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Franzè MS, Saitta C, Lombardo D, Musolino C, Caccamo G, Filomia R, Pitrone C, Cacciola I, Pollicino T, Raimondo G. Long-term virological and clinical evaluation of chronic hepatitis B patients under nucleos(t)ide analogues therapy. Clin Res Hepatol Gastroenterol 2025; 49:102566. [PMID: 40043798 DOI: 10.1016/j.clinre.2025.102566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Accepted: 03/02/2025] [Indexed: 04/06/2025]
Abstract
INTRODUCTION AND OBJECTIVES Identifying hepatitis B virus (HBV) patients eligible for safe nucleos(t)ide analogues (NAs) discontinuation remains challenging. Discrepant data on combined HBV DNA and quantitative HBV surface antigen (qHBsAg) assessments are available. This study aimed to identify potential predictors for safe treatment discontinuation by evaluating clinical/virological outcomes in patients on long-term NA therapy. PATIENTS AND METHODS A retrospective cohort of 139 chronic hepatitis B (CHB) patients - who consecutively started Entecavir or Tenofovir from 2007 to 2011 - was evaluated. The study population was selected based on anti-HBe positivity, absence of prior antiviral treatment, absence of non-HBV-related liver diseases or hepatocellular carcinoma (HCC), and long-term clinical/ultrasonographic/laboratory evaluations post-NA initiation. Serum samples collected before starting NA (T0) and over ten years (T1-T10) were tested for HBV DNA and qHBsAg. RESULTS Twenty-two/139 (15.8 %) CHB patients (12 chronic hepatitis, 10 cirrhosis) met the inclusion criteria. All patients showed a significant decrease in liver stiffness values in the ten years of follow-up (p = 0.001), and no hepatic decompensation occurred. Three/22 (13.6 %) patients developed HCC. Ten/22 patients (45.5 %; group-A) had fluctuating HBV DNA, while other 10/22 (45.5 %; group-B) showed undetectable HBV DNA for 5-9 years with more significant qHBsAg decline (p = 0.04) than group-A. Two/22 (9.1 %) patients showed a critical qHBsAg decline up to seroconversion together with undetectable HBV DNA. CONCLUSIONS Persistent undetectable HBV DNA levels correlate with qHBsAg reduction and the potential HBsAg seroclearance, suggesting that long-term HBV DNA monitoring in NA-treated CHB patients might help identify candidates for treatment discontinuation.
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Affiliation(s)
- Maria Stella Franzè
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Carlo Saitta
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy; Division of Medicine and Hepatology, University Hospital of Messina, Messina, Italy
| | - Daniele Lombardo
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy; Laboratory of Molecular Hepatology, University Hospital of Messina, Messina, Italy
| | - Cristina Musolino
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy; Laboratory of Molecular Hepatology, University Hospital of Messina, Messina, Italy
| | - Gaia Caccamo
- Division of Medicine and Hepatology, University Hospital of Messina, Messina, Italy
| | - Roberto Filomia
- Division of Medicine and Hepatology, University Hospital of Messina, Messina, Italy
| | - Concetta Pitrone
- Division of Medicine and Hepatology, University Hospital of Messina, Messina, Italy
| | - Irene Cacciola
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy; Division of Medicine and Hepatology, University Hospital of Messina, Messina, Italy
| | - Teresa Pollicino
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy; Laboratory of Molecular Hepatology, University Hospital of Messina, Messina, Italy
| | - Giovanni Raimondo
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy; Division of Medicine and Hepatology, University Hospital of Messina, Messina, Italy.
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Ramier C, Protopopescu C, Di Beo V, Parlati L, Marcellin F, Carrat F, Asselah T, Bourlière M, Carrieri P. Behaviour-Based Predictive Scores of Hepatocellular Carcinoma in People With Chronic Hepatitis B (ANRS CO22 HEPATHER). Liver Int 2025; 45:e70065. [PMID: 40087922 PMCID: PMC11909585 DOI: 10.1111/liv.70065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 01/21/2025] [Accepted: 03/05/2025] [Indexed: 03/17/2025]
Abstract
BACKGROUND AND AIMS Early assessment of hepatocellular carcinoma (HCC) risk could improve long-term outcomes in people with chronic hepatitis B virus (HBV) infection. Some existing HCC predictive scores are not easily implementable. We developed easy-to-use HCC predictive scores based on behavioural and routine bio-clinical data in people with chronic HBV infection. METHODS Eight-year follow-up data was analysed from people with chronic HBV infection enrolled in the French ANRS CO22 HEPATHER cohort. Patients were randomly split into two samples (training/testing). A multivariable Cox model for time to HCC was estimated on the training sample. The HCC predictive score was computed by summing the points assigned to model predictors, normalising their coefficients over a 10-year age increment, and rounding to the nearest integer. The Youden index identified the score's optimal risk threshold. Comparisons with existing predictive scores were performed on the testing sample. RESULTS In the study population (N = 4370; 63% of men; 65% of < 50 years old), 56 HCC cases occurred during 25,900 follow-up person-years. Two HCC predictive scores were defined: SADAPTT (daily soft drink consumption, age, hepatitis Delta infection, unhealthy alcohol use, platelet count, heavy tobacco smoking, and HBV treatment) and ADAPTT (the same predictors except for daily soft drink consumption), with ranges 0-13 and 0-14, respectively, and values ≥ 3 indicating a high HCC risk. Their performances were similar to existing scores. CONCLUSIONS We developed two effective behaviour-based HCC predictive scores, implementable in many settings, including primary care and decentralised areas. Further studies are needed to validate these scores in other datasets.
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Affiliation(s)
- Clémence Ramier
- Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Économiques and Sociales de la Santé and Traitement de l'Information MédicaleMarseilleFrance
| | - Camelia Protopopescu
- Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Économiques and Sociales de la Santé and Traitement de l'Information MédicaleMarseilleFrance
| | - Vincent Di Beo
- Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Économiques and Sociales de la Santé and Traitement de l'Information MédicaleMarseilleFrance
| | - Lucia Parlati
- Département d'Hépatologie/AddictologieUniversité de Paris Cité; INSERM U1016, AP‐HP, Hôpital CochinParisFrance
| | - Fabienne Marcellin
- Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Économiques and Sociales de la Santé and Traitement de l'Information MédicaleMarseilleFrance
| | - Fabrice Carrat
- Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique, Sorbonne UniversitéParisFrance
- Hôpital Saint‐Antoine, Unité de Santé Publique, Assistance Publique‐Hôpitaux de Paris (AP‐HP)ParisFrance
| | - Tarik Asselah
- Department of HepatologyCentre de Recherche Sur l'Inflammation, INSERM UMR 1149, Hôpital Beaujon, Université de Paris‐CitéClichyFrance
| | - Marc Bourlière
- Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Économiques and Sociales de la Santé and Traitement de l'Information MédicaleMarseilleFrance
- Département d'hépatologie et GastroentérologieHôpital Saint JosephMarseilleFrance
| | - Patrizia Carrieri
- Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Économiques and Sociales de la Santé and Traitement de l'Information MédicaleMarseilleFrance
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Liu SJ, Zhang X, Yan LJ, Wang HC, Ding ZN, Liu H, Pan GQ, Han CL, Tian BW, Dong ZR, Wang DX, Yan YC, Li T. Comparison of tenofovir versus entecavir for preventing hepatocellular carcinoma in chronic hepatitis B patients: an umbrella review and meta-analysis. J Cancer Res Clin Oncol 2025; 151:77. [PMID: 39934513 PMCID: PMC11814049 DOI: 10.1007/s00432-025-06082-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2024] [Accepted: 01/02/2025] [Indexed: 02/13/2025]
Abstract
There are several meta-analyses about the comparison of tenofovir disoproxil fumarate (TDF) versus entecavir (ETV) for preventing hepatocellular carcinoma in patients with chronic HBV infection published in recent years. However, the conclusions vary considerably. This umbrella review aims to consolidate evidence from various systematic reviews to evaluate differences in hepatocellular carcinoma prevention between two drugs. Systematic searches were conducted using PubMed, Embase, and Web of Science to identify original meta-analyses. Finally, twelve studies were included for quantitative analyses. We found that TDF treatment was associated with a significantly lower risk of HCC than ETV (hazard ratio, 0.80; 95% CI 0.75-0.86, p < 0.05). The lower risk of HCC in patients given TDF compared with ETV persisted in subgroup analyses performed with propensity score-matched cohorts, cirrhosis cohorts, nucleos(t)ide naïve cohorts and Asian cohorts. In the cohorts of non-Asia and patients without cirrhosis, there was no difference exhibited between these two drugs. Subsequent analyses showed TDF treatment was also associated with a lower incidence of death or transplantation than patients receiving ETV. Overall, the preventive effect of these two drugs on HCC has been studied in several published meta-analyses, but few were graded as high-quality evidence, meanwhile, most of which had high overlap. Thus, future researchers should include updated cohorts or conduct prospective RCTs to further explore this issue.
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Affiliation(s)
- Shi-Jia Liu
- Department of General Surgery, Qilu Hospital of Shandong University, 107 West Wen Hua Road, Jinan, 250012, China
| | - Xiao Zhang
- Department of General Surgery, Qilu Hospital of Shandong University, 107 West Wen Hua Road, Jinan, 250012, China
| | - Lun-Jie Yan
- Department of General Surgery, Qilu Hospital of Shandong University, 107 West Wen Hua Road, Jinan, 250012, China
| | - Han-Chao Wang
- Institute for Financial Studies, Shandong University, Jinan, China
| | - Zi-Niu Ding
- Department of General Surgery, Qilu Hospital of Shandong University, 107 West Wen Hua Road, Jinan, 250012, China
| | - Hui Liu
- Department of General Surgery, Qilu Hospital of Shandong University, 107 West Wen Hua Road, Jinan, 250012, China
| | - Guo-Qiang Pan
- Department of General Surgery, Qilu Hospital of Shandong University, 107 West Wen Hua Road, Jinan, 250012, China
| | - Cheng-Long Han
- Department of General Surgery, Qilu Hospital of Shandong University, 107 West Wen Hua Road, Jinan, 250012, China
| | - Bao-Wen Tian
- Department of General Surgery, Qilu Hospital of Shandong University, 107 West Wen Hua Road, Jinan, 250012, China
| | - Zhao-Ru Dong
- Department of General Surgery, Qilu Hospital of Shandong University, 107 West Wen Hua Road, Jinan, 250012, China
| | - Dong-Xu Wang
- Department of General Surgery, Qilu Hospital of Shandong University, 107 West Wen Hua Road, Jinan, 250012, China
| | - Yu-Chuan Yan
- Department of General Surgery, Qilu Hospital of Shandong University, 107 West Wen Hua Road, Jinan, 250012, China.
| | - Tao Li
- Department of General Surgery, Qilu Hospital of Shandong University, 107 West Wen Hua Road, Jinan, 250012, China.
