conclusion, we have created an HCC model that is useful for studying HCC development and developing new treatment options in the future.
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Dynamics of liver stiffness-based risk prediction model during antiviral therapy in patients with chronic hepatitis B. Eur J Gastroenterol Hepatol 2021; 33:885-893. [PMID: 32541238 DOI: 10.1097/meg.0000000000001794] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE The liver stiffness-based risk prediction models predict hepatocellular carcinoma (HCC) development. We investigated the influence of antiviral therapy (AVT) on liver stiffness-based risk prediction model in patients with chronic hepatitis B (CHB). METHODS Patients with CHB who initiated AVT were retrospectively recruited from 13 referral Korean institutes. The modified risk estimation for hepatocellular carcinoma in chronic hepatitis B (mREACH-B) model was selected for the analysis. RESULTS Between 2007 and 2015, 1034 patients with CHB were recruited. The mean age of the study population (639 men and 395 women) was 46.8 years. During AVT, the mREACH-B score significantly decreased from the baseline to 3 years of AVT (mean 9.21 → 7.46, P < 0.05) and was maintained until 5 years of AVT (mean 7.23, P > 0.05). The proportion of high-risk patients (mREACH-B score ≥11) was significantly reduced from the baseline to 2 years of AVT (36.4% → 16.4%, P < 0.001) and was maintained until 5 years of AVT (12.2%, P > 0.05). The mREACH-B scores at baseline and 1 year of AVT independently predicted HCC development (hazard ratio = 1.209-1.224) (all P < 0.05). The cumulative incidence rate of HCC was significantly different at 5 years of AVT among risk groups (high vs. high-intermediate vs. low-intermediate vs. low) from baseline (4.5% vs. 3.2% vs. 1.5% vs. 0.8%) and 1 year (11.8% vs. 4.6% vs. 1.8% vs. 0.6%) (all P < 0.05, log-rank tests). CONCLUSIONS The mREACH-B score was dynamically changed during AVT. Thus, repeated assessment of the mREACH-B score is required to predict the changing risk of HCC development in patients with CHB undergoing AVT.
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Ji JH, Park SY, Son WJ, Shin HJ, Lee H, Lee HW, Lee JS, Kim SU, Park JY, Kim DY, Ahn SH, Kim BK. External validation of CAGE-B and SAGE-B scores for Asian chronic hepatitis B patients with well-controlled viremia by antivirals. J Viral Hepat 2021; 28:951-958. [PMID: 33763928 DOI: 10.1111/jvh.13506] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 02/24/2021] [Accepted: 03/15/2021] [Indexed: 12/11/2022]
Abstract
CAGE-B and SAGE-B scores, consisting of age and fibrotic burden as cirrhosis and/or liver stiffness, were recently proposed to predict hepatocellular carcinoma (HCC) risk among Caucasian chronic hepatitis B (CHB) patients undergoing long-term antiviral therapy. We externally validated their predictive performances among an independent cohort from Asia, compared to other conventional prediction models. We consecutively recruited CHB patients with well-controlled viremia (serum HBV DNA < 2000 IU/mL) receiving antiviral therapy. Patients with decompensated cirrhosis or HCC at baseline were excluded. Among 1763 patients, CAGE-B score provided the highest Heagerty's integrated area under the curve (iAUC) (0.820), followed by SAGE-B (0.804), mREACH-B (0.800), CAMD (0.786), mPAGE-B (0.748) and PAGE-B (0.721) scores. CAGE-B score showed a significantly better performance than SAGE-B, CAMD, PAGE-B and mPAGE-B scores, but was similar to mREACH-B. SAGE-B score also showed significantly better performance than mPAGE-B and PAGE-B, but was similar to CAMD and mREACH-B. According to CAGE-B score 0-5, 6-10 and ≥11, the annual HCC incidences were 0.18, 1.34 and 6.03 per 100 person-years, respectively (all p < 0.001 between each pair). Likewise, by SAGE-B score 0-5, 6-10 and ≥11, those were 0.31, 1.49 and 8.96 per 100 person-years, respectively (all p < 0.001 between each pair). Hence, CAGE-B and SAGE-B scores showed acceptable predictive performances for Asian CHB patients undergoing antiviral therapy, with the higher performance by CAGE-B score. They show a trend towards better prognostic capability to predict HCC risk than previous models.
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Affiliation(s)
- Jung Hyun Ji
- Department of Internal medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Soo Young Park
- Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea
| | - Won Jeong Son
- Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Korea
| | - Hye Jung Shin
- Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Korea
| | - Hyein Lee
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea
| | - Hye Won Lee
- Department of Internal medicine, Yonsei University College of Medicine, Seoul, Korea.,Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea.,Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Seung Lee
- Department of Internal medicine, Yonsei University College of Medicine, Seoul, Korea.,Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea.,Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Seung Up Kim
- Department of Internal medicine, Yonsei University College of Medicine, Seoul, Korea.,Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea.,Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Jun Yong Park
- Department of Internal medicine, Yonsei University College of Medicine, Seoul, Korea.,Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea.,Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Do Young Kim
- Department of Internal medicine, Yonsei University College of Medicine, Seoul, Korea.,Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea.,Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Sang Hoon Ahn
- Department of Internal medicine, Yonsei University College of Medicine, Seoul, Korea.,Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea.,Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Beom Kyung Kim
- Department of Internal medicine, Yonsei University College of Medicine, Seoul, Korea.,Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea.,Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
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Lee HW, Lee HW, Lee JS, Roh YH, Lee H, Kim SU, Park JY, Kim DY, Ahn SH, Kim BK. The Prognostic Role of On-Treatment Liver Stiffness for Hepatocellular Carcinoma Development in Patients with Chronic Hepatitis B. J Hepatocell Carcinoma 2021; 8:467-476. [PMID: 34079776 PMCID: PMC8164698 DOI: 10.2147/jhc.s300382] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Accepted: 04/07/2021] [Indexed: 12/16/2022] Open
Abstract
Background Dynamic changes in fibrosis markers occur under long-term antiviral treatment (AVT) for chronic hepatitis B. We evaluated prognostic values of on-treatment liver stiffness (LS) compared to ultrasonography findings and determined its optimal cutoff. Methods The cumulative probability of hepatocellular carcinoma (HCC) was assessed among 880 patients receiving entecavir or tenofovir for ≥2 years. LS was measured using transient elastography. Results After ≥2 years’ AVT, the proportion of patients with cirrhosis on ultrasonography decreased from 54.7% to 44.9% and the mean LS decreased from 13.6 to 8.2 kPa (both p<0.001). However, unlike cirrhosis on ultrasonography before AVT (p<0.001), that after ≥2 years’ AVT did not discriminate HCC risk (p=0.792). Using the Contal and O’Quigley’s method, pre-AVT and on-treatment LS of 12.0 and 6.4 kPa, respectively, were chosen as optimal cutoffs to successfully discriminate HCC risk (both p<0.001). However, through stratification using both pre-AVT and on-treatment LS, the prognosis was finally determined according to on-treatment LS of 6.4 kPa, regardless of pre-AVT LS of 12.0 kPa. Using on-treatment LS of 12 kPa suggested by Caucasians with CHB receiving long-term AVT, patients with higher LS were more likely to develop HCC than those with lower LS (p=0.017); however, there was no significant difference between those with on-treatment LS of 6.4–11.9 and ≥ 12.0 kPa (p=0.920). Conclusion For HCC risk stratification in patients receiving long-term AVT, on-treatment LS cutoff should be lowered to 6.4 kPa, which is more predictive than 12 kPa or cirrhosis on ultrasonography. Further studies are required for validation.
