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He MW, Cui L, Chen DD, Zhao Y, Luo WZ, Jia YF, Zhou J, He QJ, Dai Y, Zhang WH, Yu ZX, Wang WC, Guo C, Fu YM, Yang WC, Li XY, Guo YF, Wang CY, Wang JJ, Li P, Qiao B, Ji D, Li ZB. Efficacy and safety of switching from entecavir to tenofovir alafenamide in chronic hepatitis B patients with low-level viremia: a real-world 48-week extension study. Antimicrob Agents Chemother 2025; 69:e0182724. [PMID: 39902928 PMCID: PMC11881556 DOI: 10.1128/aac.01827-24] [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: 12/06/2024] [Accepted: 01/11/2025] [Indexed: 02/06/2025] Open
Abstract
Chronic hepatitis B (CHB) patients receiving entecavir (ETV) treatment might develop low-level viremia (LLV), which is proven to be associated with worse clinical outcomes, such as risk of drug-related mutations, progression to cirrhosis, and even hepatocellular carcinoma. This real-world prospective study evaluated the efficacy and safety of switching from ETV to tenofovir alafenamide fumarate (TAF) in CHB patients with LLV. From August 2020 to August 2023, 351 ETV-experienced CHB patients with LLV were enrolled from eight hospitals. Patients either continued ETV or switched to TAF. The primary efficacy endpoint was the complete virological response (CVR) at week 48; the safety endpoint was the first occurrence of any clinical adverse event during the treatment; and the renal safety and change in blood lipids were also assessed. Inverse probability treatment weighting (IPTW) generated 350.9 cases in the ETV group and 351.4 cases in the TAF group. After the 48-week treatment, the CVR and ALT normalization rates in the TAF group were 75.3% and 67.8%, which were significantly higher than 11.4% and 17.1% in the ETV group (P < 0.001). The two strategies showed comparable impact on renal function and lipid profiles, regarding low-density lipoprotein (LDL) cholesterol and the total cholesterol to high-density lipoprotein (TC/HDL) ratio. Therefore, for ETV-treated patients with LLV, switching to TAF is superior compared with continuing ETV treatment in terms of virological and biochemical response, with non-inferior renal safety and lipid profiles.CLINICAL TRIALSThis study is registered with the Chinese Clinial Trial Registry as ChiCTR2400089257.
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Affiliation(s)
- Meng-Wen He
- Peking University 302 Clinical Medical School, Beijing, China
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Li Cui
- Department of Emergency, 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 Zhao
- Department of Interventional Radiology, the Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Wen-Zhao Luo
- Department of Hepatobiliary & Gastrointestinal Diseases, Henan Province Hospital of Traditional Chinese Medicine, Zhengzhou, Henan, China
| | - Yun-Fei Jia
- Department of Hepatobiliary & Gastrointestinal Diseases, Henan Province Hospital of Traditional Chinese Medicine, Zhengzhou, Henan, China
| | - Jie Zhou
- Department of Infectious Diseases, Xinjiang Uygur Autonomous Region Infectious Disease Hospital, Xinjiang, China
| | - Qing-Juan He
- Department II of Gastroenterology, The Eighth People’s Hospital of Qingdao, Qingdao, China
| | - Ying Dai
- Department of Gastroenterology, Qiqihar Seventh Hospital, Qiqihar, China
| | - Wei-Hua Zhang
- The Second ward, Qian 'an Infectious Disease Hospital, Tangshan, China
| | - Zhao-Xia Yu
- Liver Oncology Department, The Sixth People’s Hospital of Qingdao, Qingdao, China
| | | | - Chang Guo
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Yi-Ming Fu
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Wu-Cai Yang
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Xu-Yang Li
- Peking University 302 Clinical Medical School, Beijing, China
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Yi-Fan Guo
- Peking University 302 Clinical Medical School, Beijing, China
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Chun-Yan Wang
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Jian-Jun Wang
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Ping Li
- Integrated TCM & Western Medicine Department, Tianjin Second People’s Hospital, Tianjin, China
| | - Bing Qiao
- Liver Oncology Department, The Sixth People’s Hospital of Qingdao, Qingdao, China
| | - Dong Ji
- Peking University 302 Clinical Medical School, Beijing, China
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Beijing, China
- Chinese PLA Medical School, Beijing, Beijing, China
| | - Zhong-Bin Li
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Beijing, China
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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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Chu X, Wu Q, Kong L, Peng Q, Shen J. Multiomics Analysis Identifies Prognostic Signatures for Sepsis-Associated Hepatocellular Carcinoma in Emergency Medicine. Emerg Med Int 2024; 2024:1999820. [PMID: 39421149 PMCID: PMC11486536 DOI: 10.1155/2024/1999820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 08/06/2024] [Accepted: 08/30/2024] [Indexed: 10/19/2024] Open
Abstract
Objectives Sepsis, caused by the body's response to infection, poses a life-threatening condition and represents a significant global health challenge. Characterized by dysregulated immune response to infection, sepsis may lead to organ dysfunction and failure, ultimately resulting in high mortality rates. The liver plays a crucial role in sepsis, yet the role of differentially expressed genes in septic patients remains unclear in hepatocellular carcinoma (HCC). In this study, we aim to investigate the significance of differentially expressed genes related to sepsis in the occurrence and prognosis of tumors in HCC. Methods We conducted analyses by obtaining gene transcriptome data and clinical data of HCC cases from The Cancer Genome Atlas (TCGA). Furthermore, we obtained transcriptomic sequencing results of septic patients from the Gene Expression Omnibus (GEO) database, identified intersecting differentially expressed genes between the two, and performed survival analysis on the samples using LASSO and Cox regression analysis. Combining analyses of tumor mutation burden (TMB) and immune function, we further elucidated the mechanisms of sepsis-related genes in the prognosis and treatment of HCC. Results We established a prognostic model consisting of four sepsis-related genes: KRT20, PAEP, CCR3, and ANLN. Both the training and validation sets showed excellent outcomes in the prognosis of tumor patients, with significantly longer survival times observed in the low-risk group based on this model compared to the high-risk group. Furthermore, analyses, such as differential analysis of tumor mutation burden, immune function analysis, GO/KEGG pathway enrichment analysis, and drug sensitivity analysis, also demonstrated the potential mechanisms of action of sepsis-related genes. Conclusions Models constructed based on sepsis-related genes have shown excellent predictive ability in prognosis and differential analysis of drug sensitivity among tumor patients. These predictive models can enhance patient prognosis and inform the creation of early treatment protocols for sepsis, consequently aiding in the prevention of sepsis-induced HCC development through the modulation of the overall immune status. This may play a crucial role in patient management and immunotherapy, providing valuable reference for subsequent research.