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Yu H, Huang Y, Li M, Jiang H, Yang B, Xi X, Smayi A, Wu B, Yang Y. Prognostic significance of dynamic changes in liver stiffness measurement in patients with chronic hepatitis B and compensated advanced chronic liver disease. J Gastroenterol Hepatol 2024; 39:2169-2181. [PMID: 38946401 DOI: 10.1111/jgh.16673] [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: 03/23/2024] [Revised: 06/07/2024] [Accepted: 06/16/2024] [Indexed: 07/02/2024]
Abstract
BACKGROUND AND AIM Liver stiffness measurements (LSMs) are promising for monitoring disease progression or regression. We assessed the prognostic significance of dynamic changes in LSM over time on liver-related events (LREs) and death in patients with chronic hepatitis B (CHB) and compensated advanced chronic liver disease (cACLD). METHODS This retrospective study included 1272 patients with CHB and cACLD who underwent at least two measurements, including LSM and fibrosis score based on four factors (FIB-4). ΔLSM was defined as [(follow-up LSM - baseline LSM)/baseline LSM × 100]. We recorded LREs and all-cause mortality during a median follow-up time of 46 months. Hazard ratios (HRs) and confidence intervals (CIs) for outcomes were calculated using Cox regression. RESULTS Baseline FIB-4, baseline LSM, ΔFIB-4, ΔLSM, and ΔLSM/year were independently and simultaneously associated with LREs (adjusted HR, 1.04, 95% CI, 1.00-1.07; 1.02, 95% CI, 1.01-1.03; 1.06, 95% CI, 1.03-1.09; 1.96, 95% CI, 1.63-2.35, 1.02, 95% CI, 1.01-1.04, respectively). The baseline LSM combined with the ΔLSM achieved the highest Harrell's C (0.751), integrated AUC (0.776), and time-dependent AUC (0.737) for LREs. Using baseline LSM and ΔLSM, we proposed a risk stratification method to improve clinical applications. The risk proposed stratification based on LSM performed well in terms of prognosis: low risk (n = 390; reference), intermediate risk (n = 446; HR = 3.38), high risk (n = 272; HR = 5.64), and extremely high risk (n = 164; HR = 11.11). CONCLUSIONS Baseline and repeated noninvasive tests measurement allow risk stratification of patients with CHB and cACLD. Combining baseline and dynamic changes in the LSM improves prognostic prediction.
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Affiliation(s)
- Hongsheng Yu
- Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou, 510630, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China
| | - Yinan Huang
- Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou, 510630, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China
| | - Mingkai Li
- Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou, 510630, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China
| | - Hao Jiang
- Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou, 510630, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China
| | - Bilan Yang
- Department of Gastrointestinal Endoscopy Center, The Eighth Affiliated Hospital, Sun Yat-sen University, 518033, Shenzhen, China
| | - Xiaoli Xi
- Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou, 510630, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China
| | - Abdukyamu Smayi
- Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou, 510630, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China
| | - Bin Wu
- Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou, 510630, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China
| | - Yidong Yang
- Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou, 510630, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China
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Mak LY. Disease modifiers and novel markers in hepatitis B virus-related hepatocellular carcinoma. JOURNAL OF LIVER CANCER 2024; 24:145-154. [PMID: 39099070 PMCID: PMC11449577 DOI: 10.17998/jlc.2024.08.03] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Revised: 07/25/2024] [Accepted: 08/03/2024] [Indexed: 08/06/2024]
Abstract
Chronic hepatitis B (CHB) infection is responsible for 40% of the global burden of hepatocellular carcinoma (HCC) with a high case fatality rate. The risk of HCC differs among CHB subjects owing to differences in host and viral factors. Modifiable risk factors include viral load, use of antiviral therapy, co-infection with other hepatotropic viruses, concomitant metabolic dysfunctionassociated steatotic liver disease or diabetes mellitus, environmental exposure, and medication use. Detecting HCC at early stage improves survival, and current practice recommends HCC surveillance among individuals with cirrhosis, family history of HCC, or above an age cut-off. Ultrasonography with or without serum alpha feto-protein (AFP) every 6 months is widely accepted strategy for HCC surveillance. Novel tumor-specific markers, when combined with AFP, improve diagnostic accuracy than AFP alone to detect HCC at an early stage. To predict the risk of HCC, a number of clinical risk scores have been developed but none of them are clinically implemented nor endorsed by clinical practice guidelines. Biomarkers that reflect viral transcriptional activity and degree of liver fibrosis can potentially stratify the risk of HCC, especially among subjects who are already on antiviral therapy. Ongoing exploration of these novel biomarkers is required to confirm their performance characteristics, replicability and practicability.
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Affiliation(s)
- Lung-Yi Mak
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China
- State Key Laboratory of Liver Research, The Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
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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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Guo D, Li J, Zhao P, Mei T, Li K, Zhang Y. The hepatocellular carcinoma risk in patients with HBV-related cirrhosis: a competing risk nomogram based on a 4-year retrospective cohort study. Front Oncol 2024; 14:1398968. [PMID: 38817899 PMCID: PMC11137271 DOI: 10.3389/fonc.2024.1398968] [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: 03/11/2024] [Accepted: 04/24/2024] [Indexed: 06/01/2024] Open
Abstract
Objective The study aimed to build and validate a competitive risk nomogram to predict the cumulative incidence of hepatocellular carcinoma (HCC) for patients with hepatitis B virus (HBV)-related cirrhosis. Methods A total of 1401 HBV-related cirrhosis patients were retrospectively enrolled from January 1, 2011 to December 31, 2014. Application of 20 times imputation dealt with missing data using multiple imputation by chained equations (MICE). The patients were randomly divided into a training set (n = 1017) and a validation set (n = 384) at a ratio of 3:1. A prediction study was carried out using a competing risk model, where the event of interest was HCC and the competing events were death and liver transplantation, and subdistribution hazard ratios (sHRs) with 95% CIs were reported. The multivariate competing risk model was constructed and validated. Results There was a negligible difference between the original database and the 20 imputed datasets. At the end of follow-up, the median follow-up time was 69.9 months (interquartile range: 43.8-86.6). There were 31.5% (442/1401) of the patients who developed HCC, with a 5-year cumulative incidence of 22.9 (95%CI, 20.8%-25.2%). The univariate and multivariate competing risk regression and construction of the nomogram were performed in 20 imputed training datasets. Age, sex, antiviral therapy history, hepatitis B e antigen, alcohol drinking history, and alpha-fetoprotein levels were included in the nomogram. The area under receiver operating characteristic curve values at 12, 24, 36, 60, and 96 months were 0.68, 0.69, 0.70, 0.68, and 0.80, and the Brier scores were 0.30, 0.25, 0.23, 0.21, and 0.20 in the validation set. According to the cumulative incidence function, the nomogram effectively screened out high-risk HCC patients from low-risk patients in the presence of competing events (Fine-Gray test p < 0.001). Conclusion The competitive risk nomogram was allowed to be used for predicting HCC risk in individual patients with liver cirrhosis, taking into account both the association between risk factors and HCC and the modifying effect of competition events on this association.
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Affiliation(s)
- Dandan Guo
- Interventional Therapy Center for Oncology, Beijing You’An Hospital, Capital Medical University, Beijing, China
| | - Jianjun Li
- Interventional Therapy Center for Oncology, Beijing You’An Hospital, Capital Medical University, Beijing, China
| | - Peng Zhao
- Interventional Therapy Center for Oncology, Beijing You’An Hospital, Capital Medical University, Beijing, China
| | - Tingting Mei
- Interventional Therapy Center for Oncology, Beijing You’An Hospital, Capital Medical University, Beijing, China
| | - Kang Li
- Biomedical Information Center, Beijing You’An Hospital, Capital Medical University, Beijing, China
- Beijing Research Center for Respiratory Infectious Diseases, Beijing, China
| | - Yonghong Zhang
- Interventional Therapy Center for Oncology, Beijing You’An Hospital, Capital Medical University, Beijing, China
- Beijing Research Center for Respiratory Infectious Diseases, Beijing, China
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Lin H, Li G, Delamarre A, Ahn SH, Zhang X, Kim BK, Liang LY, Lee HW, Wong GLH, Yuen PC, Chan HLY, Chan SL, Wong VWS, de Lédinghen V, Kim SU, Yip TCF. A Liver Stiffness-Based Etiology-Independent Machine Learning Algorithm to Predict Hepatocellular Carcinoma. Clin Gastroenterol Hepatol 2024; 22:602-610.e7. [PMID: 37993034 DOI: 10.1016/j.cgh.2023.11.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Revised: 10/30/2023] [Accepted: 11/01/2023] [Indexed: 11/24/2023]
Abstract
BACKGROUND & AIMS The existing hepatocellular carcinoma (HCC) risk scores have modest accuracy, and most are specific to chronic hepatitis B infection. In this study, we developed and validated a liver stiffness-based machine learning algorithm (ML) for prediction and risk stratification of HCC in various chronic liver diseases (CLDs). METHODS MLs were trained for prediction of HCC in 5155 adult patients with various CLDs in Korea and further tested in 2 prospective cohorts from Hong Kong (HK) (N = 2732) and Europe (N = 2384). Model performance was assessed according to Harrell's C-index and time-dependent receiver operating characteristic (ROC) curve. RESULTS We developed the SMART-HCC score, a liver stiffness-based ML HCC risk score, with liver stiffness measurement ranked as the most important among 9 clinical features. The Harrell's C-index of the SMART-HCC score in HK and Europe validation cohorts were 0.89 (95% confidence interval, 0.85-0.92) and 0.91 (95% confidence interval, 0.87-0.95), respectively. The area under ROC curves of the SMART-HCC score for HCC in 5 years was ≥0.89 in both validation cohorts. The performance of SMART-HCC score was significantly better than existing HCC risk scores including aMAP score, Toronto HCC risk index, and 7 hepatitis B-related risk scores. Using dual cutoffs of 0.043 and 0.080, the annual HCC incidence was 0.09%-0.11% for low-risk group and 2.54%-4.64% for high-risk group in the HK and Europe validation cohorts. CONCLUSIONS The SMART-HCC score is a useful machine learning-based tool for clinicians to stratify HCC risk in patients with CLDs.