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Affiliation(s)
- Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.,Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea.,Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Hyun Woong Lee
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jae Seung Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.,Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea.,Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Yun Ho Roh
- Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hyein Lee
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.,Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea.,Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.,Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea.,Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.,Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea.,Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.,Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea.,Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.,Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea.,Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
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Reig M, Forner A, Ávila MA, Ayuso C, Mínguez B, Varela M, Bilbao I, Bilbao JI, Burrel M, Bustamante J, Ferrer J, Gómez MÁ, Llovet JM, De la Mata M, Matilla A, Pardo F, Pastrana MA, Rodríguez-Perálvarez M, Tabernero J, Urbano J, Vera R, Sangro B, Bruix J. Diagnosis and treatment of hepatocellular carcinoma. Update of the consensus document of the AEEH, AEC, SEOM, SERAM, SERVEI, and SETH. Med Clin (Barc) 2021; 156:463.e1-463.e30. [PMID: 33461840 DOI: 10.1016/j.medcli.2020.09.022] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 09/12/2020] [Accepted: 09/15/2020] [Indexed: 12/12/2022]
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver neoplasm and one of the most common causes of death in patients with cirrhosis of the liver. In parallel, with recognition of the clinical relevance of this cancer, major new developments have recently appeared in its diagnosis, prognostic assessment and in particular, in its treatment. Therefore, the Spanish Association for the Study of the Liver (AEEH) has driven the need to update the clinical practice guidelines, once again inviting all the societies involved in the diagnosis and treatment of this disease to participate in the drafting and approval of the document: Spanish Society for Liver Transplantation (SETH), Spanish Society of Diagnostic Radiology (SERAM), Spanish Society of Vascular and Interventional Radiology (SERVEI), Spanish Association of Surgeons (AEC) and Spanish Society of Medical Oncology (SEOM). The clinical practice guidelines published in 2016 and accepted as National Health System Clinical Practice Guidelines were taken as the reference documents, incorporating the most important recent advances. The scientific evidence and the strength of the recommendation is based on the GRADE system.
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Affiliation(s)
- María Reig
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, IDIBAPS, Universidad de Barcelona, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España
| | - Alejandro Forner
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, IDIBAPS, Universidad de Barcelona, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España
| | - Matías A Ávila
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Programa de Hepatología, Centro de Investigación Médica Aplicada, Universidad de Navarra-IDISNA, Pamplona, España
| | - Carmen Ayuso
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Servicio de Radiodiagnóstico, Hospital Clínic Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Beatriz Mínguez
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Servicio de Hepatología, Hospital Universitario Vall d́Hebron, Grupo de Investigación en Enfermedades Hepáticas (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universidad Autónoma de Barcelona. Barcelona, España
| | - María Varela
- Sección de Hepatología, Servicio de Aparato Digestivo, Hospital Universitario Central de Asturias. Oviedo, España
| | - Itxarone Bilbao
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Servicio de Cirugía Hepatobiliopancreática y Trasplantes Digestivos, Hospital Universitario Vall d'Hebron, Universidad Autónoma de Barcelona. Barcelona, España
| | - José Ignacio Bilbao
- Unidad de Radiología Vascular e Intervencionista, Departamento de Radiodiagnóstico, Clínica Universidad de Navarra, Pamplona, España
| | - Marta Burrel
- Servicio de Radiodiagnóstico, Hospital Clínic Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Javier Bustamante
- Servicio de Gastroenterología y Hepatología, Sección de Hepatología y Trasplante, Hospital Universitario de Cruces, Baracaldo, España
| | - Joana Ferrer
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Cirugía Hepatobiliopancreática, Hospital Clínic, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Miguel Ángel Gómez
- Unidad de Cirugía Hepatobiliopancreática y Trasplantes, Hospital Universitario Virgen del Rocío, Sevilla, España
| | - Josep María Llovet
- Grupo de Investigación Traslacional en Oncología Hepática, Servicio de Hepatología, Hospital Clínic, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Manuel De la Mata
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Unidad Clínica de Aparato Digestivo, Hospital Universitario Reina Sofía, Córdoba, España
| | - Ana Matilla
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Sección de Hepatología, Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, Madrid, España
| | - Fernando Pardo
- Servicio de Cirugía Hepatobiliopancreática y Trasplante, Clínica Universidad de Navarra, Pamplona, España
| | - Miguel A Pastrana
- Servicio de Radiodiagnóstico, Hospital Universitario Puerta de Hierro, Universidad Autónoma de Madrid, Madrid, España
| | - Manuel Rodríguez-Perálvarez
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Unidad Clínica de Aparato Digestivo, Hospital Universitario Reina Sofía, Córdoba, España
| | - Josep Tabernero
- Servicio de Oncología Médica, Hospital Universitario Vall d'Hebron, Universidad Autónoma de Barcelona, Barcelona, España
| | - José Urbano
- Unidad de Radiología Vascular e Intervencionista, Servicio de Radiodiagnóstico, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Madrid, España
| | - Ruth Vera
- Servicio de Oncología Médica, Complejo hospitalario de Navarra, Navarrabiomed-IDISNA, Pamplona, España
| | - Bruno Sangro
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Unidad de Hepatología y Área de Oncología HBP, Clínica Universidad de Navarra-IDISNA, Pamplona, España.
| | - Jordi Bruix
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, IDIBAPS, Universidad de Barcelona, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España.