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Affiliation(s)
- Xin Chu
- Department of Emergency, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, China
| | - Qi Wu
- Department of Emergency, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, China
| | - Linglin Kong
- Department of Infectious Disease, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, China
| | - Qiang Peng
- Department of Emergency, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, China
| | - Junhua Shen
- Department of Emergency, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, China
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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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Chen J, Feng T, Xu Q, Yu X, Han Y, Yu D, Gong Q, Xue Y, Zhang X. Risk predictive model for the development of hepatocellular carcinoma before initiating long-term antiviral therapy in patients with chronic hepatitis B virus infection. J Med Virol 2024; 96:e29884. [PMID: 39206860 DOI: 10.1002/jmv.29884] [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: 05/07/2024] [Revised: 07/28/2024] [Accepted: 08/14/2024] [Indexed: 09/04/2024]
Abstract
It is generally acknowledged that antiviral therapy can reduce the incidence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), there remains a subset of patients with chronic HBV infection who develop HCC despite receiving antiviral treatment. This study aimed to develop a model capable of predicting the long-term occurrence of HCC in patients with chronic HBV infection before initiating antiviral therapy. A total of 1450 patients with chronic HBV infection, who received initial antiviral therapy between April 2006 and March 2023 and completed long-term follow-ups, were nonselectively enrolled in this study. Least absolute shrinkage and selection operator (LASSO) and Cox regression analysis was used to construct the model. The results were validated in an external cohort (n = 210) and compared with existing models. The median follow-up time for all patients was 60 months, with a maximum follow-up time of 144 months, during which, 32 cases of HCC occurred. The nomogram model for predicting HCC based on GGT, AFP, cirrhosis, gender, age, and hepatitis B e antibody (TARGET-HCC) was constructed, demonstrating a good predictive performance. In the derivation cohort, the C-index was 0.906 (95% CI = 0.869-0.944), and in the validation cohort, it was 0.780 (95% CI = 0.673-0.886). Compared with existing models, TARGET-HCC showed promising predictive performance. Additionally, the time-dependent feature importance curve indicated that gender consistently remained the most stable predictor for HCC throughout the initial decade of antiviral therapy. This simple predictive model based on noninvasive clinical features can assist clinicians in identifying high-risk patients with chronic HBV infection for HCC before the initiation of antiviral therapy.
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Affiliation(s)
- Junjie Chen
- Department of Infectious Diseases, Research Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Tienan Feng
- Clinical Research Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qi Xu
- Department of Infectious Diseases, Research Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaoqi Yu
- Department of Infectious Diseases, Research Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yue Han
- Department of Infectious Diseases, Research Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Demin Yu
- Department of Infectious Diseases, Research Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qiming Gong
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuan Xue
- Institute of Hepatology, The Third People's Hospital of Changzhou, Changzhou, Jiangsu, China
- Department of Liver Diseases, The Third People's Hospital of Changzhou, Changzhou, Jiangsu, China
| | - Xinxin Zhang
- Department of Infectious Diseases, Research Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Clinical Research Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Zhang Y, Wan G, Li H, Gao L, Liu N, Gao P, Liu Y, Gao X, Duan X. A prediction nomogram for hepatitis B virus-associated hepatocellular carcinoma. Scand J Gastroenterol 2024; 59:70-77. [PMID: 37647217 DOI: 10.1080/00365521.2023.2252546] [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: 03/22/2023] [Revised: 08/16/2023] [Accepted: 08/23/2023] [Indexed: 09/01/2023]
Abstract
BACKGROUND The present study aimed to develop and validate a new nomogram for predicting the incidence of hepatocellular carcinoma (HCC) among chronic hepatitis B (CHB) patients receiving antiviral therapy from real-world data. METHODS The nomogram was established based on a real-world retrospective study of 764 patients with HBV from October 2008 to July 2020. A predictive model for the incidence of HCC was developed by multivariable Cox regression, and a nomogram was constructed. The predictive accuracy and discriminative ability of the nomogram were assessed by the concordance index (C-index), calibration curves, and decision curve analysis (DCA). Risk group stratification was performed to assess the predictive capacity of the nomogram. The nomogram was compared to three current commonly used predictive models. RESULTS A total of 764 patients with HBV were recruited for this study. Age, family history of HCC, alcohol consumption, and Aspartate aminotransferase-to-Platelet Ratio Index (APRI) were all independent risk predictors of HCC in CHB patients. The constructed nomogram had good discrimination with a C-index of 0.811. The calibration curve and DCA also proved the reliability and accuracy of the nomogram. Three risk groups (low, moderate, and high) with significantly different prognoses were identified (p < 0.001). The model's performance was significantly better than that of other risk models. CONCLUSIONS The nomogram was superior in predicting HCC risk among CHB patients who received antiviral treatment. The model can be utilized in clinical practice to aid decision-making on the strategy of long-term HCC surveillance, especially for moderate- and high-risk patients.
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Affiliation(s)
- Yijin Zhang
- Department of General Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Gang Wan
- Department of Medical Record, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Hongjie Li
- Department of General Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Lili Gao
- Department of General Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Nan Liu
- Department of General Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ping Gao
- Department of General Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yaping Liu
- Department of General Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xuesong Gao
- Department of General Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xuefei Duan
- Department of General Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
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Hao X, Fan R, Zeng HM, Hou JL. Hepatocellular Carcinoma Risk Scores from Modeling to Real Clinical Practice in Areas Highly Endemic for Hepatitis B Infection. J Clin Transl Hepatol 2023; 11:1508-1519. [PMID: 38161501 PMCID: PMC10752803 DOI: 10.14218/jcth.2023.00087] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 05/04/2023] [Accepted: 06/02/2023] [Indexed: 01/03/2024] Open
Abstract
Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers and represents a global health challenge. Liver cancer ranks third in cancer-related mortality with 830,000 deaths and sixth in incidence with 906,000 new cases annually worldwide. HCC most commonly occurs in patients with underlying liver disease, especially chronic hepatitis B virus (HBV) infection in highly endemic areas. Predicting HCC risk based on scoring models for patients with chronic liver disease is a simple, effective strategy for identifying and stratifying patients to improve the early diagnosis rate and prognosis of HCC. We examined 23 HCC risk scores published worldwide in CHB patients with (n=10) or without (n=13) antiviral treatment. We also described the characteristics of the risk score's predictive performance and application status. In the future, higher predictive accuracy could be achieved by combining novel technologies and machine learning algorithms to develop and update HCC risk score models and integrated early warning and diagnosis systems for HCC in hospitals and communities.
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Affiliation(s)
- Xin Hao
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Guangdong Provincial Institute of Liver Diseases, Guangzhou, Guangdong, China
| | - Rong Fan
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Guangdong Provincial Institute of Liver Diseases, Guangzhou, Guangdong, China
| | - Hong-Mei Zeng
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jin-Lin Hou
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Guangdong Provincial Institute of Liver Diseases, Guangzhou, Guangdong, 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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Lee YT, Fujiwara N, Yang JD, Hoshida Y. Risk stratification and early detection biomarkers for precision HCC screening. Hepatology 2023; 78:319-362. [PMID: 36082510 PMCID: PMC9995677 DOI: 10.1002/hep.32779] [Citation(s) in RCA: 60] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 08/25/2022] [Accepted: 08/28/2022] [Indexed: 12/08/2022]
Abstract
Hepatocellular carcinoma (HCC) mortality remains high primarily due to late diagnosis as a consequence of failed early detection. Professional societies recommend semi-annual HCC screening in at-risk patients with chronic liver disease to increase the likelihood of curative treatment receipt and improve survival. However, recent dynamic shift of HCC etiologies from viral to metabolic liver diseases has significantly increased the potential target population for the screening, whereas annual incidence rate has become substantially lower. Thus, with the contemporary HCC etiologies, the traditional screening approach might not be practical and cost-effective. HCC screening consists of (i) definition of rational at-risk population, and subsequent (ii) repeated application of early detection tests to the population at regular intervals. The suboptimal performance of the currently available HCC screening tests highlights an urgent need for new modalities and strategies to improve early HCC detection. In this review, we overview recent developments of clinical, molecular, and imaging-based tools to address the current challenge, and discuss conceptual framework and approaches of their clinical translation and implementation. These encouraging progresses are expected to transform the current "one-size-fits-all" HCC screening into individualized precision approaches to early HCC detection and ultimately improve the poor HCC prognosis in the foreseeable future.