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Affiliation(s)
- Huapeng Lin
- Medical Data Analytics Center, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Guanlin Li
- Medical Data Analytics Center, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Adèle Delamarre
- Hepatology Unit, Hôpital Haut Lévêque, Bordeaux University Hospital, Bordeaux, France; INSERM U1312, Bordeaux University, Bordeaux, France
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea; Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Xinrong Zhang
- Medical Data Analytics Center, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea; Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Lilian Yan Liang
- Medical Data Analytics Center, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea; Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Grace Lai-Hung Wong
- Medical Data Analytics Center, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Pong-Chi Yuen
- Department of Computer Science, Hong Kong Baptist University, Hong Kong
| | - Henry Lik-Yuen Chan
- Medical Data Analytics Center, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong; Union Hospital, Hong Kong
| | - Stephen Lam Chan
- Department of Clinical Oncology, Sir YK Pao Centre for Cancer, The Chinese University of Hong Kong, Hong Kong; State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong
| | - Vincent Wai-Sun Wong
- Medical Data Analytics Center, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Victor de Lédinghen
- Hepatology Unit, Hôpital Haut Lévêque, Bordeaux University Hospital, Bordeaux, France; INSERM U1312, Bordeaux University, Bordeaux, France.
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea; Yonsei Liver Center, Severance Hospital, Seoul, Korea.
| | - Terry Cheuk-Fung Yip
- Medical Data Analytics Center, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong.
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9
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Yim HJ, Kang SH, Jung YK, Ahn SH, Kim W, Yang JM, Jang JY, Kweon YO, Cho YK, Kim YJ, Hong GY, Kim DJ, Sohn JH, Lee JW, Park SJ, Yim SY, Park JK, Um SH. Reduced Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Receiving Long-Term Besifovir Therapy. Cancers (Basel) 2024; 16:887. [PMID: 38473248 DOI: 10.3390/cancers16050887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Revised: 02/14/2024] [Accepted: 02/20/2024] [Indexed: 03/14/2024] Open
Abstract
No information is available regarding the influence of besifovir (BSV), a new nucleotide analogue, on the occurrence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). This study evaluated the reduced risk of HCC in patients undergoing BSV treatment. A total of 188 patients with CHB were treated with BSV for up to 8 years. We prospectively assessed the incidence of HCC compared with the risk from prediction models. During the follow-up, 5 patients developed HCC: 1 of 139 patients with non-cirrhotic CHB, and 4 of 49 patients with liver cirrhosis. We compared the HCC incidence in non-cirrhotic and cirrhotic patients with the predicted number derived from the REACH-B (risk estimation for HCC in CHB) model and GAG-HCC (guide with age, gender, HBV DNA, core promotor mutation, and cirrhosis) model, respectively. The standardized incidence ratio (SIR) was 0.128 (p = 0.039) at 7 years in non-cirrhotic CHB patients, and the SIR was 0.371 (p = 0.047) at 7.5 years in cirrhotic patients, suggesting a significantly decreased HCC incidence in both groups. HCC prediction was available for BSV-treated patients using existing models. In conclusion, BSV decreased the risk of HCC in patients with CHB, and prediction models were applicable. Clinical trial registry website and trial number: ClinicalTrials.gov no: NCT01937806.
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Affiliation(s)
- Hyung Joon Yim
- Department of Internal Medicine, Korea University Ansan Hospital, 123, Jeokgeum-ro, Danwon-gu, Ansan 15355, Republic of Korea
| | - Seong Hee Kang
- Department of Internal Medicine, Korea University Ansan Hospital, 123, Jeokgeum-ro, Danwon-gu, Ansan 15355, Republic of Korea
| | - Young Kul Jung
- Department of Internal Medicine, Korea University Ansan Hospital, 123, Jeokgeum-ro, Danwon-gu, Ansan 15355, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea
| | - Won Kim
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, 20 Boramae-ro 5-gil, Dongjak-gu, Seoul 07061, Republic of Korea
| | - Jin Mo Yang
- Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, 93 Jungbu-daero, Paldal-gu, Suwon 16247, Republic of Korea
| | - Jae Young Jang
- Department of Internal Medicine, Soonchunhyang University Seoul Hospital, 59, Daesagwan-ro, Yongsan-gu, Seoul 04401, Republic of Korea
| | - Yong Oh Kweon
- Department of Internal Medicine, Kyungpook National University Hospital, 680 gukchaebosang-ro, Jung-gu, Daegu 41944, Republic of Korea
| | - Yong Kyun Cho
- Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul 03181, Republic of Korea
| | - Yoon Jun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea
| | - Gun Young Hong
- Department of Internal Medicine, Kwangju Christian Hospital, 37 Yangnim-ro, Nam-gu, Gwangju 61661, Republic of Korea
| | - Dong Joon Kim
- Department of Internal Medicine and Center for Liver and Digestive Diseases, Hallym University Chuncheon Sacred Heart Hospital, 77 Sakju-ro, Chuncheon 24253, Republic of Korea
| | - Joo Hyun Sohn
- Department of Internal Medicine, Hanyang University Guri Hospital, 153, Gyeongchun-ro, Guri-si 11923, Republic of Korea
| | - Jin Woo Lee
- Department of Internal Medicine, Inha University Hospital, 27 Inhang-ro, Jung-gu, Incheon 22332, Republic of Korea
| | - Sung Jae Park
- Department of Internal Medicine, Inje University Busan Paik Hospital, 75 Bokji-ro, Busanjin-gu, Busan 47392, Republic of Korea
| | - Sun Young Yim
- Department of Internal Medicine, Korea University Anam Hospital, 73 Goryeodae-ro, Seongbuk-gu, Seoul 02841, Republic of Korea
| | - Jin Kyung Park
- Ildong Pharmaceutical Company, 2, Baumoe-ro 27-gil, Seocho-gu, Seoul 06752, Republic of Korea
| | - Soon Ho Um
- Department of Internal Medicine, Korea University Anam Hospital, 73 Goryeodae-ro, Seongbuk-gu, Seoul 02841, Republic of Korea
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10
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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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11
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Ha Y, Lim J, Chon YE, Kim MN, Lee JH, Kim KM, Shim JH, Lee D, Hwang SG, Han S, Lee HC. Five-year on-treatment variables-based PPACS model predicts subsequent hepatocellular carcinoma in entecavir/tenofovir-treated patients. Int J Cancer 2023; 153:2045-2054. [PMID: 37615539 DOI: 10.1002/ijc.34704] [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: 03/19/2023] [Revised: 08/01/2023] [Accepted: 08/03/2023] [Indexed: 08/25/2023]
Abstract
Considering the lower risk of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients receiving long-term potent antiviral therapy, models predicting HCC after 5 years of therapy are needed. We conducted a multicenter retrospective cohort study to construct and validate a model predicting HCC after 5 years of entecavir (ETV) or tenofovir (TFV) therapy for CHB. The endpoint was HCC after 5 years of ETV/TFV therapy. Information on age, sex, liver cirrhosis (assessed by diagnosis code and confirmed by clinical findings) and type of antiviral agent was obtained at baseline (initiation of ETV/TFV). Laboratory values were collected at baseline and 5 years. Risk factors for HCC were identified in the training set and the final prediction model was validated using the test set. Among 7542 patients, 345 (4.6%) developed HCC after 5 years of ETV/TFV therapy. HCC risk after 5 years of ETV/TFV therapy was increased by 4-fold in patients with liver cirrhosis than in those without cirrhosis at baseline. Furthermore, Platelet counts and Prothrombin time at 5 years, Age at baseline and Sex were associated with risk of HCC and were incorporated into a prediction model, PPACS. PPACS showed a good performance with a time-dependent area under the curve of 0.80 (95% confidence interval, 0.75-0.85) at 8-year of ETV/TFV therapy, a Brier score of 0.031 and an integrated Brier score of 0.006 in the test set. In conclusion, the PPACS model provides a reliable assessment of HCC risk after 5 years of ETV/TFV therapy (https://ppacs.shinyapps.io/shiny_app_up/).
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Affiliation(s)
- Yeonjung Ha
- Department of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam-si, South Korea
| | - Jihye Lim
- Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Young Eun Chon
- Department of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam-si, South Korea
| | - Mi Na Kim
- Department of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam-si, South Korea
| | - Joo Ho Lee
- Department of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam-si, South Korea
| | - Kang Mo Kim
- Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Ju Hyun Shim
- Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Danbi Lee
- Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Seong Gyu Hwang
- Department of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam-si, South Korea
| | - Seungbong Han
- Department of Biostatistics, Korea University College of Medicine, Seoul, South Korea
| | - Han Chu Lee
- Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
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12
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Huang DQ, Singal AG, Kanwal F, Lampertico P, Buti M, Sirlin CB, Nguyen MH, Loomba R. Hepatocellular carcinoma surveillance - utilization, barriers and the impact of changing aetiology. Nat Rev Gastroenterol Hepatol 2023; 20:797-809. [PMID: 37537332 DOI: 10.1038/s41575-023-00818-8] [Citation(s) in RCA: 79] [Impact Index Per Article: 39.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/30/2023] [Indexed: 08/05/2023]
Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. Surveillance for HCC is critical for early detection and treatment, but fewer than one-quarter of individuals at risk of HCC undergo surveillance. Multiple failures across the screening process contribute to the underutilization of surveillance, including limited disease awareness among patients and health-care providers, knowledge gaps, and difficulty recognizing patients who are at risk. Non-alcoholic fatty liver disease and alcohol-associated liver disease are the fastest-rising causes of HCC-related death worldwide and are associated with unique barriers to surveillance. In particular, more than one-third of patients with HCC related to non-alcoholic fatty liver disease do not have cirrhosis and therefore lack a routine indication for HCC surveillance on the basis of current practice guidelines. Semi-annual abdominal ultrasound with measurement of α-fetoprotein levels is recommended for HCC surveillance, but the sensitivity of this approach for early HCC is limited, especially for patients with cirrhosis or obesity. In this Review, we discuss the current status of HCC surveillance and the remaining challenges, including the changing aetiology of liver disease. We also discuss strategies to improve the utilization and quality of surveillance for HCC.