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Wu S, Xing X, Wang Y, Zhang X, Li M, Wang M, Wang Z, Chen J, Gao D, Zhao Y, Chen R, Ren Z, Zhang K, Cui J. The pathological significance of LOXL2 in pre-metastatic niche formation of HCC and its related molecular mechanism. Eur J Cancer 2021; 147:63-73. [PMID: 33618200 DOI: 10.1016/j.ejca.2021.01.011] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Revised: 12/22/2020] [Accepted: 01/07/2021] [Indexed: 02/07/2023]
Abstract
OBJECTIVE The mechanisms underlying the contribution of primary tumour to pre-metastatic niche formation remains largely unknown in hepatocellular carcinoma (HCC). We previously reported that the released LOXL2 from HCC cells under higher stiffness stimulation facilitated the formation of lung pre-metastatic niche. Here, we further clarified the pathological role of LOXL2 in promoting lung pre-metastatic niche formation and lung metastasis occurrence in HCC and its relevant molecular mechanism. METHODS Using two different animal models and an in vitro system of mechanically tuneable gel mirroring lung tissue stiffness, we explored the underlying mechanism of LOXL2 in pre-metastatic niche formation. RESULTS We applied tail vein injection of CM-LV-LOXL2-OEsimulating tumour-released soluble factors to induce lung pre-metastatic niche formation and found that the injected LOXL2 remarkably enhanced CD11b+/CD45+ bone marrow-derived cells (BMDCs) recruitment and fibronectin expression in lung. Subsequently, LOXL2-overexpressed xenograft HCC models validated that tumour-secreted LOXL2 significantly promoted the occurrence of pulmonary metastasis. In vitro, LOXL2 and LOXL2-caused matrix stiffening not only obviously upregulated the expressions of MMP9 and fibronectin in lung fibroblasts, but also evidently increased the number of adherent HCC cells and the expression of chemokine CXCL12. The activation of PI3K-AKT pathway mediated LOXL2-upregulated fibronectin. HCC patients in High-LOXL2 group had higher ratio of tumour recurrence than HCC patients in Low-LOXL2 group, supporting a significance of LOXL2 in HCC progression and unfavourable outcome. CONCLUSION Primary tumour-released LOXL2 promotes lung pre-metastatic niche formation and lung metastasis occurrence. LOXL2-caused matrix stiffening synergistically regulates lung pre-metastatic niche formation. Targeting LOXL2-induced lung pre-metastatic niche may be a novel intervention approach against HCC metastasis.
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Affiliation(s)
- Sifan Wu
- Liver Cancer Institute, Zhongshan Hospital, Fudan University & Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, 180 Feng Lin Road, Shanghai, 200032, PR China
| | - Xiaoxia Xing
- Liver Cancer Institute, Zhongshan Hospital, Fudan University & Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, 180 Feng Lin Road, Shanghai, 200032, PR China
| | - Yaohui Wang
- Department of Radiology, Shanghai Cancer Center, Fudan University, Shanghai, 200032, PR China
| | - Xi Zhang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University & Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, 180 Feng Lin Road, Shanghai, 200032, PR China
| | - Miao Li
- Liver Cancer Institute, Zhongshan Hospital, Fudan University & Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, 180 Feng Lin Road, Shanghai, 200032, PR China
| | - Mimi Wang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University & Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, 180 Feng Lin Road, Shanghai, 200032, PR China
| | - Zhiming Wang
- Department of Oncology, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China
| | - Jie Chen
- Liver Cancer Institute, Zhongshan Hospital, Fudan University & Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, 180 Feng Lin Road, Shanghai, 200032, PR China
| | - Dongmei Gao
- Liver Cancer Institute, Zhongshan Hospital, Fudan University & Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, 180 Feng Lin Road, Shanghai, 200032, PR China
| | - Yan Zhao
- Liver Cancer Institute, Zhongshan Hospital, Fudan University & Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, 180 Feng Lin Road, Shanghai, 200032, PR China
| | - Rongxin Chen
- Liver Cancer Institute, Zhongshan Hospital, Fudan University & Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, 180 Feng Lin Road, Shanghai, 200032, PR China
| | - Zhenggang Ren
- Liver Cancer Institute, Zhongshan Hospital, Fudan University & Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, 180 Feng Lin Road, Shanghai, 200032, PR China
| | - Kezhi Zhang
- Department of Hepatobiliary Surgery, Taizhou People's Hospital, Taizhou, 225300, Jiangsu Province, PR China.
| | - Jiefeng Cui
- Liver Cancer Institute, Zhongshan Hospital, Fudan University & Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, 180 Feng Lin Road, Shanghai, 200032, PR China.
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The Cook Score: A Novel Assessment for the Prediction of Liver-Associated Clinical Events in a Diverse Population. J Gastrointest Cancer 2021; 53:387-393. [PMID: 33683645 DOI: 10.1007/s12029-021-00620-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/01/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Transient elastography (TE) provides accurate quantification of liver fibrosis. Its usefulness could be significantly amplified in terms of predicting liver-associated clinical events (LACE). Our aim was to create a model that accurately predicts LACE by combining the information provided by TE with other variables in patients with chronic liver disease (CLD). METHODS We retrospectively reviewed the electronic medical records of patients who underwent liver elastography, at John H. Stroger Hospital in Cook County, Chicago, IL. The incidences of LACE were documented including decompensation of CLD, new hepatocellular carcinoma, and liver-associated mortality. Significant predicting factors were identified through a forward stepwise Cox regression model. We used the beta-coefficients of these risk factors to construct the Cook Score for prediction of LACE. Receiver-operating characteristic (ROC) curves were plotted for Cook Score to evaluate its efficiency in prediction, in comparison with MELD-Na Score and FIB-4 Score. RESULTS A total of 3097 patients underwent liver elastography at our institution. Eighty-eight LACE were identified. Age (hazard ratio (HR) 1.04, p = 0.002), aspartate aminotransferase to alanine aminotransferase ratio (HR 2.61, p < 0.001), platelet count (HR 0.98, p < 0.001), international normalized ration (INR) (HR 17.80, p < 0.001), and liver stiffness measurement (HR1.04, p < 0.001) were identified as significant predictors. The Cook Score was constructed with two optimal cut-off points to stratify patients into low-, intermediate-, and high-risk groups for LACE. The Cook Score proved superior than MELD-Na Score and FIB4 Score in predicting LACE with an area under curve of 0.828. CONCLUSION This novel score based on a large robust sample would provide accurate prediction of prognosis in patients with chronic liver disease and guide individualized surveillance strategy once validated with future studies.
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Sinharay R, Grant AJ, Rivett L, Blackwell R, Mells G, Gelson W. Assessing efficacy of hepatocellular carcinoma prediction scores to prioritise hepatitis B surveillance in the COVID-19 era. GASTROHEP 2021; 3:80-87. [PMID: 33821150 PMCID: PMC8014760 DOI: 10.1002/ygh2.443] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Accepted: 01/25/2021] [Indexed: 02/07/2023]
Abstract
OBJECTIVE An estimated 250 million people worldwide are chronically infected with hepatitis B virus (HBV), the leading cause of hepatocellular carcinoma (HCC) globally. The novel Sars-cov2 virus continues to spread at an alarming rate, and with guidance at the onset of the pandemic recommending the deferral of HCC surveillance, the implications on liver cancer care are now emerging and highlight the urgent need for reorganisation of services. METHODS We analysed how five HCC risk prediction scores could aid stratification of patients with chronic HBV. We calculated scores using parameters measured from 3 years prior (where available, n = 17) and at the time of HCC diagnosis in all adult patients with chronic HBV diagnosed with HCC (n = 46), and controls (n = 100). We compared the number of patients requiring cancer surveillance according to each score and regional surveillance guidance. RESULTS The aMAP score had the highest discriminatory performance in HCC risk prediction at 3 years (area under receiver-operating characteristic curve (auROC) of 0.824), followed by the mREACH B score (auROC of 0.719), and mPAGE B score (auROC of 0.742). However, only the mREACH B score had a negative predictive value (NPV) >99%. Applying the mREACH B score to our HBV cohort identified 11 patients requiring HCC surveillance, compared with 62 under current guidelines. CONCLUSION The use of HCC risk prediction scores could streamline the surveillance of patients with chronic HBV at a time of extremely limited resources. Overall, the mREACH B score had both a strong discriminatory performance and a high NPV, thus safely identifying low risk patients not requiring surveillance.