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Affiliation(s)
- Yi-Te Lee
- California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, California
| | - Naoto Fujiwara
- Liver Tumor Translational Research Program, Simmons Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Ju Dong Yang
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California; Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, Los Angeles, California; Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Yujin Hoshida
- Liver Tumor Translational Research Program, Simmons Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
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11
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Li J, Dong XQ, Cao LH, Zhang ZQ, Zhao WF, Shang QH, Zhang DZ, Ma AL, Xie Q, Gui HL, Zhang G, Liu YX, Shang J, Xie SB, Liu YQ, Zhang C, Wang GQ, Zhao H. Factors associated with persistent positive in HBV DNA level in patients with chronic Hepatitis B receiving entecavir treatment. Front Cell Infect Microbiol 2023; 13:1151899. [PMID: 37396307 PMCID: PMC10311917 DOI: 10.3389/fcimb.2023.1151899] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Accepted: 05/12/2023] [Indexed: 07/04/2023] Open
Abstract
Introduction The clinical significance of persistent positive in Hepatitis B Virus (HBV) DNA level in patients receiving antiviral therapy is not well known. We investigated factors associated with persistent viremia (PV) in patients with chronic hepatitis B (CHB) given 78-week entecavir. Methods A total of 394 treatment-naïve CHB patients who had undergone liver biopsy at baseline and week 78 of treatment were analyzed in this prospective multicentre study. We identified patients with PV (above the lower limit of quantification, 20 IU/ml) after 78 weeks of entecavir therapy. Stepwise, forward, multivariate regression analyses of specified baseline parameters were apllied to identify factors associated with PV. Futhermore, we assessed the incidence of hepatocellular carcinoma (HCC) in all patients using models of the risk of HCC development. Results Of the 394 patients, 90 (22.8%) still with PV after 78-week antiviral treatment. Factors associated significantly with PV (vs complete virological response, CVR) were HBV DNA level ≥8 log10 IU/mL (OR, 3.727; 95% CI, 1.851-7.505; P < 0.001), Anti-HBc level < 3 log10 IU/mL (OR, 2.384; 95% CI, 1.223-4.645; P=0.011), and HBeAg seropositivity (OR, 2.871; 95% CI, 1.563-5.272; P < 0.001). Patients with PV were less likely to have fibrosis progression and HCC development than those with the CVR. Of the 11 HBeAg-positive patients with HBV DNA level ≥8 log10 IU/mL and Anti-HBc level < 3 log10 IU/mL at baseline, 9 (81.8%) had persistent positivity in HBV DNA level and 0 had fibrosis progression at week 78 of treatment. Discussion In conclusion, HBV DNA level ≥8 log10 IU/mL, Anti-HBc level < 3 log10 IU/mL and HBeAg seropositivity at baseline contribute to PV in patients with CHB receiving 78-week antiviral treatment. In addition, the rate of fibrosis progression and the risk of HCC development in patients with PV were kept low. The complete protocol for the clinical trial has been registered at clinicaltrials.gov (NCT01962155 and NCT03568578).
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Affiliation(s)
- Jun Li
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, China
| | - Xiao-Qin Dong
- Department and Institute of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Li-Hua Cao
- Department of Hepatology, The Third Hospital of Qinhuangdao, Qinhuangdao, China
| | - Zhan-Qing Zhang
- Department of Infectious Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Wei-Feng Zhao
- Department of Infectious Disease, Xinxiang Medical University Affiliated Third Hospital, Xinxiang, China
| | - Qing-Hua Shang
- Department of Hepatology, No.88 Hospital of Chinese People’s Liberation Army (PLA), Jinan, China
| | - Da-Zhi Zhang
- Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - An-Lin Ma
- Department of Infectious Disease, China-Japan Friendship Hospital, Beijing, China
| | - Qing Xie
- Department of Infectious Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Hong-Lian Gui
- Department of Infectious Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Guo Zhang
- Department of Gastroenterology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | - Ying-Xia Liu
- Department of Infectious Diseases, The Third People’s Hospital of Shenzhen, Shenzhen, China
| | - Jia Shang
- Department of Infectious Diseases, The People’s Hospital of Henan, Zhengzhou, China
| | - Shi-Bin Xie
- Department of Infectious Disease, The Third Affiliated Hospital of Sun-Yat Sen University, Guangzhou, China
| | - Yi-Qi Liu
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, China
| | - Chi Zhang
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, China
| | - Gui-Qiang Wang
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, China
- The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, Zhejiang, China
- Department of Hepatology, Peking University International Hospital, Beijing, China
| | - Hong Zhao
- Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, China
- Department of Hepatology, Peking University International Hospital, Beijing, China
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Lee JH, Shin SK, Kang SH, Kim TH, Yim HJ, Yim SY, Lee YS, Jung YK, Kim JH, Seo YS, Yeon JE, Kwon OS, Um SH, Byun KS. Long-Term Prediction Model for Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Receiving Antiviral Therapy: Based on Data from Korean Patients. J Clin Med 2022; 11:jcm11226613. [PMID: 36431090 PMCID: PMC9697157 DOI: 10.3390/jcm11226613] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 10/31/2022] [Accepted: 11/02/2022] [Indexed: 11/09/2022] Open
Abstract
Predicting the development of hepatocellular carcinoma (HCC) is a key clinical issue in patients with chronic hepatitis B (CHB). The aim of this study was to develop a precise and simple HCC risk score for up to 10 years. A total of 1895 CHB patients treated with entecavir or tenofovir disoproxil fumarate were retrospectively recruited and randomized into derivation (n = 1239) and validation cohorts (n = 656). Variables proven to be independent risk factors for HCC in the derivation cohort were used to develop the prediction model. The ACCESS-HCC model included five variables (age, cirrhosis, consumption of ethanol, liver stiffness, and serum alanine aminotransferase). Areas under curves were 0.798, 0.762, and 0.883 for HCC risk at 3, 5, and 10 years, respectively, which were higher than those of other prediction models. The scores were categorized according to significantly different HCC incidences: 0-4, low; 5-8, intermediate; and 9-14, high-risk. The annual incidence rates were 0.5%, 3.2%, and 11.3%, respectively. The performance of this model was validated in an independent cohort. The ACCESS-HCC model shows improved long-term prediction and provides three distinct risk categories for HCC in CHB patients receiving antiviral therapy. Further research is needed for external validation using larger cohorts.