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Affiliation(s)
- Daniel Q Huang
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore.
| | - Amit G Singal
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Fasiha Kanwal
- Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
| | - Pietro Lampertico
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy
- CRC "A. M. and A. Migliavacca" Center for Liver Disease, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Maria Buti
- Liver Unit, Department of Internal Medicine, Hospital Universitari Valle d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
- CIBER-EHD del Instituto Carlos III, Barcelona, Spain
| | - Claude B Sirlin
- Liver Imaging Group, Department of Radiology, UCSD School of Medicine, San Diego, CA, USA
| | - Mindie H Nguyen
- Department of Epidemiology and Population Health, Stanford University Medical Center, Stanford University, Palo Alto, CA, USA
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford University, Palo Alto, CA, USA
| | - Rohit Loomba
- NAFLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, San Diego, CA, USA
- Division of Epidemiology, Department of Family Medicine and Public Health, University of California at San Diego, San Diego, CA, USA
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13
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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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14
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Wang Q, Guo D, Gao W, Yuan C, Li J, Zhang Y, He N, Zhao P, Zheng J, Zhang Y. Individual surveillance by competing risk model for patients with hepatocellular carcinoma occurrence in all-cause cirrhosis. J Cancer Res Clin Oncol 2023; 149:13403-13416. [PMID: 37495731 PMCID: PMC10587216 DOI: 10.1007/s00432-023-04911-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Accepted: 05/20/2023] [Indexed: 07/28/2023]
Abstract
PURPOSE It was of great significance to identify someone with a high risk of hepatocellular carcinoma (HCC) occurrence and make a diagnosis as early as possible. Therefore, we aimed to develop and validate a new, objective, and accurate prediction model, and convert it into a nomogram to make a personalized prediction of cancer occurrence in cirrhotic patients with different etiologies. METHODS The present study included 938 patients with cirrhosis from January 1, 2011, to December 31, 2012. Patients were prospectively followed-up until January 1, 2018. We used a competing risk model and the Fine-Gray test to develop and validate the prediction model and to plot a nomogram based on the model established. RESULTS At the end of follow-up, 202 (21.5%) patients developed HCC, with a 5-year incidence of 19.0% (corrected for competing risk model). Based on the competing risk regression method, we built a prediction model including age, gender, etiology, lymphocyte, and A/G ratio. Three groups with different risks were generated on account of tertiles of the 5-year risk predicted by the model. The cumulative 1-, 3-, and 5-year incidences of HCC were 2.0%, 20.8%, and 42.3% in high-risk group, 0.9%, 10.1%, and 17.7% in medium-risk group, and 0%, 2.0%, 8.5% in low-risk group (P < 0.001). The model showed excellent discrimination and calibration in predicting the risk of HCC occurrence in patients with all-cause cirrhosis. CONCLUSION The model could make an individual prediction of cancer occurrence and stratify patients based on predicted risk, regardless of the causes of cirrhosis.
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Affiliation(s)
- Qi Wang
- Research Center for Biomedical Resources, Beijing You'an Hospital, Capital Medical University, Beijing, 100069, China
| | - Dandan Guo
- Interventional Therapy Center for Oncology, Beijing You'an Hospital, Capital Medical University, Beijing, 100069, China
| | - Wenfeng Gao
- Interventional Therapy Center for Oncology, Beijing You'an Hospital, Capital Medical University, Beijing, 100069, China
| | - Chunwang Yuan
- Interventional Therapy Center for Oncology, Beijing You'an Hospital, Capital Medical University, Beijing, 100069, China
| | - Jianjun Li
- Interventional Therapy Center for Oncology, Beijing You'an Hospital, Capital Medical University, Beijing, 100069, China
| | - Yinghua Zhang
- Interventional Therapy Center for Oncology, Beijing You'an Hospital, Capital Medical University, Beijing, 100069, China
| | - Ning He
- Interventional Therapy Center for Oncology, Beijing You'an Hospital, Capital Medical University, Beijing, 100069, China
| | - Peng Zhao
- Interventional Therapy Center for Oncology, Beijing You'an Hospital, Capital Medical University, Beijing, 100069, China
| | - Jiasheng Zheng
- Interventional Therapy Center for Oncology, Beijing You'an Hospital, Capital Medical University, Beijing, 100069, China
| | - Yonghong Zhang
- Interventional Therapy Center for Oncology, Beijing You'an Hospital, Capital Medical University, Beijing, 100069, China.
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15
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Xu X, Jiang L, Zeng Y, Pan L, Lou Z, Ruan B. HCC prediction models in chronic hepatitis B patients receiving entecavir or tenofovir: a systematic review and meta-analysis. Virol J 2023; 20:180. [PMID: 37582759 PMCID: PMC10428529 DOI: 10.1186/s12985-023-02145-5] [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: 02/21/2023] [Accepted: 07/28/2023] [Indexed: 08/17/2023] Open
Abstract
BACKGROUND Our study aimed to compare the predictive performance of different hepatocellular carcinoma (HCC) prediction models in chronic hepatitis B patients receiving entecavir or tenofovir, including discrimination, calibration, negative predictive value (NPV) in low-risk, and proportion of low-risk. METHODS We conducted a systematic literature research in PubMed, EMbase, the Cochrane Library, and Web of Science before January 13, 2022. The predictive performance was assessed by area under receiver operating characteristic curve (AUROC), calibration index, negative predictive value, and the proportion in low-risk. Subgroup and meta-regression analyses of discrimination and calibration were conducted. Sensitivity analysis was conducted to validate the stability of the results. RESULTS We identified ten prediction models in 23 studies. The pooled 3-, 5-, and 10-year AUROC varied from 0.72 to 0.84, 0.74 to 0.83, and 0.76 to 0.86, respectively. REAL-B, AASL-HCC, and HCC-RESCUE achieved the best discrimination. HCC-RESCUE, PAGE-B, and mPAGE-B overestimated HCC development, whereas mREACH-B, AASL-HCC, REAL-B, CAMD, CAGE-B, SAGE-B, and aMAP underestimated it. All models were able to identify people with a low risk of HCC accurately. HCC-RESCUE and aMAP recognized over half of the population as low-risk. Subgroup analysis and sensitivity analysis showed similar results. CONCLUSION Considering the predictive performance of all four aspects, we suggest that HCC-RESCUE was the best model to utilize in clinical practice, especially in primary care and low-income areas. To confirm our findings, further validation studies with the above four components were required.
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Affiliation(s)
- Xiaolan Xu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, National Medical Center for Infectious Diseases, Zhejiang University School of Medicine, 79 Qingchun Road, Shangcheng District, Hangzhou, 310000, China
- Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, 310000, China
| | - Lushun Jiang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, National Medical Center for Infectious Diseases, Zhejiang University School of Medicine, 79 Qingchun Road, Shangcheng District, Hangzhou, 310000, China
| | - Yifan Zeng
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, National Medical Center for Infectious Diseases, Zhejiang University School of Medicine, 79 Qingchun Road, Shangcheng District, Hangzhou, 310000, China
| | - Liya Pan
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, National Medical Center for Infectious Diseases, Zhejiang University School of Medicine, 79 Qingchun Road, Shangcheng District, Hangzhou, 310000, China
| | - Zhuoqi Lou
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, National Medical Center for Infectious Diseases, Zhejiang University School of Medicine, 79 Qingchun Road, Shangcheng District, Hangzhou, 310000, China
| | - Bing Ruan
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, National Medical Center for Infectious Diseases, Zhejiang University School of Medicine, 79 Qingchun Road, Shangcheng District, Hangzhou, 310000, China.
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16
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Lee HW, Kim H, Park T, Park SY, Chon YE, Seo YS, Lee JS, Park JY, Kim DY, Ahn SH, Kim BK, Kim SU. A machine learning model for predicting hepatocellular carcinoma risk in patients with chronic hepatitis B. Liver Int 2023; 43:1813-1821. [PMID: 37452503 DOI: 10.1111/liv.15597] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 04/17/2023] [Accepted: 04/19/2023] [Indexed: 07/18/2023]
Abstract
BACKGROUND Machine learning (ML) algorithms can be used to overcome the prognostic performance limitations of conventional hepatocellular carcinoma (HCC) risk models. We established and validated an ML-based HCC predictive model optimized for patients with chronic hepatitis B (CHB) infections receiving antiviral therapy (AVT). METHODS Treatment-naïve CHB patients who were started entecavir (ETV) or tenofovir disoproxil fumarate (TDF) were enrolled. We used a training cohort (n = 960) to develop a novel ML model that predicted HCC development within 5 years and validated the model using an independent external cohort (n = 1937). ML algorithms consider all potential interactions and do not use predefined hypotheses. RESULTS The mean age of the patients in the training cohort was 48 years, and most patients (68.9%) were men. During the median 59.3 (interquartile range 45.8-72.3) months of follow-up, 69 (7.2%) patients developed HCC. Our ML-based HCC risk prediction model had an area under the receiver-operating characteristic curve (AUC) of 0.900, which was better than the AUCs of CAMD (0.778) and REAL B (0.772) (both p < .05). The better performance of our model was maintained (AUC = 0.872 vs. 0.788 for CAMD and 0.801 for REAL B) in the validation cohort. Using cut-off probabilities of 0.3 and 0.5, the cumulative incidence of HCC development differed significantly among the three risk groups (p < .001). CONCLUSIONS Our new ML model performed better than models in terms of predicting the risk of HCC development in CHB patients receiving AVT.