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Affiliation(s)
- Ricky Sinharay
- Department of PathologyUniversity of CambridgeCambridgeUK
- Cambridge Liver UnitCambridge University Hospitals NHS Foundation TrustCambridgeUK
| | | | - Lucy Rivett
- Department of Infectious DiseasesCambridge University NHS Hospitals Foundation TrustCambridgeUK
- Clinical Microbiology and Public Health LaboratoryPublic Health EnglandCambridgeUK
| | - Rebecca Blackwell
- Cambridge Liver UnitCambridge University Hospitals NHS Foundation TrustCambridgeUK
| | - George Mells
- Cambridge Liver UnitCambridge University Hospitals NHS Foundation TrustCambridgeUK
| | - William Gelson
- Cambridge Liver UnitCambridge University Hospitals NHS Foundation TrustCambridgeUK
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Fujimoto K, Shiinoki T, Yuasa Y, Tanaka H. Estimation of liver elasticity using the finite element method and four-dimensional computed tomography images as a biomarker of liver fibrosis. Med Phys 2021; 48:1286-1298. [PMID: 33449406 DOI: 10.1002/mp.14723] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Revised: 01/08/2021] [Accepted: 01/08/2021] [Indexed: 10/22/2022] Open
Abstract
PURPOSE Current radiotherapy planning procedures are generally designed based on anatomical information only and use computed tomography (CT) images that do not incorporate organ-functional information. In this study, we developed a method for estimating liver elasticity using the finite element method (FEM) and four-dimensional CT (4DCT) images acquired during radiotherapy planning, and we subsequently evaluated its feasibility as a biomarker for liver fibrosis. MATERIALS AND METHODS Twenty patients who underwent 4DCT and ultrasound-based transient elastography (UTE) were enrolled. All patients had chronic liver disease or cirrhosis. Liver elasticity measurements of the UTE were performed on the right lobe of the patient's liver in 20 patients. The serum biomarkers of the aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) were available in 18 of the 20 total patients, which were measured within 1 week after undergoing 4DCT. The displacement between the 4DCT images obtained at the endpoints of exhalation and inspiration was determined using the actual (via deformable image registration) and simulated (via FEM) respiration-induced displacement. The elasticity of each element of the liver model was optimized by minimizing the error between the actual and simulated respiration-induced displacement. Then, each patient's estimated liver elasticity was defined as the mean Young's modulus of the liver's right lobe and that of the whole liver using the estimated elasticity map. The estimated liver elasticity was evaluated for correlations with the elasticity obtained via UTE and with two serum biomarkers (APRI and FIB-4). RESULTS The mean ± standard deviation (SD) of the errors between the actual and simulated respiration-induced displacement in the liver model was 0.54 ± 0.33 mm. The estimated liver's right lobe elasticity was statistically significantly correlated with the UTE (r = 0.87, P < 0.001). Furthermore, the estimated whole liver elasticity was statistically significantly correlated with the UTE (r = 0.84, P < 0.001), APRI score (r = 0.62, P = 0.005), and FIB-4 score (r = 0.54, P = 0.021). CONCLUSION In this study, liver elasticity was estimated through FEM-based simulation and actual respiratory-induced liver displacement obtained from 4DCT images. Furthermore, we assessed that the estimated elasticity of the liver's right lobe was strongly correlated with the UTE. Therefore, the estimated elasticity has the potential to be a feasible imaging biomarker for assessing liver fibrosis using only 4DCT images without additional inspection or equipment costs. Because our results were derived from a limited sample of 20 patients, it is necessary to evaluate the accuracy of elasticity estimation for each liver segment on larger groups of biopsied patients to utilize liver elasticity information for radiotherapy planning.
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Affiliation(s)
- Koya Fujimoto
- Department of Radiation Oncology, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minamikogushi, Ube, Yamaguchi, 755-8535, Japan
| | - Takehiro Shiinoki
- Department of Radiation Oncology, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minamikogushi, Ube, Yamaguchi, 755-8535, Japan
| | - Yuki Yuasa
- Department of Radiation Oncology, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minamikogushi, Ube, Yamaguchi, 755-8535, Japan
| | - Hidekazu Tanaka
- Department of Radiation Oncology, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minamikogushi, Ube, Yamaguchi, 755-8535, Japan
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Wang R, Zang W, Hu B, Deng D, Ling X, Zhou H, Su M, Jiang J. Serum ESPL1 Can Be Used as a Biomarker for Patients With Hepatitis B Virus-Related Liver Cancer: A Chinese Case-Control Study. Technol Cancer Res Treat 2020; 19:1533033820980785. [PMID: 33308056 PMCID: PMC7739072 DOI: 10.1177/1533033820980785] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
AIMS To investigate the feasibility of serum extra spindle pole bodies-like 1 (ESPL1) used as a biomarker for patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS 131 chronic HBV-infection patients were recruited and divided into HBV S gene integration, non-HBV S gene integration, chronic hepatitis B (CHB), HBV-related liver cirrhosis (LC) and HBV-related HCC group, 24 non-HBV-related HCC patients were selected as HCC control group, 30 people without HBV-infection as healthy control group. Serum ESPL1 were detected and compared. RESULTS ESPL1 level of integration group was significantly higher than that of non-integration group (346.7 vs 199.6 ng/ml, P = 0.000) and healthy control group (346.7 vs 41.3 ng/ml, P = 0.000). ESPL1 level of non-integration group was significantly higher than that of healthy control group (199.6 vs 41.3 ng/ml, P = 0.000); ESPL1 levels in chronic HBV-infection related groups were increased in turn according to CHB group (95.8 ng/ml), HBV-related LC group (268.2 ng/ml), HBV-related HCC group (279.9 ng/ml) and integration group (346.7 ng/ml). Except that there was no significant difference in ESPL1 levels between HBV-related LC and HCC group (P = 0.662), pairwise comparisons between other groups showed significant differences (P < 0.05). ESPL1 level of HBV-related HCC group was significantly higher than that of non-HBV-related HCC group (279.9 vs 46.6 ng/ml, P = 0.000), there was no noticeable difference between non-HBV-related HCC and healthy control group (46.6 vs 41.3 ng/ml, P = 0.848). ESPL1 level of HBV-related HCC group after resection was significantly lower than that of before resection (178.4 vs 260.8 ng/ml, P = 0.000). CONCLUSIONS Chronic HBV-infection patients with high ESPL1 level may indicate HBV S gene integration and is a high-risk population for HBV-related HCC. Serum ESPL1 can be used as a biomarker for screening HBV-related HCC high-risk population and monitoring recurrence.