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Affiliation(s)
- Ji Hun Lee
- Department of Medicine, Korea University College of Medicine, Seoul 02841, Korea
| | - Seung Kak Shin
- Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon 21565, Korea
| | - Seong Hee Kang
- Department of Internal Medicine, Inje University College of Medicine, Seoul 01757, Korea
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju 26426, Korea
| | - Tae Hyung Kim
- Department of Medicine, Korea University College of Medicine, Seoul 02841, Korea
- Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, Korea
- Correspondence: (H.J.Y.); (T.H.K.)
| | - Hyung Joon Yim
- Department of Medicine, Korea University College of Medicine, Seoul 02841, Korea
- Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, Korea
- Correspondence: (H.J.Y.); (T.H.K.)
| | - Sun Young Yim
- Department of Medicine, Korea University College of Medicine, Seoul 02841, Korea
- Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, Korea
| | - Young-Sun Lee
- Department of Medicine, Korea University College of Medicine, Seoul 02841, Korea
- Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, Korea
| | - Young Kul Jung
- Department of Medicine, Korea University College of Medicine, Seoul 02841, Korea
- Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, Korea
| | - Ji Hoon Kim
- Department of Medicine, Korea University College of Medicine, Seoul 02841, Korea
- Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, Korea
| | - Yeon Seok Seo
- Department of Medicine, Korea University College of Medicine, Seoul 02841, Korea
- Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, Korea
| | - Jong Eun Yeon
- Department of Medicine, Korea University College of Medicine, Seoul 02841, Korea
- Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, Korea
| | - Oh Sang Kwon
- Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon 21565, Korea
| | - Soon Ho Um
- Department of Medicine, Korea University College of Medicine, Seoul 02841, Korea
- Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, Korea
| | - Kwan Soo Byun
- Department of Medicine, Korea University College of Medicine, Seoul 02841, Korea
- Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, Korea
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Fraquelli M, Nadarevic T, Colli A, Manzotti C, Giljaca V, Miletic D, Štimac D, Casazza G. Contrast-enhanced ultrasound for the diagnosis of hepatocellular carcinoma in adults with chronic liver disease. Cochrane Database Syst Rev 2022; 9:CD013483. [PMID: 36053210 PMCID: PMC9438628 DOI: 10.1002/14651858.cd013483.pub2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Hepatocellular carcinoma occurs mostly in people with chronic liver disease. Worldwide, it ranks sixth in terms of incidence of cancer, and fourth in terms of cancer-related deaths. Contrast-enhanced ultrasound (CEUS) is used as an add-on test to confirm the presence of focal liver lesions suspected as hepatocellular carcinoma after prior diagnostic tests such as abdominal ultrasound or measurement of alpha-foetoprotein, or both. According to guidelines, a single contrast-enhanced imaging investigation, with either computed tomography (CT) or magnetic resonance imaging (MRI), may show the typical hepatocellular carcinoma hallmarks in people with cirrhosis, which will be sufficient to diagnose hepatocellular carcinoma. However, a significant number of hepatocellular carcinomas show atypical imaging features, and therefore, are missed at imaging. Dynamic CEUS images are obtained similarly to CT and MRI images. CEUS differentiates between arterial and portal venous phases, in which sonographic hepatocellular carcinoma hallmarks, such as arterial hyperenhancement and subsequent washout appearance, are investigated. The advantages of CEUS over CT and MRI include real-time imaging, use of contrast agents that do not contain iodine and are not nephrotoxic, and quick image acquisition. Despite the advantages, the use of CEUS in the diagnostic algorithm for HCC remains controversial, with disagreement on relevant guidelines. There is no clear evidence of the benefit of surveillance programmes in terms of overall survival as the conflicting results can be a consequence of an inaccurate detection, ineffective treatment, or both. Therefore, assessing the diagnostic accuracy of CEUS may clarify whether the absence of benefit could be related to underdiagnosis. Furthermore, an assessment of the accuracy of CEUS for the diagnosis of hepatocellular carcinoma is needed for either diagnosing hepatocellular carcinoma or ruling it out in people with chronic liver disease who are not included in surveillance programmes. OBJECTIVES 1. To assess the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) for the diagnosis of hepatocellular carcinoma of any size and at any stage in adults with chronic liver disease, in a surveillance programme or in a clinical setting. 2. To assess the diagnostic accuracy of CEUS for the diagnosis of resectable hepatocellular carcinoma in people with chronic liver disease and identify potential sources of heterogeneity in the results. SEARCH METHODS We used standard, extensive Cochrane search methods. The last date of search was 5 November 2021. SELECTION CRITERIA We included studies assessing the diagnostic accuracy of CEUS for the diagnosis of hepatocellular carcinoma in adults with chronic liver disease, with cross-sectional designs, using one of the acceptable reference standards, such as pathology of the explanted liver, and histology of resected or biopsied focal liver lesion with at least a six-month follow-up. DATA COLLECTION AND ANALYSIS We used standard Cochrane methods to screen studies, extract data, and assess the risk of bias and applicability concerns, using the QUADAS-2 checklist. We used the bivariate model and provided estimates of summary sensitivity and specificity. We assessed the certainty of the evidence using GRADE. We presented uncertainty-of-the-accuracy estimates using 95% confidence intervals (CIs). MAIN RESULTS We included 23 studies with 6546 participants. Studies were published between 2001 and 2021. We judged all 23 studies at high-risk of bias in at least one domain, and 13/23 studies at high concern for applicability. Most studies used different reference standards to exclude the presence of the target condition. The time interval between the index test and the reference standard was rarely defined. We also had major concerns on their applicability due to the characteristics of the participants. - CEUS for hepatocellular carcinoma of any size and stage: sensitivity 77.8% (95% CI 69.4% to 84.4%) and specificity 93.8% (95% CI 89.1% to 96.6%) (23 studies, 6546 participants; very low-certainty evidence). - CEUS for resectable hepatocellular carcinoma: sensitivity 77.5% (95% CI 62.9% to 87.6%) and specificity 92.7% (95% CI 86.8% to 96.1%) (13 studies, 1257 participants; low-certainty evidence). The observed heterogeneity in the results remains unexplained. The sensitivity analyses, including only studies with clearly prespecified positivity criteria and only studies in which the reference standard results were interpreted with no knowledge of the results about the index test, showed no differences in the results. AUTHORS' CONCLUSIONS We found that by using CEUS, as an add-on test following abdominal ultrasound, to diagnose hepatocellular carcinoma of any size and stage, 22% of people with hepatocellular carcinoma would be missed, and 6% of people without hepatocellular carcinoma would unnecessarily undergo further testing or inappropriate treatment. As to resectable hepatocellular carcinoma, we found that 23% of people with resectable hepatocellular carcinoma would incorrectly be unresected, while 8% of people without hepatocellular carcinoma would undergo further inappropriate testing or treatment. The uncertainty resulting from the high risk of bias of the included studies, heterogeneity, and imprecision of the results and concerns on their applicability limit our ability to draw confident conclusions.