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Affiliation(s)
- Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Hwiyoung Kim
- Department of Biomedical Systems Informatics, Center for Clinical Imaging Data Science (CCIDS), Yonsei University College of Medicine, Seoul, Republic of Korea
- Department of Artificial Intelligence, Yonsei University, College of Medicine, Seoul, Republic of Korea
| | - Taeyun Park
- Department of Artificial Intelligence, Yonsei University, College of Medicine, Seoul, Republic of Korea
| | - Soo Young Park
- Department of Internal medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea
| | - Young Eun Chon
- Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Bundang, Republic of Korea
| | - Yeon Seok Seo
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Jae Seung Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
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Wu X, Xu X, Zhou J, Sun Y, Ding H, Xie W, Chen G, Ma A, Piao H, Wang B, Chen S, Meng T, Ou X, Yang HI, Jia J, Kong Y, You H. Hepatocellular carcinoma prediction model performance decreases with long-term antiviral therapy in chronic hepatitis B patients. Clin Mol Hepatol 2023; 29:747-762. [PMID: 37165622 PMCID: PMC10366790 DOI: 10.3350/cmh.2023.0121] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 05/04/2023] [Accepted: 05/10/2023] [Indexed: 05/12/2023] Open
Abstract
BACKGROUND/AIMS Existing hepatocellular carcinoma (HCC) prediction models are derived mainly from pretreatment or early on-treatment parameters. We reassessed the dynamic changes in the performance of 17 HCC models in patients with chronic hepatitis B (CHB) during long-term antiviral therapy (AVT). METHODS Among 987 CHB patients administered long-term entecavir therapy, 660 patients had 8 years of follow-up data. Model scores were calculated using on-treatment values at 2.5, 3, 3.5, 4, 4.5, and 5 years of AVT to predict threeyear HCC occurrence. Model performance was assessed with the area under the receiver operating curve (AUROC). The original model cutoffs to distinguish different levels of HCC risk were evaluated by the log-rank test. RESULTS The AUROCs of the 17 HCC models varied from 0.51 to 0.78 when using on-treatment scores from years 2.5 to 5. Models with a cirrhosis variable showed numerically higher AUROCs (pooled at 0.65-0.73 for treated, untreated, or mixed treatment models) than models without (treated or mixed models: 0.61-0.68; untreated models: 0.51-0.59). Stratification into low, intermediate, and high-risk levels using the original cutoff values could no longer reflect the true HCC incidence using scores after 3.5 years of AVT for models without cirrhosis and after 4 years of AVT for models with cirrhosis. CONCLUSION The performance of existing HCC prediction models, especially models without the cirrhosis variable, decreased in CHB patients on long-term AVT. The optimization of existing models or the development of novel models for better HCC prediction during long-term AVT is warranted.
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Affiliation(s)
- Xiaoning Wu
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing, Mainland of China
| | - Xiaoqian Xu
- Clinical Epidemiology and EBM Unit, Beijing Friendship Hospital, Capital Medical University, Beijing Clinical Research Institute, Beijing, Mainland of China
| | - Jialing Zhou
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing, Mainland of China
| | - Yameng Sun
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing, Mainland of China
| | - Huiguo Ding
- Department of Gastroenterology, Beijing Youan Hospital, Capital Medical University, Beijing, Mainland of China
| | - Wen Xie
- Liver Research Center, Beijing Ditan Hospital, Capital Medical University, Beijing, Mainland of China
| | - Guofeng Chen
- Division of Liver Fibrosis, The Fifth Medical Center, General Hospital of the People’s Liberation Army, Beijing, Mainland of China
| | - Anlin Ma
- Division of Infectious Diseases, China-Japan Friendship Hospital, Beijing, Mainland of China
| | - Hongxin Piao
- Office of Clinical Trials, Affiliated Hospital of Yanbian University, Jilin, Mainland of China
| | - Bingqiong Wang
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing, Mainland of China
| | - Shuyan Chen
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing, Mainland of China
| | - Tongtong Meng
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing, Mainland of China
| | - Xiaojuan Ou
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing, Mainland of China
| | - Hwai-I Yang
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing, Mainland of China
| | - Yuanyuan Kong
- Clinical Epidemiology and EBM Unit, Beijing Friendship Hospital, Capital Medical University, Beijing Clinical Research Institute, Beijing, Mainland of China
| | - Hong You
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing, Mainland of China
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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: 61] [Impact Index Per Article: 30.5] [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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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, China HepB Related Fibrosis Assessment Research Group. 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 JS, Lim TS, Lee HW, Kim SU, Park JY, Kim DY, Ahn SH, Lee HW, Lee JI, Kim JK, Min IK, Kim BK. Suboptimal Performance of Hepatocellular Carcinoma Prediction Models in Patients with Hepatitis B Virus-Related Cirrhosis. Diagnostics (Basel) 2022; 13:3. [PMID: 36611295 PMCID: PMC9818663 DOI: 10.3390/diagnostics13010003] [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: 11/01/2022] [Revised: 12/14/2022] [Accepted: 12/14/2022] [Indexed: 12/24/2022] Open
Abstract
This study aimed to evaluate the predictive performance of pre-existing well-validated hepatocellular carcinoma (HCC) prediction models, established in patients with HBV-related cirrhosis who started potent antiviral therapy (AVT). We retrospectively reviewed the cases of 1339 treatment-naïve patients with HBV-related cirrhosis who started AVT (median period, 56.8 months). The scores of the pre-existing HCC risk prediction models were calculated at the time of AVT initiation. HCC developed in 211 patients (15.1%), and the cumulative probability of HCC development at 5 years was 14.6%. Multivariate Cox regression analysis revealed that older age (adjusted hazard ratio [aHR], 1.023), lower platelet count (aHR, 0.997), lower serum albumin level (aHR, 0.578), and greater LS value (aHR, 1.012) were associated with HCC development. Harrell’s c-indices of the PAGE-B, modified PAGE-B, modified REACH-B, CAMD, aMAP, HCC-RESCUE, AASL-HCC, Toronto HCC Risk Index, PLAN-B, APA-B, CAGE-B, and SAGE-B models were suboptimal in patients with HBV-related cirrhosis, ranging from 0.565 to 0.667. Nevertheless, almost all patients were well stratified into low-, intermediate-, or high-risk groups according to each model (all log-rank p < 0.05), except for HCC-RESCUE (p = 0.080). Since all low-risk patients had cirrhosis at baseline, they had unneglectable cumulative incidence of HCC development (5-year incidence, 4.9−7.5%). Pre-existing risk prediction models for patients with chronic hepatitis B showed suboptimal predictive performances for the assessment of HCC development in patients with HBV-related cirrhosis.
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Affiliation(s)
- Jae Seung Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Republic of Korea
| | - Tae Seop Lim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Division of Gastroenterology, Department of Internal Medicine, Yongin Severance Hospital, Yonsei University Health System, Gyeonggi-do, Seoul 03722, Republic of Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Republic of Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Republic of Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Republic of Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Republic of Korea
| | - Hyun Woong Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Division of Gastroenterology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University Health System, Seoul 06273, Republic of Korea
| | - Jung Il Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Division of Gastroenterology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University Health System, Seoul 06273, Republic of Korea
| | - Ja Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Division of Gastroenterology, Department of Internal Medicine, Yongin Severance Hospital, Yonsei University Health System, Gyeonggi-do, Seoul 03722, Republic of Korea
| | - In Kyung Min
- Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Republic of Korea
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A Mac-2 Binding Protein Glycosylation Isomer-Based Risk Model Predicts Hepatocellular Carcinoma in HBV-Related Cirrhotic Patients on Antiviral Therapy. Cancers (Basel) 2022; 14:cancers14205063. [PMID: 36291847 PMCID: PMC9599873 DOI: 10.3390/cancers14205063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 10/13/2022] [Accepted: 10/14/2022] [Indexed: 11/17/2022] Open
Abstract
Mac-2 binding protein glycosylation isomer (M2BPGi) has not been used in a risk score to predict hepatocellular carcinoma (HCC). We enrolled 1003 patients with chronic hepatitis B and cirrhosis receiving entecavir or tenofovir therapy for more than12 months to construct an HCC risk score. In the development cohort, Cox regression analysis identified male gender, age, platelet count, AFP and M2BPGi levels at 12 months of treatment as independent risk factors of HCC. We developed the HCC risk prediction model, the ASPAM-B score, based on age, sex, platelet count, AFP and M2BPGi levels at 12 months of treatment, with the total scores ranging from 0 to 11.5. This risk model accurately classified patients into low (0−3.5), medium (4−7), and high (>7) risk in the development and validation groups (p < 0.001). The areas under the receiver operating characteristic curve (AUROC) of 3-, 5- and 9-year risks of HCC were 0.742, 0.728 and 0.719, respectively, in the development cohort. All AUROC between the ASPAM-B and APA-B, PAGE-B, RWS-HCC and THRI scores at 3−9 years were significantly different. The M2BPGi-based risk model exhibited good discriminant function in predicting HCC in cirrhotic patients who received long-term antiviral treatment.
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22
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Cheng R, Xu X. Validation of Hepatocellular Carcinoma Risk Prediction Models in Patients with Hepatitis B-Related Cirrhosis. J Hepatocell Carcinoma 2022; 9:987-997. [PMID: 36117526 PMCID: PMC9480598 DOI: 10.2147/jhc.s377435] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Accepted: 09/06/2022] [Indexed: 12/24/2022] Open
Abstract
Purpose Several risk models have been developed to predict the hepatocellular carcinoma (HCC) risk in patients with chronic hepatitis B (CHB); however, it remains unclear whether these models are useful for risk assessment in patients with hepatitis B virus (HBV)-related cirrhosis undergoing antiviral therapy. Patients and Methods A total of 252 treatment-naive cirrhosis patients with no history of HCC who underwent treatment with nucleos(t)ide analogues between January 2010 and July 2014 were enrolled. Cox proportional hazards model was used to analyze the risk factors for HCC. "TimeROC" and "survival ROC" package, written for R, were used to compare the time-dependent area under the receiver operating characteristic (AUROC) curves for the predictability of the HCC risk scores. Results During the mean follow-up period of 56.96 months, 48 (19.0%) patients developed HCC. Cox multivariate stepwise regression analysis revealed that international normalized ratio (hazard ratio [HR] 2.771, 95% confidence interval [CI] 1.462-5.254; P=0.002), alpha-fetoprotein (HR 1.001, 95% CI 1.000-1.003; P=0.035), diabetes mellitus (HR 3.061, 95% CI 1.542-6.077; P=0.001), and alcohol intake (HR 2.250, 95% CI 1.042-4.856; P=0.039) were independent indicators of the HCC risk. AUROC at 3 (0.739) and 5 years (0.695) for the REAL-B score were consistently higher than those of the other risk models except RWS-HCC. The time-dependent AUROC value at 1 year for the REAL-B score was similar to those of the other risk models. According to REAL-B score stratification (0-3, low; 4-7, moderate; and 8-13, high), the HCC risk rates at 1, 3, and 5 years were 2.4%, 5.6%, and 9.0% in the intermediate-risk group, and 7.2%, 21.1%, and 26.3% in the high-risk group, respectively (all P<0.001 between each pair). Conclusion REAL-B score showed a persistently high prognostic capability in predicting the HCC risk in HBV-related cirrhosis patients undergoing antiviral therapy.