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Affiliation(s)
- Rongming Wang
- Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| | - Weiwei Zang
- Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| | - Bobin Hu
- Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| | - Deli Deng
- Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| | - Xiaozhang Ling
- Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| | - Huikun Zhou
- Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| | - Minghua Su
- Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| | - Jianning Jiang
- Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China
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Sakamaki A, Yokoyama K, Koyama K, Morita S, Abe H, Kamimura K, Takamura M, Terai S. Obesity and accumulation of subcutaneous adipose tissue are poor prognostic factors in patients with alcoholic liver cirrhosis. PLoS One 2020; 15:e0242582. [PMID: 33201936 PMCID: PMC7671528 DOI: 10.1371/journal.pone.0242582] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Accepted: 11/04/2020] [Indexed: 12/12/2022] Open
Abstract
In alcoholic liver cirrhosis (LC) patients, obesity has become a problem that progresses into liver dysfunction. Herein, we investigated the relationship between the prognosis of steatohepatitis and body weight, along with fat accumulation in patients with alcoholic LC. We conducted a single-center retrospective study, enrolled 104 alcoholic LC patients without hepatocellular carcinoma (HCC) based on histological and clinical evidence, and investigated factors related to poor prognosis using multivariate Cox regression and cluster analyses. Cox regression analysis revealed three independent relevant factors: subcutaneous adipose tissue (SAT) index (median 34.8 cm2/m2, P = 0.009, hazard ratio [HR] 1.017, 95% confidence interval [CI] 1.004-1.030), total bilirubin level (median 1.7 mg/dL, P = 0.003, HR 1.129, 95% CI 1.042-1.223), and prothrombin time value (median 64%, P = 0.007, HR 0.967, 95% CI 0.943-0.991). In the cluster analysis, we categorized the patients into three groups: no adipose tissue accumulation (NAT group), SAT prior accumulation (SAT group), and visceral adipose tissue prior accumulation (VAT group). The results of the three groups revealed that the SAT group displayed a significantly poor prognosis of the Kaplan-Meier curve (67.1 vs 21.2 vs 65.3, P<0.001) of a 5-year survival rate. Propensity score matching analysis of the SAT and VAT groups was performed to adjust the patient's background, but no significant differences were found between them; however, the prognosis was poorer (21.2 vs 66.3, P<0.001), and hemostatic factors were still at a lower level in the SAT group. These findings suggest that SAT accumulation type of obesity is a poor prognostic factor in alcoholic LC patients without HCC, and the hemorrhagic tendency might worsen the poor prognosis in such cases.
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Affiliation(s)
- Akira Sakamaki
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
- * E-mail:
| | - Kunihiko Yokoyama
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Kyutaro Koyama
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Shinichi Morita
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Hiroyuki Abe
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Kenya Kamimura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Masaaki Takamura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
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Zeng G, Gill US, Kennedy PTF. Prioritisation and the initiation of HCC surveillance in CHB patients: lessons to learn from the COVID-19 crisis. Gut 2020; 69:1907-1912. [PMID: 32451325 PMCID: PMC7295856 DOI: 10.1136/gutjnl-2020-321627] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Revised: 05/11/2020] [Accepted: 05/12/2020] [Indexed: 12/16/2022]
Affiliation(s)
- Georgia Zeng
- Faculty of Medicine, UNSW, Sydney, New South Wales, Australia
| | - Upkar S Gill
- Barts Liver Centre, Immunobiology, Blizard Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, London, UK
| | - Patrick T F Kennedy
- Barts Liver Centre, Immunobiology, Blizard Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, London, UK
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40
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Prognosis of Untreated Minimally Active Chronic Hepatitis B Patients in Comparison With Virological Responders by Antivirals. Clin Transl Gastroenterol 2020; 10:e00036. [PMID: 31107725 PMCID: PMC6613858 DOI: 10.14309/ctg.0000000000000036] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Serum hepatitis B virus (HBV)-DNA > 2,000 IU/mL is associated with higher risk of disease progression. However, without hepatocellular carcinoma (HCC) or cirrhosis, nucleos(t)ide analogs (NUCs) are recommended only for patients with elevated serum HBV-DNA and alanine aminotransferase ≥2 × upper normal limit.
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41
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Benmassaoud A, Nitulescu R, Pembroke T, Halme AS, Ghali P, Deschenes M, Wong P, Klein MB, Sebastiani G. Liver-related Events in Human Immunodeficiency Virus-infected Persons With Occult Cirrhosis. Clin Infect Dis 2020; 69:1422-1430. [PMID: 30561558 DOI: 10.1093/cid/ciy1082] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2018] [Accepted: 12/14/2018] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Human immunodeficiency virus (HIV)-infected patients are at increased risk of liver-related mortality. The effect of occult cirrhosis (OcC), defined as preclinical compensated cirrhosis without any clinical findings, on liver-related events is unknown. METHODS HIV-infected patients from 2 Canadian cohorts underwent transient elastography (TE) examination and were classified as (1) OcC (TE ≥13 kPa with no sign of cirrhosis, including absence of thrombocytopenia and signs of advanced liver disease on ultrasound or gastroscopy); (2) overt cirrhosis (OvC) (TE ≥13 kPa with signs of cirrhosis); or (3) noncirrhotic patients (TE <13 kPa). Incidence and risk factors of liver-related events were investigated through Kaplan-Meier and Cox regression analyses, respectively. We estimated monitoring rates according to screening guidelines for hepatocellular carcinoma (HCC) by OcC and OvC status. RESULTS A total of 1092 HIV-infected patients (51% coinfected with hepatitis C virus) were included. Prevalence of OcC and OvC at baseline was 2.7% and 10.7%, respectively. During a median follow-up of 1.8 (interquartile range, 1.5-2.8) years, the incidence of liver-related events in noncirrhosis, OcC, and OvC was 3.4 (95% confidence interval [CI], 1.2-7.3), 34.0 (95% CI, 6.0-104.0), and 37.0 (95% CI, 17.0-69.1) per 1000 person-years, respectively. Baseline OcC (adjusted hazard ratio [aHR], 7.1 [95% CI, 1.3-38.0]) and OvC (aHR, 8.5 [95% CI, 2.8-26.0]) were independently associated with liver-related events. Monitoring rates for HCC were lower in patients with OcC (24%) compared to those with OvC (40%). CONCLUSIONS HIV-infected patients with OcC have a high incidence of liver-related events. Greater surveillance and earlier recognition with appropriate screening strategies are necessary for improved outcomes.