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Affiliation(s)
- Mirella Fraquelli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca´ Granda - Ospedale Maggiore Policlinico, Milan, Italy
| | - Tin Nadarevic
- Department of Radiology, Clinical Hospital Centre Rijeka, Rijeka, Croatia
| | - Agostino Colli
- Department of Transfusion Medicine and Haematology, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milano, Italy
| | - Cristina Manzotti
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca´ Granda - Ospedale Maggiore Policlinico, Milan, Italy
| | - Vanja Giljaca
- Department of Gastroenterology, Heart of England NHS Foundation Trust, Birmingham, UK
| | - Damir Miletic
- Department of Radiology, Clinical Hospital Centre Rijeka, Rijeka, Croatia
| | - Davor Štimac
- Department of Gastroenterology, Clinical Hospital Centre Rijeka, Rijeka, Croatia
| | - Giovanni Casazza
- Department of Clinical Sciences and Community Health - Laboratory of Medical Statistics, Biometry and Epidemiology "G.A. Maccacaro", Università degli Studi di Milano, Milan, Italy
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Risk prediction models for hepatocellular carcinoma in chronic hepatitis B patients on antiviral therapy: A meta-analysis. Clin Res Hepatol Gastroenterol 2022; 46:101930. [PMID: 35460902 DOI: 10.1016/j.clinre.2022.101930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 04/11/2022] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS The risk prediction of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) is a challenge especially in the era of antiviral therapy. The aim of this meta-analysis was to comprehensively evaluate the performance of existing HCC prediction scores in HCC prediction on antivirals. METHODS We searched PubMed, Web of Science and Cochrane Library for relevant prospective studies from the inception to August 24, 2021. The areas under the receiver operating characteristics (AUROCs) and their relevant 95% confidence intervals (CIs) of the risk prediction models were calculated. RESULTS Nine eligible articles with 21561 patients (HCC developed in 947patients, 4.39%; mean follow-up duration: 5 years) and 14 predictive risk scores were included. The pooled AUROC of all included scores for 3-year and 5-year prediction of HCC was 0.72 (95%CI 0.68-0.76) and 0.80 (95%CI 0.76-0.83), with the corresponding sensitivity of 0.84 (95% CI 0.71-0.92) and 0.91(95% CI 0.86-0.95) and specificity of 0.46 (95% CI 0.30-0.63) and 0.48 (95% CI 0.37-0.59), respectively. All the 14 prediction models, as a whole, performed well in different populations, whether they include factor cirrhotic status or not; while those integrated viral load were less accurate (sensitivity 0.78, specificity of 0.57). CONCLUSIONS In patients with CHB on antivirals, the scores included in our meta-analysis have been proven to be useful for mid-long term HCC prediction. Viral load seems not useful, whereas cirrhosis and its objective surrogates remain the predominant components. These models are expected to translate clinical benefits if used in complementarity with regular HCC surveillance.
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Hepatitis B Virus-Associated Hepatocellular Carcinoma. Viruses 2022; 14:v14050986. [PMID: 35632728 PMCID: PMC9146458 DOI: 10.3390/v14050986] [Citation(s) in RCA: 89] [Impact Index Per Article: 29.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 05/02/2022] [Accepted: 05/03/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) is DNA-based virus, member of the Hepadnaviridae family, which can cause liver disease and increased risk of hepatocellular carcinoma (HCC) in infected individuals, replicating within the hepatocytes and interacting with several cellular proteins. Chronic hepatitis B can progressively lead to liver cirrhosis, which is an independent risk factor for HCC. Complications as liver decompensation or HCC impact the survival of HBV patients and concurrent HDV infection worsens the disease. The available data provide evidence that HBV infection is associated with the risk of developing HCC with or without an underlying liver cirrhosis, due to various direct and indirect mechanisms promoting hepatocarcinogenesis. The molecular profile of HBV-HCC is extensively and continuously under study, and it is the result of altered molecular pathways, which modify the microenvironment and lead to DNA damage. HBV produces the protein HBx, which has a central role in the oncogenetic process. Furthermore, the molecular profile of HBV-HCC was recently discerned from that of HDV-HCC, despite the obligatory dependence of HDV on HBV. Proper management of the underlying HBV-related liver disease is fundamental, including HCC surveillance, viral suppression, and application of adequate predictive models. When HBV-HCC occurs, liver function and HCC characteristics guide the physician among treatment strategies but always considering the viral etiology in the treatment choice.
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Kubota N, Fujiwara N, Hoshida Y. Liver cancer risk-predictive molecular biomarkers specific to clinico-epidemiological contexts. Adv Cancer Res 2022; 156:1-37. [PMID: 35961696 PMCID: PMC7616039 DOI: 10.1016/bs.acr.2022.01.005] [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] [Indexed: 11/24/2022]
Abstract
Hepatocellular carcinoma (HCC) risk prediction is increasingly important because of the low annual HCC incidence in patients with the rapidly emerging non-alcoholic fatty liver disease or cured HCV infection. To date, numerous clinical HCC risk biomarkers and scores have been reported in literature. However, heterogeneity in clinico-epidemiological context, e.g., liver disease etiology, patient race/ethnicity, regional environmental exposure, and lifestyle-related factors, obscure their real clinical utility and applicability. Proper characterization of these factors will help refine HCC risk prediction according to certain clinical context/scenarios and contribute to improved early HCC detection. Molecular factors underlying the clinical heterogeneity encompass various features in host genetics, hepatic and systemic molecular dysregulations, and cross-organ interactions, which may serve as clinical-context-specific biomarkers and/or therapeutic targets. Toward the goal to enable individual-risk-based HCC screening by incorporating the HCC risk biomarkers/scores, their assessment in patient with well-defined clinical context/scenario is critical to gauge their real value and to maximize benefit of the tailored patient management for substantial improvement of the poor HCC prognosis.
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Affiliation(s)
- Naoto Kubota
- Liver Tumor Translational Research Program, Simmons Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States
| | - Naoto Fujiwara
- Liver Tumor Translational Research Program, Simmons Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States; Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yujin Hoshida
- Liver Tumor Translational Research Program, Simmons Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States.
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Yilma M, Saxena V, Mehta N. Models to Predict Development or Recurence of Hepatocellular Carcinoma (HCC) in Patients with Advanced Hepatic Fibrosis. Curr Gastroenterol Rep 2022; 24:1-9. [PMID: 35142988 PMCID: PMC8891098 DOI: 10.1007/s11894-022-00835-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
PURPOSE OF REVIEW Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death in the United States (U.S.).1 The purpose of this review is to highlight published models that predict development of HCC and estimate risk of HCC recurrence after treatments. RECENT FINDINGS There have been several models created for both de novo HCC and HCC recurrence, with the more recent models using a combination of age, sex, decompensation, and laboratory values (platelet count, albumin, bilirubin), and liver disease etiology to predict both 5 and 10-year HCC incidence. For chronic hepatitis C, sustained virologic response has been a useful component of understanding HCC risk reduction. BMI and diabetes have been utilized in non-alcoholic fatty liver disease (NAFLD) models to predict HCC risk. For HCC recurrence after treatment (for both surgical resection and liver transplant), tumor size and number, vascular invasion, alpha-fetoprotein (AFP) and neutrophil to lymphocyte ratio (NLR) are all components of HCC recurrence risk models. Although numerous HCC risk prediction models have been established over the last several years, challenges remain including how to best incorporate these models into clinical practice, improve surveillance for NAFLD-HCC development, and determine timing and duration of post-resection recurrence surveillance.