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Affiliation(s)
- Ran Cheng
- Department of Infectious Diseases, Peking University Third Hospital, Beijing, People's Republic of China
| | - Xiaoyuan Xu
- Department of Gastroenterology, Peking University First Hospital, Beijing, People's Republic of China
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Moving Away From a One-Size-Fits-All Approach to Hepatocellular Carcinoma Surveillance. Am J Gastroenterol 2022; 117:1409-1411. [PMID: 35973179 DOI: 10.14309/ajg.0000000000001897] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 06/20/2022] [Indexed: 12/11/2022]
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Comparative Performance of 14 HCC Prediction Models in CHB: A Dynamic Validation at Serial On-Treatment Timepoints. Am J Gastroenterol 2022; 117:1444-1453. [PMID: 35973147 DOI: 10.14309/ajg.0000000000001865] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Accepted: 05/27/2022] [Indexed: 12/11/2022]
Abstract
INTRODUCTION To assess comparative performance of 14 hepatocellular carcinoma (HCC) prediction models in chronic hepatitis B (CHB) patients using on-treatment values at different timepoints. METHODS Based on a nationwide prospective cohort of 986 treatment-naive CHB patients undergoing entecavir therapy with every 26-week follow-up, 14 HCC risk scores were calculated using on-treatment values at week 26, 52, 78, and 104, respectively. Model performance predicting 3-year HCC was assessed using time-dependent area under the receiver operating characteristic curve (AUC) and calibration index. Model cutoffs were validated through common diagnostic accuracy measures. RESULTS During median 4.7-year follow-up, 56 (7.5%) developed HCC. Discrimination using on-treatment values within first 2 years was generally acceptable for most models (AUCs ranging from 0.68 to 0.81), except for REACH-B, NGM-HCC, and PAGE-B, although AUCs slightly decreased from week 26 to 104. Of these, REAL-B, CAMD, GAG-HCC, AASL-HCC, LSM-HCC, mPAGE-B, and mREACH-BII showed highest discrimination with AUCs ranging from 0.76 to 0.81, 0.72 to 0.76, 0.70 to 0.76, and 0.71 to 0.74 when reassessment at week 26, 52, 78, and 104, respectively. With reassessment within first 2 years, both REAL-B and CAMD calibrated well (Brier score ranging from 0.037 to 0.052). Of 9 models reporting cutoffs, REAL-B, AASL-HCC, and mPAGE-B using on-treatment values could identify 30%-40% of patients as low risk with minimal HCC incidence in the low-risk group (0.40% [REAL-B]-1.56% [mPAGE-B]). DISCUSSION In this undergoing antiviral treatment CHB cohort, most HCC prediction models performed well even using on-treatment values during first 2 years, particularly REAL-B, AASL-HCC, CAMD, and mPAGE-B model.
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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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Poynard T, Lacombe JM, Deckmyn O, Peta V, Akhavan S, Zoulim F, de Ledinghen V, Samuel D, Mathurin P, Ratziu V, Thabut D, Housset C, Fontaine H, Pol S, Carrat F. External Validation of LCR1-LCR2, a Multivariable Hepatocellular Carcinoma Risk Calculator, in a Multiethnic Cohort of Patients With Chronic Hepatitis B. GASTRO HEP ADVANCES 2022; 1:604-617. [PMID: 39132068 PMCID: PMC11308549 DOI: 10.1016/j.gastha.2022.02.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Accepted: 02/09/2022] [Indexed: 08/13/2024]
Abstract
Background and Aims The liver cancer risk test (LCR1-LCR2) is a multianalyte blood test combining proteins involved in liver cell repair (apolipoprotein A1, haptoglobin), hepatocellular carcinoma (HCC) risk factors (gender, age, gamma glutamyl transpeptidase), a marker of fibrosis (alpha2-macroglobulin), and alpha-fetoprotein, a specific marker of HCC. The aim was to externally validate LCR1-LCR2 in hepatitis B. Methods Preincluded patients were from the Hepather cohort, a multicenter, multiethnic prospective study in 6071 patients. The coprimary study outcome was the negative predictive value of LCR1-LCR2 at 5 years for the occurrence of HCC and survival without HCC according to the predetermined LCR1-LCR2 cutoffs, adjusted for risk covariables and for chronic hepatitis B treatment and quantified using time-dependent Cox proportional hazards models. A post hoc analysis compared the number of patients needed to screen one cancer by LCR1-LCR2 and PAGE-B. Results A total of 3520 patients, 191 (5.4%) with cirrhosis, with at least 1 year of follow-up were included. A total of 76 HCCs occurred over a median (interquartile range) of 6.0 years (4.8-7.3) of follow-up. Among the 3367 patients with low-risk LCR1-LCR2, the 5-year negative predictive value was 99.3% (95% confidence interval = 99.0-99.6), with a significant Cox hazard ratio (6.4, 3.1-13.0; P < .001) obtained after adjustment for exposure to antivirals, age, gender, geographical origin, HBe-Ag status, alcohol consumption, and type-2 diabetes. LCR1-LCR2 outperformed PAGE-B for number of patients needed to screen mean (95% CI), 8.5 (3.2-8.1) vs 26.3 (17.5-38.5; P < .0001), respectively. Conclusion The performance of LCR1-LCR2 to identify patients with chronic hepatitis B at very low risk of HCC at 5 years was externally validated. ClinicalTrials.gov: NCT01953458.
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Affiliation(s)
- Thierry Poynard
- Department of Hepato-Gastroenterology, Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié-Salpêtrière Hospital, Paris, France
- INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Sorbonne Université, Paris, France
| | - Jean Marc Lacombe
- INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique, Sorbonne Université, Paris, France
| | | | - Valentina Peta
- INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Sorbonne Université, Paris, France
- Research Unit, BioPredictive, Paris, France
| | - Sepideh Akhavan
- Department of Hepato-Gastroenterology, Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié-Salpêtrière Hospital, Paris, France
| | - Fabien Zoulim
- Hepatology Unit Hôpital Haut-Lévêque, Pessac, and INSERM U1053, Université Bordeaux Segalen, Bordeaux, France
| | - Victor de Ledinghen
- Department of Hepatology, Hospices civils de Lyon, Hôpital Croix Rousse, INSERM U1052, Université de Lyon, Lyon, France
| | - Didier Samuel
- Hepatology Department, AP-HP, Hospital Paul Brousse, UMR-S1193, Villejuif, Université Paris-Saclay, and Hepatinov, Villejuif, France
| | | | - Vlad Ratziu
- Department of Hepato-Gastroenterology, Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié-Salpêtrière Hospital, Paris, France
- INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Sorbonne Université, Paris, France
| | - Dominique Thabut
- Department of Hepato-Gastroenterology, Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié-Salpêtrière Hospital, Paris, France
- INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Sorbonne Université, Paris, France
| | - Chantal Housset
- INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Sorbonne Université, Paris, France
| | - Hélène Fontaine
- Assistance Publique-Hôpitaux de Paris (AP-HP), Department of Hepato-Gastroenterology, AP-HP, Hôpital Cochin, Hepatology Department, Paris, France
| | - Stanislas Pol
- Assistance Publique-Hôpitaux de Paris (AP-HP), Department of Hepato-Gastroenterology, AP-HP, Hôpital Cochin, Hepatology Department, Paris, France
| | - Fabrice Carrat
- INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique, Sorbonne Université, Paris, France
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Oh H, Lee HY, Kim J, Kim YJ. Systematic Review with Meta-Analysis: Comparison of the Risk of Hepatocellular Carcinoma in Antiviral-Naive Chronic Hepatitis B Patients Treated with Entecavir versus Tenofovir: The Devil in the Detail. Cancers (Basel) 2022; 14:2617. [PMID: 35681596 PMCID: PMC9179302 DOI: 10.3390/cancers14112617] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 05/18/2022] [Accepted: 05/21/2022] [Indexed: 01/27/2023] Open
Abstract
Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are the preferred anti-viral agents used as first-line treatments for chronic hepatitis B (CHB). However, the efficacy of these agents in reducing the incidence of hepatocellular carcinoma (HCC) remains unclear. We conducted this meta-analysis to assess the efficacy of anti-viral agent on preventing HCC in CHB. Two investigators independently searched all relevant studies that examined the efficacy of anti-viral agent for preventing HCC using MEDLINE, Embase, and Cochrane Library databases through August 2021. The extracted data were analysed using a random-effects meta-analysis model based on the inverse-variance method (DerSimonian-Laird) and expressed as hazard ratio (HR) and 95% confidence interval (95% CI). We included 19 retrospective studies in the analysis. Although there was substantial heterogeneity between the studies, the overall pooled HR indicated that TDF significantly lowered the risk of HCC (HR: 0.72, 95% CI: 0.58-0.90, I2 = 66.29%). However, the pooled analysis of propensity score (PS)-matched subpopulations showed no significant differences (HR, 0.83; 95% CI, 0.65-1.06; I2 = 52.30%) between TDF and ETV. In a subgroup analysis, an interval of over three years in the start point of patient enrolment and excluding alcoholic liver disease patients significantly lowered the HCC risk associated with TDF. In conclusion, TDF may be more effective than ETV at reducing HCC incidence in treatment-naive CHB patients, but this effect was not consistent in the PS-matched subpopulation that reduced heterogeneity. As a result of subgroup analysis, the conflicting findings of previous studies may result from heterogeneous inclusion criteria. Further studies with standardised protocols are needed to reduce the residual heterogeneity.