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Affiliation(s)
- Amine Benmassaoud
- Division of Gastroenterology and Hepatology, Royal Victoria Hospital
| | - Roy Nitulescu
- Chronic Viral Illness Service, McGill University Health Centre, Montreal, Canada
| | - Thomas Pembroke
- Division of Gastroenterology and Hepatology, Royal Victoria Hospital.,Department of Infection and Immunity, Cardiff University, United Kingdom
| | - Alex S Halme
- Division of Gastroenterology and Hepatology, Royal Victoria Hospital
| | - Peter Ghali
- Division of Gastroenterology and Hepatology, Royal Victoria Hospital
| | - Marc Deschenes
- Division of Gastroenterology and Hepatology, Royal Victoria Hospital
| | - Philip Wong
- Division of Gastroenterology and Hepatology, Royal Victoria Hospital
| | - Marina B Klein
- Chronic Viral Illness Service, McGill University Health Centre, Montreal, Canada
| | - Giada Sebastiani
- Division of Gastroenterology and Hepatology, Royal Victoria Hospital.,Chronic Viral Illness Service, McGill University Health Centre, Montreal, Canada
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Yim HJ, Kim JH, Park JY, Yoon EL, Park H, Kwon JH, Sinn DH, Lee SH, Lee JH, Lee HW. Comparison of clinical practice guidelines for the management of chronic hepatitis B: When to start, when to change, and when to stop. Clin Mol Hepatol 2020; 26:411-429. [PMID: 32854458 PMCID: PMC7641563 DOI: 10.3350/cmh.2020.0049] [Citation(s) in RCA: 69] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Accepted: 06/21/2020] [Indexed: 02/06/2023] Open
Abstract
Clinical practice guidelines are important for guiding the management of specific diseases by medical practitioners, trainees, and nurses. In some cases, the guidelines are utilized as a reference for health policymakers in controlling diseases with a large public impact. With this in mind, practice guidelines for the management of chronic hepatitis B (CHB) have been developed in the United States, Europe, and Asian-Pacific regions to suggest the best-fit recommendations for each social and medical circumstance. Recently, the Korean Association for the Study of the Liver published a revised version of its clinical practice guidelines for the management of CHB. The guidelines included updated information based on newly available antiviral agents, the most recent opinion on the initiation and cessation of treatment, and updates for the management of drug resistance, partial virological response, and side effects. Additionally, CHB management in specific situations was comprehensively revised. This review compares the similarities and differences among the various practice guidelines to identify unmet needs and improve future recommendations.
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Affiliation(s)
- Hyung Joon Yim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Ji Hoon Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Eileen L Yoon
- Department of Internal Medicine, Inje University College of Medicine, Seoul, Korea
| | - Hana Park
- Department of Health Medicine, Asan Medical Center, Seoul, Korea
| | - Jung Hyun Kwon
- Department of Internal Medicine, College of Medicine, the Catholic University of Korea, Seoul, Korea
| | - Dong Hyun Sinn
- Department of Internal Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sae Hwan Lee
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Chonan, Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Hyun Woong Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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Abstract
Chronic liver injury due to viral hepatitis, alcohol abuse, and metabolic disorders is a worldwide health concern. Insufficient treatment of chronic liver injury leads to fibrosis, causing liver dysfunction and carcinogenesis. Most cases of hepatocellular carcinoma (HCC) develop in the fibrotic liver. Pathological features of liver fibrosis include extracellular matrix (ECM) accumulation, mesenchymal cell activation, immune deregulation, and angiogenesis, all of which contribute to the precancerous environment, supporting tumor development. Among liver cells, hepatic stellate cells (HSCs) and macrophages play critical roles in fibrosis and HCC. These two cell types interplay and remodel the ECM and immune microenvironment in the fibrotic liver. Once HCC develops, HCC-derived factors influence HSCs and macrophages to switch to protumorigenic cell populations, cancer-associated fibroblasts and tumor-associated macrophages, respectively. This review aims to summarize currently available data on the roles of HSCs and macrophages in liver fibrosis and HCC, with a focus on their interaction.
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Affiliation(s)
- Michitaka Matsuda
- Division of Digestive and Liver Diseases, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California
| | - Ekihiro Seki
- Division of Digestive and Liver Diseases, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California
- Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California
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44
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Lee HW, Park SY, Lee M, Lee EJ, Lee J, Kim SU, Park JY, Kim DY, Ahn SH, Kim BK. An optimized hepatocellular carcinoma prediction model for chronic hepatitis B with well-controlled viremia. Liver Int 2020; 40:1736-1743. [PMID: 32239602 DOI: 10.1111/liv.14451] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2019] [Revised: 03/04/2020] [Accepted: 03/17/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Hepatocellular carcinoma (HCC) risk in chronic hepatitis B (CHB) substantially decreased in the era of potent antiviral therapy. We developed an optimized HCC risk prediction model for CHB with well-controlled viremia by nucelos(t)ide analogs (NUCs). METHOD We analysed those who achieved virological response (VR; serum HBV-DNA < 2000 IU/mL on two consecutive assessments) by NUCs. Liver stiffness by transient elastography, ultrasonography and laboratory tests was performed at the time of confirmed VR. Patients with decompensated cirrhosis or HCC at baseline were excluded. Multivariate Cox-regression analysis was used to determine key variables to construct a novel risk-scoring model. RESULTS Among 1511 patients, 9.5% developed HCC. Cirrhosis on ultrasonography (adjusted HR [aHR] 2.47), age (aHR 1.04), male (aHR 1.90), platelet count <135 000/uL (aHR 1.57), albumin <4.5 g/dL (aHR 1.77) and liver stiffness ≥11 kPa (aHR 6.09) were independently associated with HCC. Using these, CAMPAS model was developed with c-index of 0.874. The predicted and observed HCC probabilities were calibrated with a reliable agreement. Such results were reproduced from internal validation and external validation among the independent cohort (n = 252). The intermediate-risk (CAMPAS model score 75 ~ 161) and high-risk (score >161) groups were more likely to develop HCC compared with the low-risk group (score ≤75) with statistical significances (HRs; 4.43 and 47.693 respectively; both P < .001). CONCLUSION CAMPAS model derived through comprehensive clinical evaluation of liver disease allowed the more delicate HCC prediction for CHB patients with well-controlled viremia by NUCs.