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Affiliation(s)
- Mignote Yilma
- Department of Surgery, University of California, San Francisco, CA, USA
| | - Varun Saxena
- Department of Gastroenterology and Transplant Hepatology, Kaiser Permanente South San Francisco, San Francisco, CA, USA
| | - Neil Mehta
- Division of Gastroenterology, University of California, San Francisco, CA, USA
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Tong L, Yan C, Wang M, Yang J, Wang H, Wang Y. Prognostic Value of Serum Exosomal AHCY Expression in Hepatitis B-Induced Liver Cirrhosis. Front Med (Lausanne) 2021; 8:777452. [PMID: 34820406 PMCID: PMC8606640 DOI: 10.3389/fmed.2021.777452] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Accepted: 10/11/2021] [Indexed: 12/12/2022] Open
Abstract
Objective: We aimed to investigate serum exosomal adenosylhomocysteinase (AHCY) expression in hepatitis B-induced liver cirrhosis (HBV-LC) patients and to determine the prognostic value of serum exosomal AHCY. Methods: We collected serum samples from 100 patients with chronic hepatitis B (CHB) and from 114 HBV-LC patients to test serum exosomal AHCY expression using ELISA. Results: Compared with the CHB and Grade A and B HBV-LC groups, the level of exosomal AHCY expression was significantly higher in the HBV-LC group [376.62 (291.50-448.02) vs. 248.12 (189.28-324.63), P > 0.001] and the Grade C HBV-LC group [408.70 (365.63-465.76) vs. 279.76 (215.16-336.07), P > 0.001], respectively. Serum exosomal AHCY expression and MELD score had a significant positive correlation (r = 0.844, P < 0.001). Survival curve analysis showed that patients with low exosomal AHCY expression had significantly longer survival than patients with high exosomal AHCY expression (P = 0.0038). The receiver operating characteristics (ROC) curve showed that the area under the curve (AUC) value for the mortality prediction ability of serum exosomal AHCY in HBV-LC patients was 0.921, which was higher than the values for the MELD score (AUC 0.815) and Child-Pugh classification (AUC 0.832), with a sensitivity and specificity of 93.41 and 76.00%, respectively. Conclusions: The serum exosomal AHCY level is a novel potential prognostic biomarker in HBV-LC patients, which may be great significance for the prognosis of HBV-LC patients.
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Affiliation(s)
- Ling Tong
- Department of Clinical Laboratory, The First Affiliated Hospital, College of Medicine, Zhejiang University School of Medicine, Hangzhou, China
| | - Cuilin Yan
- Department of Clinical Laboratory, The First Affiliated Hospital, College of Medicine, Zhejiang University School of Medicine, Hangzhou, China
| | - Minjie Wang
- Department of Clinical Laboratory, The First Affiliated Hospital, College of Medicine, Zhejiang University School of Medicine, Hangzhou, China
| | - Jiajia Yang
- Department of Infection Management, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China
| | - Hongmei Wang
- Department of Infection Management, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China
| | - Ying Wang
- Department of Infection Management, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China
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19
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Reporting and Performance of Hepatocellular Carcinoma Risk Prediction Models: Based on TRIPOD Statement and Meta-Analysis. Can J Gastroenterol Hepatol 2021; 2021:9996358. [PMID: 34513751 PMCID: PMC8433031 DOI: 10.1155/2021/9996358] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Revised: 07/05/2021] [Accepted: 07/23/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The performance of risk prediction models for hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) was uncertain. The aim of the study was to critically evaluate the reports of transparent and external validation performances of these prediction models based on system review and meta-analysis. METHODS A systematic search of the Web of Science and PubMed was performed for studies published until October 17, 2020. The transparent reporting of a multivariable prediction model for the individual prognosis or diagnosis (TRIPOD) tool was used to critically evaluate the quality of external validation reports for six models (CU-HCC, GAG-HCC, PAGE-B, mPAGE-B, REACH-B, and mREACH-B). The area under the receiver operator characteristic curve (AUC) values was to estimate the pooled external validating performance based on meta-analysis. Subgroup analysis and metaregression were also performed to explore heterogeneity. RESULTS Our meta-analysis included 22 studies published between 2011 and 2020. The compliance of the included studies to TRIPOD ranged from 59% to 90% (median, 74%; interquartile range (IQR), 70%, 79%). The AUC values of the six models ranged from 0.715 to 0.778. In the antiviral therapy subgroups, the AUC values of mREACH-B, GAG-HCC, and mPAGE-B were 0.785, 0.760, and 0.778, respectively. In the cirrhosis subgroup, all models had poor discrimination performance (AUC < 0.7). CONCLUSIONS A full report of calibration and handling of missing values would contribute to a greater improvement in the quality of external validation reports for CHB-related HCC risk prediction. It was necessary to develop a specific HCC risk prediction model for patients with cirrhosis.
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20
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Hsu YC, Tseng CH, Huang YT, Yang HI. Application of Risk Scores for Hepatocellular Carcinoma in Patients with Chronic Hepatitis B: Current Status and Future Perspective. Semin Liver Dis 2021; 41:285-297. [PMID: 34161993 DOI: 10.1055/s-0041-1730924] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Accurate risk prediction for hepatocellular carcinoma (HCC) among patients with chronic hepatitis B (CHB) may guide treatment strategies including initiation of antiviral therapy and also inform implementation of HCC surveillance. There have been 26 risk scores developed to predict HCC in CHB patients with (n = 14) or without (n = 12) receiving antiviral treatment; all of them invariably include age in the scoring formula. Virological biomarkers of replicative activities (i.e., hepatitis B virus DNA level or hepatitis B envelope antigen status) are frequently included in the scores derived from patients with untreated CHB, whereas measurements that gauge severity of liver fibrosis and/or reserve of hepatic function (i.e., cirrhosis diagnosis, liver stiffness measurement, platelet count, or albumin) are essential components in the scores developed from treated patients. External validation is a prerequisite for clinical application but not yet performed for all scores. For the future, higher predictive accuracy may be achieved with machine learning based on more comprehensive data.