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Affiliation(s)
- Hyunwoo Oh
- Department of Internal Medicine, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Uijeongbu 11759, Korea; (H.O.); (H.Y.L.)
| | - Hyo Young Lee
- Department of Internal Medicine, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Uijeongbu 11759, Korea; (H.O.); (H.Y.L.)
| | - Jihye Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea;
| | - Yoon Jun Kim
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea
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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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Costa APDM, da Silva MACN, Castro RS, Sampaio ALDO, Alencar Júnior AM, da Silva MC, Ferreira ADSP. PAGE-B and REACH-B Predicts the Risk of Developing Hepatocellular Carcinoma in Chronic Hepatitis B Patients from Northeast, Brazil. Viruses 2022; 14:v14040732. [PMID: 35458462 PMCID: PMC9033073 DOI: 10.3390/v14040732] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 03/25/2022] [Accepted: 03/29/2022] [Indexed: 12/14/2022] Open
Abstract
This study aims to evaluate the accuracy of the PAGE-B and REACH-B scores in predicting the risk of developing HCC in patients with chronic hepatitis B regularly followed up at a reference service in the State of Maranhão. A historical, longitudinal, retrospective cohort study, carried out from the review of medical records of patients with chronic Hepatitis B. PAGE-B and REACH-B scores were calculated and the accuracy of the scores in predicting the risk of HCC in the studied population was evaluated. A total of 978 patients were included, with a median age of around 47 years, most of them female and not cirrhotic. HCC was identified in 34 patients. Thrombocytopenia, high viral load, male gender and age were associated with the occurrence of HCC. The ROC curve for the PAGE-B score showed a value of 0.78 and for the REACH-B score of 0.79. The cutoff point for PAGE-B was 11 points for greater sensitivity and for REACH-B 7.5 points considering greater sensitivity and 9.5 points considering greater specificity. PAGE-B and REACH-B scores were able to predict the risk of developing HCC in the studied population. The use of risk stratification scores is useful to reduce costs associated with HCC screening.
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Affiliation(s)
- Alessandra Porto de Macedo Costa
- Center for Liver Studies, University Hospital of the Federal University of Maranhão, Saint Louis CEP 65020-070, MA, Brazil; (A.P.d.M.C.); (R.S.C.); (A.L.d.O.S.); (A.M.A.J.)
| | | | - Rogério Soares Castro
- Center for Liver Studies, University Hospital of the Federal University of Maranhão, Saint Louis CEP 65020-070, MA, Brazil; (A.P.d.M.C.); (R.S.C.); (A.L.d.O.S.); (A.M.A.J.)
| | - Ana Leatrice de Oliveira Sampaio
- Center for Liver Studies, University Hospital of the Federal University of Maranhão, Saint Louis CEP 65020-070, MA, Brazil; (A.P.d.M.C.); (R.S.C.); (A.L.d.O.S.); (A.M.A.J.)
| | - Antônio Machado Alencar Júnior
- Center for Liver Studies, University Hospital of the Federal University of Maranhão, Saint Louis CEP 65020-070, MA, Brazil; (A.P.d.M.C.); (R.S.C.); (A.L.d.O.S.); (A.M.A.J.)
| | - Márcia Costa da Silva
- Epidemiological Surveillance Service, State Health Department, Saint Louis CEP 65076-820, MA, Brazil;
| | - Adalgisa de Souza Paiva Ferreira
- Center for Liver Studies, University Hospital of the Federal University of Maranhão, Saint Louis CEP 65020-070, MA, Brazil; (A.P.d.M.C.); (R.S.C.); (A.L.d.O.S.); (A.M.A.J.)
- Correspondence: (M.A.C.N.d.S.); (A.d.S.P.F.)
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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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Comparative performance of risk prediction models for hepatitis B-related hepatocellular carcinoma in the United States. J Hepatol 2022; 76:294-301. [PMID: 34563579 PMCID: PMC8786210 DOI: 10.1016/j.jhep.2021.09.009] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 08/24/2021] [Accepted: 09/03/2021] [Indexed: 01/29/2023]
Abstract
BACKGROUND & AIMS Guidelines recommend hepatocellular carcinoma (HCC) surveillance in patients with chronic HBV infection. Several HCC risk prediction models are available to guide surveillance decisions, but their comparative performance remains unclear. METHODS Using a retrospective cohort of patients with HBV treated with nucleos(t)ide analogues at 130 Veterans Administration facilities between 9/1/2008 and 12/31/2018, we calculated risk scores from 10 HCC risk prediction models (REACH-B, PAGE-B, m-PAGE-B, CU-HCC, HCC-RESCUE, CAMD, APA-B, REAL-B, AASL-HCC, RWS-HCC). We estimated the models' discrimination and calibration. We calculated HCC incidence in risk categories defined by the reported cut-offs for all models. RESULTS Of 3,101 patients with HBV (32.2% with cirrhosis), 47.0% were treated with entecavir, 40.6% tenofovir, and 12.4% received both. During a median follow-up of 4.5 years, 113 patients developed HCC at an incidence of 0.75/100 person-years. AUC values for 3-year HCC risk were the highest for RWS-HCC, APA-B, REAL-B, and AASL-HCC (all >0.80). Of these, 3 (APA-B, RWS-HCC, REAL-B) incorporated alpha-fetoprotein. AUC values for the other models ranged from 0.73 for PAGE-B to 0.79 for CAMD and HCC-RESCUE. Of the 7 models with AUC >0.75, only APA-B was poorly calibrated. In total, 10-20% of the cohort was deemed low-risk based on the published cut-offs. None of the patients in the low-risk groups defined by PAGE-B, m-PAGE-B, AASL-HCC, and REAL-B developed HCC during the study timeframe. CONCLUSION In this national cohort of US-based patients with HBV on antiviral treatment, most models performed well in predicting HCC risk. A low-risk group, in which no cases of HCC occurred within a 3-year timeframe, was identified by several models (PAGE-B, m-PAGE-B, CAMD, AASL-HCC, REAL-B). Further studies are warranted to examine whether these patients could be excluded from HCC surveillance. LAY SUMMARY Risk prediction models for hepatocellular carcinoma (HCC) in patients infected with hepatitis B virus (HBV) could guide HCC surveillance decisions. In this large cohort of US-based patients receiving treatment for HBV, most published models discriminated between those who did or did not develop HCC, although the RWS-HCC, REAL-B, and AASL-HCC performed the best. If confirmed in future studies, these models could help identify a low-risk subset of patients on antiviral treatment who could be excluded from HCC surveillance.
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Wang S, Liu B, Fan X, Gao Y, Hong M, Xu Y. Predicting the risk of hepatocellular carcinoma in chronic hepatitis B patients receiving antiviral therapy: Validating the CAMD and AASL scores in China. Saudi J Gastroenterol 2022; 28:362-368. [PMID: 35170433 PMCID: PMC9752533 DOI: 10.4103/sjg.sjg_527_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
BACKGROUND We aimed to validate the predictive value of the cirrhosis, age, male sex, and diabetes (CAMD) score and age, albumin, sex, and liver cirrhosis (AASL) score for chronic hepatitis B (CHB) patients, treated with nucleos(t)ide analogues (NUCs) in Northeast China. METHODS From January 2009 to June 2020, 945 patients diagnosed with CHB who received NUC therapy at China-Japan Union Hospital of Jilin University were included. Comprehensive medical records were retrospectively analyzed, and the predictive values of the CAMD score and AASL score for hepatocellular carcinoma (HCC) were evaluated. RESULTS A total of 58 patients (5.94%) were diagnosed with HCC. Multivariate analysis revealed that age [odds ratio (OR) = 1.041, 95% confidence interval (CI) 1.009-1.073, P < 0.011] and cirrhosis (OR = 3.297, 95% CI 1.383-7.861, P < 0.007) were independent predictors of HCC. Either the CAMD or AASL score was significantly higher in the HCC group compared to the non-HCC group. The area under the receiver operating characteristic (ROC) curve (AUC) of CAMD and AASL was 0.721 (95% CI 0.663-0.780) and 0.718 (95% CI 0.662-0.774), respectively. Risk stratification using either CAMD or AASL revealed significant differences in the one-, three-, and five-year cumulative incidence rates of HCC between the low-, intermediate-, and high-risk groups (all P < 0.001, log-rank test). CONCLUSIONS Both CAMD and AASL scores have predictive value for HCC risk of CHB patients in Northeast China. In future, the optimal monitoring frequency and methods should be personalized.
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Affiliation(s)
- Shuai Wang
- Department of Gastroenterology, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Bingwei Liu
- Department of Critical Care Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xuemei Fan
- Department of Gastroenterology, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Yang Gao
- Department of Gastroenterology, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Mingqi Hong
- Department of Gastroenterology, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Yan Xu
- Department of Gastroenterology, China-Japan Union Hospital of Jilin University, Changchun, China,Address for correspondence: Dr. Yan Xu, Department of Gastroenterology, China-Japan Union Hospital of Jilin University, Changchun, Jilin - 130 033, China. E-mail:
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Wu S, Zeng N, Sun F, Zhou J, Wu X, Sun Y, Wang B, Zhan S, Kong Y, Jia J, You H, Yang HI. Hepatocellular Carcinoma Prediction Models in Chronic Hepatitis B: A Systematic Review of 14 Models and External Validation. Clin Gastroenterol Hepatol 2021; 19:2499-2513. [PMID: 33667678 DOI: 10.1016/j.cgh.2021.02.040] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Revised: 02/25/2021] [Accepted: 02/26/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The aim of our study was to characterize the performance of hepatocellular carcinoma (HCC) prediction models in chronic hepatitis B (CHB) patients through meta-analysis followed by external validation. METHODS We performed a systematic review and meta-analysis of current literature, followed by external validation in independent multi-center cohort with 986 patients with CHB undergoing entecavir treatment (median follow-up: 4.7 years). Model performance to predict HCC within 3, 5, 7, and 10 years was assessed using area under receiver operating characteristic curve (AUROC) and calibration index. Subgroup analysis were conducted by treatment status, cirrhotic, race and baseline alanine aminotransferase. RESULTS We identified 14 models with 123,885 patients (5,452 HCC cases), with REACH-B, CU-HCC, GAG-HCC, PAGE-B and mPAGE-B models being broadly externally validated. Discrimination was generally acceptable for all models, with pooled AUC ranging from 0.70 (95% CI, 0.63-0.76 for REACH-B) to 0.83 (95% CI, 0.78-0.87 for REAL-B) for 3-year, 0.68 (95% CI, 0.64-0.73 for REACH-B) to 0.81 (95% CI, 0.77-0.85 for REAL-B) for 5-year and 0.70 (95% CI, 0.58-0.80 for PAGE-B) to 0.81 (95% CI, 0.78-0.84 for REAL-B and 0.77-0.86 for AASL-HCC) for 10-year prediction. However, calibration performance was poorly reported in most studies. In external validation cohort, REAL-B showed highest discrimination with 0.76 (95% CI, 0.69-0.83) and 0.75 (95% CI, 0.70-0.81) for 3 and 5-year prediction. The REAL-B model was also well calibrated in the external validation cohort (3-year Brier score 0.066). Results were consistent in subgroup analyses. CONCLUSIONS In a systematic review of available HCC models, the REAL-B model exhibited best discrimination and calibration.