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Affiliation(s)
- Hye W Lee
- Department of Internal medicine, Yonsei University College of medicine, Seoul, Republic of Korea.,Institute of Gastroenterology, Yonsei University College of medicine, Seoul, Republic of Korea.,Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Soo Y Park
- Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Myeongjee Lee
- Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Eun J Lee
- Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jinae Lee
- Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Seung U Kim
- Department of Internal medicine, Yonsei University College of medicine, Seoul, Republic of Korea.,Institute of Gastroenterology, Yonsei University College of medicine, Seoul, Republic of Korea.,Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Jun Y Park
- Department of Internal medicine, Yonsei University College of medicine, Seoul, Republic of Korea.,Institute of Gastroenterology, Yonsei University College of medicine, Seoul, Republic of Korea.,Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Do Y Kim
- Department of Internal medicine, Yonsei University College of medicine, Seoul, Republic of Korea.,Institute of Gastroenterology, Yonsei University College of medicine, Seoul, Republic of Korea.,Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Sang H Ahn
- Department of Internal medicine, Yonsei University College of medicine, Seoul, Republic of Korea.,Institute of Gastroenterology, Yonsei University College of medicine, Seoul, Republic of Korea.,Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Beom K Kim
- Department of Internal medicine, Yonsei University College of medicine, Seoul, Republic of Korea.,Institute of Gastroenterology, Yonsei University College of medicine, Seoul, Republic of Korea.,Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
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Marasco G, Colecchia A, Silva G, Rossini B, Eusebi LH, Ravaioli F, Dajti E, Alemanni LV, Colecchia L, Renzulli M, Golfieri R, Festi D. Non-invasive tests for the prediction of primary hepatocellular carcinoma. World J Gastroenterol 2020; 26:3326-3343. [PMID: 32655261 PMCID: PMC7327793 DOI: 10.3748/wjg.v26.i24.3326] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Revised: 04/08/2020] [Accepted: 06/12/2020] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world and it is one of the main complications of cirrhosis and portal hypertension. Even in the presence of a well-established follow-up protocol for cirrhotic patients, to date poor data are available on predictive markers for primary HCC occurrence in the setting of compensated advanced chronic liver disease patients (cACLD). The gold standard method to evaluate the prognosis of patients with cACLD, beyond liver fibrosis assessed with histology, is the measurement of the hepatic venous pressure gradient (HVPG). An HVPG ≥10 mmHg has been related to an increased risk of HCC in cACLD patients. However, these methods are burdened by additional costs and risks for patients and are mostly available only in referral centers. In the last decade increasing research has focused on the evaluation of several, simple, non-invasive tests (NITs) as predictors of HCC development. We reviewed the currently available literature on biochemical and ultrasound-based scores developed for the non-invasive evaluation of liver fibrosis and portal hypertension in predicting primary HCC. We found that the most reliable methods to assess HCC risk were the liver stiffness measurement, the aspartate aminotransferase to platelet ratio index score and the fibrosis-4 index. Other promising NITs need further investigations and validation for different liver disease aetiologies.
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Affiliation(s)
- Giovanni Marasco
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna 40138, Italy
| | - Antonio Colecchia
- Unit of Gastroenterology, Borgo Trento University Hospital of Verona, Verona 37126, Italy
| | - Giovanni Silva
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna 40138, Italy
| | - Benedetta Rossini
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna 40138, Italy
| | - Leonardo Henry Eusebi
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna 40138, Italy
| | - Federico Ravaioli
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna 40138, Italy
| | - Elton Dajti
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna 40138, Italy
| | - Luigina Vanessa Alemanni
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna 40138, Italy
| | - Luigi Colecchia
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna 40138, Italy
| | - Matteo Renzulli
- Radiology Unit, Sant’Orsola Malpighi Hospital, University of Bologna, Bologna 40138, Italy
| | - Rita Golfieri
- Radiology Unit, Sant’Orsola Malpighi Hospital, University of Bologna, Bologna 40138, Italy
| | - Davide Festi
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna 40138, Italy
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Joo I, Kim SY, Park HS, Lee ES, Kang HJ, Lee JM. Validation of a New Point Shear-Wave Elastography Method for Noninvasive Assessment of Liver Fibrosis: A Prospective Multicenter Study. Korean J Radiol 2020; 20:1527-1535. [PMID: 31606957 PMCID: PMC6791814 DOI: 10.3348/kjr.2019.0109] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2019] [Accepted: 07/15/2019] [Indexed: 12/18/2022] Open
Abstract
Objective To validate the diagnostic value of a new point shear-wave elastography method, S-shearwave elastography (S-SWE; Samsung Medison Co., Ltd.), in noninvasive assessment of liver fibrosis. Materials and Methods In this prospective multicenter study, liver stiffness (LS) measurements for 600 participants were obtained with both S-SWE and transient elastography (TE). The rates of unsuccessful LS measurements in S-SWE and TE were compared, and correlations between S-SWE and TE measurements were assessed. In 107 patients with histologic reference data, the optimal LS cut-off values for predicting severe fibrosis and cirrhosis on S-SWE were determined using receiver operating characteristic (ROC) curve analysis. The LS cut-off values in S-SWE were then validated in 463 patients without histologic reference data by using TE values as the reference standard, and the sensitivity and specificity of the cut-off values for predicting severe fibrosis and cirrhosis were calculated. Results The frequency of unsuccessful LS measurements on TE (4.5%, 27/600) was significantly higher than that (0.7%, 4/600) on S-SWE (p < 0.001). LS measurements on S-SWE showed a significant correlation with TE values (r = 0.880, p < 0.001). In 107 patients with histological reference data, the areas under the ROC curves on S-SWE were 0.845 and 0.850, with optimal cut-offs of 7.0 kilopascals (kPa) and 9.7 kPa, for the diagnosis of severe fibrosis and cirrhosis, respectively. Using these cut-off values, S-SWE showed sensitivities of 92.9% and 97.4% and specificities of 89.5% and 83.1% in TE-based evaluations of severe fibrosis and cirrhosis, respectively. Conclusion LS measurements on S-SWE were well correlated with those on TE. In addition, S-SWE provided good diagnostic performance for staging of hepatic fibrosis, with a lower rate of unsuccessful LS measurements compared with TE.
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Affiliation(s)
- Ijin Joo
- Department of Radiology, Seoul National University Hospital and Seoul National College of Medicine, Seoul, Korea
| | - So Yeon Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
| | - Hee Sun Park
- Department of Radiology, Konkuk University School of Medicine, Seoul, Korea
| | - Eun Sun Lee
- Department of Radiology, Chung-Ang University Hospital, Seoul, Korea
| | - Hyo Jeong Kang
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Jeong Min Lee
- Department of Radiology, Seoul National University Hospital and Seoul National College of Medicine, Seoul, Korea
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Sinn DH. [Natural History and Treatment Indications of Chronic Hepatitis B]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2020; 74:245-250. [PMID: 31765552 DOI: 10.4166/kjg.2019.74.5.245] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/12/2019] [Revised: 10/27/2019] [Accepted: 10/28/2019] [Indexed: 12/21/2022]
Abstract
HBV is the most common etiology of both liver cirrhosis and hepatocellular carcinoma in Korea. Despite much progress made, the currently available antiviral therapies cannot eradicate or eliminate this virus. Hence, the benefits and risks of antiviral therapy should be carefully evaluated on an individual basis and within the context of the clinical situation. The ultimate goals of treatment are to decrease the mortality from liver disease. The benefits of antiviral therapy come from prevention of progression of liver disease. Understanding the natural history of chronic HBV infection is a key step in the decision making process to treat patients with chronic HBV infection. Generally, chronic hepatitis B patients in the immune tolerant phase and immune inactive phase are not recommended to undergo antiviral treatment, except for those patients in special conditions (e.g., immunosuppression or anticancer chemotherapy). Chronic hepatitis B patients in the immune active phase are recommended for antiviral therapy. For patients with liver cirrhosis, treatment should be considered when serum HBV DNA is detectable regardless of the serum level of ALT.