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Affiliation(s)
- Yao-Chun Hsu
- Center for Liver Diseases, E-Da Hospital, Kaohsiung, Taiwan.,School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan.,Department of Medicine, Fu-Jen Catholic University Hospital, New Taipei, Taiwan.,Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan
| | - Cheng-Hao Tseng
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan.,Division of Gastroenterology and Hepatology, E-Da Cancer Hospital, Kaohsiung, Taiwan
| | - Yen-Tsung Huang
- Institute of Statistical Science, Academia Sinica, Taipei, Taiwan
| | - Hwai-I Yang
- Genomics Research Center, Academia Sinica, Taipei, Taiwan.,Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.,Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Biomedical Translation Research Center, Academia Sinica, Taipei, Taiwan
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21
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Lu H, Yi W, Sun F, Zeng Z, Zhang L, Li M, Xie Y. Comprehensive investigation of HBV-related hepatocellular carcinoma and choice of anti-HBV therapy. BIOSAFETY AND HEALTH 2021. [DOI: 10.1016/j.bsheal.2021.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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22
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Florea M, Serban T, Tirpe GR, Tirpe A, Lupsor-Platon M. Noninvasive Assessment of Hepatitis C Virus Infected Patients Using Vibration-Controlled Transient Elastography. J Clin Med 2021; 10:jcm10122575. [PMID: 34200885 PMCID: PMC8230562 DOI: 10.3390/jcm10122575] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 06/06/2021] [Accepted: 06/08/2021] [Indexed: 02/08/2023] Open
Abstract
Chronic infection with hepatitis C virus (HCV) is one of the leading causes of cirrhosis and hepatocellular carcinoma (HCC). Surveillance of these patients is an essential strategy in the prevention chain, including in the pre/post-antiviral treatment states. Ultrasound elastography techniques are emerging as key methods in the assessment of liver diseases, with a number of advantages such as their rapid, noninvasive, and cost-effective characters. The present paper critically reviews the performance of vibration-controlled transient elastography (VCTE) in the assessment of HCV patients. VCTE measures liver stiffness (LS) and the ultrasonic attenuation through the embedded controlled attenuation parameter (CAP), providing the clinician with a tool for assessing fibrosis, cirrhosis, and steatosis in a noninvasive manner. Moreover, standardized LS values enable proper staging of the underlying fibrosis, leading to an accurate identification of a subset of HCV patients that present a high risk for complications. In addition, VCTE is a valuable technique in evaluating liver fibrosis prior to HCV therapy. However, its applicability in monitoring fibrosis regression after HCV eradication is currently limited and further studies should focus on extending the boundaries of VCTE in this context. From a different perspective, VCTE may be effective in identifying clinically significant portal hypertension (CSPH). An emerging prospect of clinical significance that warrants further study is the identification of esophageal varices. Our opinion is that the advantages of VCTE currently outweigh those of other surveillance methods.
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Affiliation(s)
- Mira Florea
- Community Medicine Department, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
| | - Teodora Serban
- Medical Imaging Department, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
| | - George Razvan Tirpe
- Department of Radiology and Medical Imaging, County Emergency Hospital Cluj-Napoca, 3-5 Clinicilor Street, 400000 Cluj-Napoca, Romania;
| | - Alexandru Tirpe
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 23 Marinescu Street, 400337 Cluj-Napoca, Romania;
| | - Monica Lupsor-Platon
- Medical Imaging Department, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
- Medical Imaging Department, Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
- Correspondence:
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23
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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] [MESH Headings] [Grants] [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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24
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Guo J, Gao XS. Prediction models for development of hepatocellular carcinoma in chronic hepatitis B patients. World J Clin Cases 2021; 9:3238-3251. [PMID: 34002133 PMCID: PMC8107908 DOI: 10.12998/wjcc.v9.i14.3238] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 02/11/2021] [Accepted: 03/17/2021] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC) is a major health problem in Asian-Pacific regions. Antiviral therapy reduces, but does not completely prevent, HCC development. Thus, there is a need for accurate risk prediction to assist prognostication and decisions on the need for antiviral therapy and HCC surveillance. A few risk scores have been developed to predict the occurrence of HCC in CHB patients. Initially, the scores were derived from untreated CHB patients. With the development and extensive clinical application of nucleos(t)ide analog(s) (NA), the number of risk scores based on treated CHB patients has increased gradually. The components included in risk scores may be categorized into host factors and hepatitis B virus factors. Hepatitis activities, hepatitis B virus factors, and even liver fibrosis or cirrhosis are relatively controlled by antiviral therapy. Therefore, variables that are more dynamic during antiviral therapy have since been included in risk scores. However, host factors are more difficult to modify. Most existing scores derived from Asian populations have been confirmed to be accurate in predicting HCC development in CHB patients from Asia, while these scores have not offered excellent predictability in Caucasian patients. These findings support that more relevant variables should be considered to provide individualized predictions that are easily applied to CHB patients of different ethnicities. CHB patients should receive different intensities of HCC surveillance according to their risk category.
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Affiliation(s)
- Jiang Guo
- Department of Interventional Oncology, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Xue-Song Gao
- Department of General Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
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25
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Güzelbulut F, Gökçen P, Can G, Adalı G, Değirmenci Saltürk AG, Bahadır Ö, Özdil K, Doğanay HL. Validation of the HCC-RESCUE score to predict hepatocellular carcinoma risk in Caucasian chronic hepatitis B patients under entecavir or tenofovir therapy. J Viral Hepat 2021; 28:826-836. [PMID: 33586270 DOI: 10.1111/jvh.13485] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Revised: 01/12/2021] [Accepted: 01/29/2021] [Indexed: 02/06/2023]
Abstract
The HCC-RESCUE score was developed to predict hepatocellular carcinoma (HCC) risk in Korean chronic hepatitis B (CHB) patients under entecavir therapy. We aimed to validate the HCC-RESCUE score to predict HCC risk in Caucasian CHB patients under entecavir or tenofovir therapy and to compare the predictive performance of the HCC-RESCUE score with those of the CAMD, PAGE-B and modified PAGE-B (mPAGE-B) scores. The study included 647 nucleos(t)ide analogue-naive noncirrhotic and compensated/decompensated cirrhotic patients who had received entecavir or tenofovir for ≥6 months and did not develop HCC during the first 6 months of therapy. Patients with HCC-RESCUE scores ≤64, 65-84 and ≥85 points were classified into low-, intermediate- and high-risk groups, respectively. The AUROCs of the HCC-RESCUE, CAMD, PAGE-B and mPAGE-B scores to predict HCC risk at 5 years were 0.875, 0.870, 0.866 and 0.880, and those at 10 years were 0.862, 0.845, 0.841 and 0.862, respectively (both p > .05). Cumulative HCC incidences at 5 years were 0.0%, 10.5% and 15.8%, and those at 10 years were 1.4%, 15.5% and 24.9%, respectively, in the low-, intermediate- and high-risk groups based on the HCC-RESCUE score (both log rank p < .001). In the entecavir versus tenofovir cohorts, the AUROCs of the HCC-RESCUE score to predict HCC risk at 5 and 10 years were 0.831 versus 0.898 and 0.803 versus 0.910, respectively (both p > .05). The HCC-RESCUE score accurately predicted HCC risk in Caucasian CHB patients under entecavir or tenofovir therapy. A substantial proportion of patients can be dropped from HCC surveillance by using the HCC-RESCUE score.
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Affiliation(s)
- Fatih Güzelbulut
- Department of Gastroenterology, Haydarpaşa Numune Training and Research Hospital, University of Health Sciences Turkey, Istanbul, Turkey
| | - Pınar Gökçen
- Department of Gastroenterology, Ümraniye Training and Research Hospital, University of Health Sciences Turkey, Istanbul, Turkey
| | - Güray Can
- Faculty of Medicine, Department of Gastroenterology, Abant Izzet Baysal University, Bolu, Turkey
| | - Gupse Adalı
- Department of Gastroenterology, Ümraniye Training and Research Hospital, University of Health Sciences Turkey, Istanbul, Turkey
| | - Ayça Gökçen Değirmenci Saltürk
- Department of Gastroenterology, Haydarpaşa Numune Training and Research Hospital, University of Health Sciences Turkey, Istanbul, Turkey
| | - Özgür Bahadır
- Department of Gastroenterology, Haydarpaşa Numune Training and Research Hospital, University of Health Sciences Turkey, Istanbul, Turkey
| | - Kamil Özdil
- Department of Gastroenterology, Ümraniye Training and Research Hospital, University of Health Sciences Turkey, Istanbul, Turkey
| | - Hamdi Levent Doğanay
- Department of Gastroenterology, Ümraniye Training and Research Hospital, University of Health Sciences Turkey, Istanbul, Turkey
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26
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Kim SU, Chon YE, Seo YS, Lee HW, Lee HA, Kim MN, Min IK, Park JY, Kim DY, Ahn SH, Tak WY, Kim BK, Park SY. A multi-centre study of trends in hepatitis B virus-related hepatocellular carcinoma risk over time during long-term entecavir therapy. J Viral Hepat 2020; 27:1352-1358. [PMID: 32852880 DOI: 10.1111/jvh.13384] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 06/22/2020] [Accepted: 06/28/2020] [Indexed: 12/13/2022]
Abstract
The risk of developing hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is reduced by antiviral therapy. Here, we evaluated the chronological trends in HCC development risk starting in 2007, when entecavir reimbursement was first initiated in South Korea. Treatment-naïve patients with chronic hepatitis B (CHB) receiving entecavir 0.5 mg/d were stratified into three groups according to entecavir start time: early (2007-2010), middle (2011-2012) and late (2013-2014) cohorts Among 2442 patients, cumulative probabilities of developing HCC after 1, 3 and 5 years were, respectively, 1.7%, 5.1%, and 8.2% (early cohort; n = 672); 1.5%, 5.1% and 8.9% (middle cohort; n = 757); and 1.2%, 5.3% and 10.6% (late cohort; n = 1013; P > .05 between each pair). Older age, male, positive hepatitis B e antigen, liver cirrhosis, Child-Pugh class B (vs A) and lower platelet count significantly predicted HCC development in univariate analysis (P < .001), whereas entecavir start time (early vs middle vs late cohorts) did not affect the risk of HCC development (P = .457). A multivariate analysis revealed that older age (adjusted hazard ratio [aHR]=1.041), male gender (aHR = 2.069), liver cirrhosis (aHR = 3.771) and Child-Pugh class B (vs A, aHR = 1.548) were independently associated with an increased risk of HCC development, whereas higher platelet count was independently associated with a reduced risk of HCC development (aHR = 0.993; all P < .05). In conclusion, the risk of developing HCC among patients receiving entecavir in South Korea has been stable since 2007. To establish more effective HCC surveillance programs, further studies regarding the carcinogenic roles of nonviral factors are required.
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Affiliation(s)
- Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Yong Eun Chon
- Department of Internal Medicine, Cha Bundang Medical Center, Cha University, Seongnam, Korea
| | - Yeon Seok Seo
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Han Ah Lee
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Mi Na Kim
- Department of Internal Medicine, Cha Bundang Medical Center, Cha University, Seongnam, Korea
| | - In Kyung Min
- Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Won Young Tak
- Department of Internal Medicine, School of Medicine, Kyungpook National University Hospital, Kyungpook National University, Daegu, Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Soo Young Park
- Department of Internal Medicine, School of Medicine, Kyungpook National University Hospital, Kyungpook National University, Daegu, Korea
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27
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Kubota N, Fujiwara N, Hoshida Y. Clinical and Molecular Prediction of Hepatocellular Carcinoma Risk. J Clin Med 2020; 9:jcm9123843. [PMID: 33256232 PMCID: PMC7761278 DOI: 10.3390/jcm9123843] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2020] [Revised: 11/20/2020] [Accepted: 11/23/2020] [Indexed: 02/07/2023] Open
Abstract
Prediction of hepatocellular carcinoma (HCC) risk becomes increasingly important with recently emerging HCC-predisposing conditions, namely non-alcoholic fatty liver disease and cured hepatitis C virus infection. These etiologies are accompanied with a relatively low HCC incidence rate (~1% per year or less), while affecting a large patient population. Hepatitis B virus infection remains a major HCC risk factor, but a majority of the patients are now on antiviral therapy, which substantially lowers, but does not eliminate, HCC risk. Thus, it is critically important to identify a small subset of patients who have elevated likelihood of developing HCC, to optimize the allocation of limited HCC screening resources to those who need it most and enable cost-effective early HCC diagnosis to prolong patient survival. To date, numerous clinical-variable-based HCC risk scores have been developed for specific clinical contexts defined by liver disease etiology, severity, and other factors. In parallel, various molecular features have been reported as potential HCC risk biomarkers, utilizing both tissue and body-fluid specimens. Deep-learning-based risk modeling is an emerging strategy. Although none of them has been widely incorporated in clinical care of liver disease patients yet, some have been undergoing the process of validation and clinical development. In this review, these risk scores and biomarker candidates are overviewed, and strategic issues in their validation and clinical translation are discussed.
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28
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Uchida D, Takaki A, Oyama A, Adachi T, Wada N, Onishi H, Okada H. Oxidative Stress Management in Chronic Liver Diseases and Hepatocellular Carcinoma. Nutrients 2020; 12:nu12061576. [PMID: 32481552 PMCID: PMC7352310 DOI: 10.3390/nu12061576] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Revised: 05/25/2020] [Accepted: 05/26/2020] [Indexed: 12/12/2022] Open
Abstract
Chronic viral hepatitis B and C and non-alcoholic fatty liver disease (NAFLD) have been widely acknowledged to be the leading causes of liver cirrhosis and hepatocellular carcinoma. As anti-viral treatment progresses, the impact of NAFLD is increasing. NAFLD can coexist with chronic viral hepatitis and exacerbate its progression. Oxidative stress has been recognized as a chronic liver disease progression-related and cancer-initiating stress response. However, there are still many unresolved issues concerning oxidative stress, such as the correlation between the natural history of the disease and promising treatment protocols. Recent findings indicate that oxidative stress is also an anti-cancer response that is necessary to kill cancer cells. Oxidative stress might therefore be a cancer-initiating response that should be down regulated in the pre-cancerous stage in patients with risk factors for cancer, while it is an anti-cancer cell response that should not be down regulated in the post-cancerous stage, especially in patients using anti-cancer agents. Antioxidant nutrients should be administered carefully according to the patients’ disease status. In this review, we will highlight these paradoxical effects of oxidative stress in chronic liver diseases, pre- and post-carcinogenesis.
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