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Affiliation(s)
- Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Fibrosis-4, aspartate transaminase-to-platelet ratio index, and gamma-glutamyl transpeptidase-to-platelet ratio for risk assessment of hepatocellular carcinoma in chronic hepatitis B patients: comparison with liver biopsy. Eur J Gastroenterol Hepatol 2020; 32:433-439. [PMID: 31490417 DOI: 10.1097/meg.0000000000001520] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS It is well known that hepatocellular carcinoma (HCC) develops as a consequence of hepatic fibrosis progression. Thus, early identification of advanced liver fibrosis is very important. This study evaluated the prognostic value of FIB-4, the aspartate transaminase to-platelet ratio index (APRI), and the gamma-glutamyl transpeptidase-toplatelet ratio (GPR) for predicting HCC development using histological fibrosis stage as a reference in Asian chronic hepatitis B (CHB) patients. METHODS A total of 444 CHB patients who underwent liver biopsy and serological tests for determining noninvasive serum fibrosis markers were enrolled. All patients were followed to monitor HCC development. RESULTS The histological fibrosis stage showed best performance in predicting HCC development at 5 (area under the receiver operating characteristic curve [AUROC] = 0.783) and 7 years (AUROC = 0.766), followed by FIB-4 (AUROC = 0.753 at 5 years, 0.698 at 7 years), APRI (AUROC = 0.658 at 5 years, 0.572 at 7 years), and GPR (AUROC = 0.638 at 5 years, 0.603 at 7 years). When we classified risk groups according to the histological fibrosis stage (F4 vs. F0-3) and FIB-4 (FIB-4 ≥ 3.25 vs. FIB-4 < 3.25), patients in the high-risk group were found to have a significantly higher probability of developing HCC than those in the low-risk group (P=0.005 and 0.022, respectively, log-rank test). CONCLUSION Our study demonstrated that FIB-4 is useful for the noninvasive prediction of HCC development, while APRI and GPR were less useful.
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Kim SU, Seo YS, Lee HA, Kim MN, Kim EH, Kim HY, Lee YR, Lee HW, Park JY, Kim DY, Ahn SH, Han KH, Hwang SG, Rim KS, Um SH, Tak WY, Kweon YO, Kim BK, Park SY. Validation of the CAMD Score in Patients With Chronic Hepatitis B Virus Infection Receiving Antiviral Therapy. Clin Gastroenterol Hepatol 2020; 18:693-699.e1. [PMID: 31252188 DOI: 10.1016/j.cgh.2019.06.028] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2019] [Revised: 05/29/2019] [Accepted: 06/16/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Researchers previously developed a scoring system to determine the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection, based on the presence of cirrhosis, patient age, male sex, and diabetes (called the CAMD scoring system). We validated the CAMD scoring system and compared its performance with that of other risk assessment models in an independent cohort. METHODS We followed up 3277 patients with chronic HBV infection (mean age, 48.7 y; 62.6% male; 32.4% with cirrhosis) who were treated with entecavir (n = 1725) or tenofovir (n = 1552) as the first-line antiviral agent in 4 academic teaching hospitals in the Republic of Korea. The primary outcome was development of HCC. We evaluated the ability of the CAMD, PAGE-B, and mPAGE-B scoring systems to identify patients who would develop HCC using integrated area under the curve (iAUC) analysis. RESULTS Over a median follow-up period of 58.2 months, 8.9% of the patients developed HCC. Patients who developed HCC were older, more likely to be male, and had higher proportions of cirrhosis and diabetes than patients who did not develop HCC (all P < .05). CAMD scores identified patients who developed HCC with an iAUC of 0.790, mPAGE-B scores with an iAUC of 0.769, and PAGE-B scores with an iAUC of 0.760. The 5-year cumulative risks of HCC were 1.3% in patients with low CAMD scores (<8), 8.0% in patients with intermediate CAMD scores (8-13), and 24.3% in patients with high CAMD scores (>13) (P < .001 for comparison of low- vs intermediate-score groups and between intermediate- vs high-score groups). The predicted and observed probabilities of HCC had excellent agreement. CONCLUSIONS We validated the CAMD scoring system in determining the risk of HCC in patients with chronic HBV treatment receiving entecavir or tenofovir treatment. Validation was performed in a cohort of patients in the Republic of Korea, where most patients have genotype C2 HBV infection.
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Affiliation(s)
- Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea; Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Yeon Seok Seo
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Han Ah Lee
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Mi Na Kim
- Department of Internal Medicine, CHA Bundang Medical Center, Cha University, Seongnam, Republic of Korea
| | - Eun Hwa Kim
- Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Ha Yan Kim
- Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yu Rim Lee
- Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea; Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea; Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea; Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Kwang-Hyub Han
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea; Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Seong Gyu Hwang
- Department of Internal Medicine, CHA Bundang Medical Center, Cha University, Seongnam, Republic of Korea
| | - Kyu Sung Rim
- Department of Internal Medicine, CHA Bundang Medical Center, Cha University, Seongnam, Republic of Korea
| | - Soon Ho Um
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Won Young Tak
- Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Young Oh Kweon
- Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea; Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea.
| | - Soo Young Park
- Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea.
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Sarcopenia assessed using bioimpedance analysis is associated independently with significant liver fibrosis in patients with chronic liver diseases. Eur J Gastroenterol Hepatol 2020; 32:58-65. [PMID: 31283527 DOI: 10.1097/meg.0000000000001475] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
AIM Sarcopenia is common in patients with advanced fibrosis or cirrhosis. We investigated the correlation between sarcopenia and other clinical variables, in particular, significant liver fibrosis in patients with chronic liver diseases (CLDs). PATIENTS AND METHODS Patients with CLDs who underwent transient elastography (TE) and bioelectrical impedance analysis between 2015 and 2017 were retrospectively recruited. The sarcopenia index (SI) was calculated as follows: SI = total appendicular skeletal muscle mass (kg)/ body mass index (BMI) (kg/m). Sarcopenia was defined as SI less than 0.789 for men and less than 0.521 for women. Significant liver fibrosis and fatty liver were defined using TE liver stiffness value more than 7 kPa and controlled attenuation parameter more than 250 dB/m, respectively. RESULTS Of 2168 patients recruited, 218 (10.1%) had sarcopenia. Age, BMI, diabetes, hypertension, fasting glucose, aspartate aminotransferase, and liver stiffness value were correlated positively with sarcopenia (all P < 0.05), whereas male sex, viral etiology, obesity (BMI > 25 kg/m), total bilirubin, and serum albumin were correlated negatively with sarcopenia (all P < 0.05). On multivariate analysis, TE-defined significant liver fibrosis was associated independently with sarcopenia (odds ratio = 1.597; 95% confidence interval: 1.174-2.172; P = 0.003), together with age, male sex, viral etiology, and TE-defined fatty liver (all P < 0.05). Among the subgroups with ultrasonography-defined nonalcoholic fatty liver disease (n = 957), sarcopenia was also associated independently with TE-defined significant liver fibrosis (odds ratio = 1.887; 95% confidence interval: 1.261-2.823; P < 0.001). CONCLUSION Sarcopenia is associated independently with significant liver fibrosis in patients with CLDs. Further studies are required to determine whether interventions to improve muscle mass can improve liver fibrosis.
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