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Affiliation(s)
- Shanshan Wu
- National Clinical Research Center of Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, Mainland China
| | - Na Zeng
- National Clinical Research Center of Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, Mainland China
| | - Feng Sun
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, Mainland China
| | - Jialing Zhou
- Liver Research Center, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing Friendship Hospital, Capital Medical University, Beijing, Mainland China
| | - Xiaoning Wu
- Liver Research Center, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing Friendship Hospital, Capital Medical University, Beijing, Mainland China
| | - Yameng Sun
- Liver Research Center, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing Friendship Hospital, Capital Medical University, Beijing, Mainland China
| | - Bingqiong Wang
- Liver Research Center, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing Friendship Hospital, Capital Medical University, Beijing, Mainland China
| | - Siyan Zhan
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, Mainland China
| | - Yuanyuan Kong
- National Clinical Research Center of Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, Mainland China
| | - Jidong Jia
- National Clinical Research Center of Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, Mainland China; Liver Research Center, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing Friendship Hospital, Capital Medical University, Beijing, Mainland China
| | - Hong You
- National Clinical Research Center of Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, Mainland China; Liver Research Center, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing Friendship Hospital, Capital Medical University, Beijing, Mainland China.
| | - 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.
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Yu JH, Cho SG, Jin YJ, Lee JW. The best predictive model for hepatocellular carcinoma in patients with chronic hepatitis B infection. Clin Mol Hepatol 2021; 28:351-361. [PMID: 34823308 PMCID: PMC9293610 DOI: 10.3350/cmh.2021.0281] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Accepted: 11/25/2021] [Indexed: 11/06/2022] Open
Abstract
Chronic hepatitis B (CHB) seriously threatens human health. About 820,000 deaths annually are due to related complications such as hepatitis B and hepatocellular carcinoma (HCC). Recently, the use of oral antiviral agents has significantly improved the prognosis of patients with CHB infection and reduced the risk of HCC. However, hepatitis B virus still remains a major factor in the development of HCC, raising many concerns. Therefore, numerous studies have been conducted to assess the risk of HCC in patients with CHB infection and many models have been proposed to predict the risk of developing HCC. However, as each study has different models for predicting HCC development that can be applied depending on the use of antiviral agents or the type of antiviral agents, it is necessary to properly understand characteristics of each model when using it for the evaluation of HCC in patients with CHB infection. In addition, because different variables such as host factor, viral activity, and cirrhosis are used to evaluate the risk of HCC development, it is necessary to assess the risk by carefully verifying which variables are used. Recently, studies have also evaluated the risk of HCC using risk prediction models through transient elastography and artificial intelligence (AI) system. These HCC risk predication models are also noteworthy. In this review, we aimed to compare HCC risk prediction models in patients with CHB infection reported to date to confirm variables used and specificity between each model to determine an appropriate HCC risk prediction method.
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Affiliation(s)
- Jung Hwan Yu
- Department of Internal Medicine, Inha University Hospital and School of Medicine, Incheon, South Korea
| | - Soon Gu Cho
- Department of Radiology, Inha University Hospital and School of Medicine, Incheon, South Korea
| | - Young-Joo Jin
- Department of Internal Medicine, Inha University Hospital and School of Medicine, Incheon, South Korea
| | - Jin-Woo Lee
- Department of Internal Medicine, Inha University Hospital and School of Medicine, Incheon, South Korea
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Cirrhosis, Age, and Liver Stiffness-Based Models Predict Hepatocellular Carcinoma in Asian Patients with Chronic Hepatitis B. Cancers (Basel) 2021; 13:cancers13225609. [PMID: 34830764 PMCID: PMC8615754 DOI: 10.3390/cancers13225609] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Revised: 11/01/2021] [Accepted: 11/05/2021] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVES Predicting hepatocellular carcinoma (HCC) in patients with chronic hepatitis B who received long-term therapy with potent nucleos(t)ide analogs is of utmost importance to refine the strategy for HCC surveillance. METHODS We conducted a multicenter retrospective cohort study to validate the CAGE-B and SAGE-B scores, HCC prediction models developed for Caucasian patients receiving entecavir (ETV) or tenofovir (TFV) for >5 years. Consecutive patients who started ETV or TFV at two hospitals in Korea from January 2009 to December 2015 were identified. The prediction scores were calculated, and model performance was assessed using receiver operating characteristics (ROC) curves. RESULTS Among 1557 patients included, 57 (3.7%) patients had HCC during a median follow-up of 93 (95% confidence interval, 73-119) months. In the entire cohort, CAGE-B predicted HCC with an area under the ROC curve of 0.78 (95% CI, 0.72-0.84). Models that have "liver cirrhosis" in the calculation, such as AASL (0.79 (0.72-0.85)), CU-HCC (0.77 (0.72-0.82)), and GAG-HCC (0.79 (0.74-0.85)), showed accuracy similar to that of CAGE-B (p > 0.05); however, models without "liver cirrhosis", including SAGE-B (0.71 (0.65-0.78)), showed a lower predictive ability than CAGE-B. CAGE-B performed well in subgroups of patients treated without treatment modification (0.81 (0.73-0.88)) and of male sex (0.79 (0.71-0.86)). CONCLUSIONS This study validated the clinical usefulness of the CAGE-B score in a large number of Asian patients treated with long-term ETV or TFV. The results could provide the basis for the reappraisal of HCC surveillance strategies and encourage future prospective validation studies with liver stiffness measurements.
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Demirtas CO, Brunetto MR. Surveillance for hepatocellular carcinoma in chronic viral hepatitis: Is it time to personalize it? World J Gastroenterol 2021; 27:5536-5554. [PMID: 34588750 PMCID: PMC8433616 DOI: 10.3748/wjg.v27.i33.5536] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Revised: 04/28/2021] [Accepted: 08/02/2021] [Indexed: 02/06/2023] Open
Abstract
Surveillance with abdominal ultrasound with or without alpha-fetoprotein is recommended by clinical practice guidelines for patients who are considered to be at risk of developing hepatocellular carcinoma (HCC), including those with cirrhosis, advanced fibrosis and special subgroups of chronic hepatitis B (CHB). Application of the standard surveillance strategy to all patients with chronic liver disease (CLD) with or without cirrhosis imposes major sustainability and economic burdens on healthcare systems. Thus, a number of HCC risk scores were constructed, mainly from Asian cohorts, to stratify the HCC prediction in patients with CHB. Similarly, even if less than for CHB, a few scoring systems were developed for chronic hepatitis C patients or cirrhotic patients with CLD of different etiologies. Recently, a few newsworthy HCC-risk algorithms were developed for patients with cirrhosis using the combination of serologic HCC markers and clinical parameters. Overall, the HCC risk stratification appears at hand by several validated multiple score systems, but their optimal performance is obtained only in populations who show highly homogenous clinic-pathologic, epidemiologic, etiologic and therapeutic characteristics and this limitation poses a major drawback to their sustainable use in clinical practice. A better understanding of the dynamic process driving the progression from CLD to HCC derived from studies based on molecular approaches and genetics, epigenetics and liquid biopsy will enable the identification of new biomarkers to define the individual risk of HCC in the near future, with the possibility to achieve a real and cost/effective personalization of surveillance.
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Affiliation(s)
- Coskun Ozer Demirtas
- Department of Gastroenterology and Hepatology, Marmara University, School of Medicine, Istanbul 34854, Turkey
| | - Maurizia Rossana Brunetto
- Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa 56125, Italy
- Hepatology Unit, University Hospital of Pisa, Pisa 56125, Italy
- Biostructure and Bio-imaging Institute, National Research Council of Italy, Naples 56125, Italy
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Ren P, Li H, Huang Y, Jiang J, Guo S, Cao Z, Zhang C, Zhou T, Gan Q, Zhao S, Chen L, Guo Q, Cai W, Wang H, Hu P, Xie Q. A simple-to-use tool for predicting response to peginterferon in HBV DNA suppressed chronic hepatitis B patients in China. Antiviral Res 2021; 194:105163. [PMID: 34389410 DOI: 10.1016/j.antiviral.2021.105163] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 06/07/2021] [Accepted: 08/09/2021] [Indexed: 11/26/2022]
Abstract
BACKGROUND Rational administration of peginterferon can remarkably reduce serum HBsAg level and improve the rate of HBsAg loss. Considering the high cost and adverse drug reaction of peginterferon, we aimed to develop a simple-to-use scoring system at early stage of treatment to predict low HBsAg level or HBsAg clearance at the end of treatment in virological suppression chronic hepatitis B (CHB) patients. METHODS Non-cirrhotic CHB patients with NA (nucleoside/nucleotide analogues)-induced virological suppression initiated either by add-on or switch-to peginterferon for ≥ 48 weeks were enrolled from January 2012 to June 2017 in these two tertiary centers. The retrospective experiment identified 320 suitable patients, including 192 in training and 128 in validation cohorts. RESULTS Using logistic regression, a simple-to-use scoring system integrating baseline HBsAg level <1000 IU/mL, HBsAg decline >0.5 log at week 12 and ALT flare at week 12 was developed in the training cohort and good for predicting HBsAg <100 IU/mL, HBsAg <10 IU/mL and HBsAg loss at the end of 48-week treatment. The area under receiver operating characteristics curve was 0.84, 0.86 or 0.78 in the training cohort and 0.88, 0.79 or 0.81 in the validation cohort, respectively. CONCLUSIONS Our simple-to-use scoring system may guide for clinicians to decide whether to continue peginterferon in CHB patients to achieve low HBsAg levels or HBsAg clearance at the end of treatment, which might lead more cost-effective decision and get more patients to reach functional cures in Chinese population.
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Affiliation(s)
- Peipei Ren
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Hu Li
- Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China
| | - Yan Huang
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Jiayuan Jiang
- Clinical Research Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Simin Guo
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Zhujun Cao
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Chenxi Zhang
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Tianhui Zhou
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Qinyi Gan
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Shuang Zhao
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Lichang Chen
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Qing Guo
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Wei Cai
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Hui Wang
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Peng Hu
- Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
| | - Qing Xie
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
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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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Cheng R, Xu J, Tan N, Luo H, Pan J, Xu X. Predictive Nomograms for Clinical Outcomes in Hepatitis B-Related Cirrhosis Patients Receiving Antiviral Therapy. Infect Drug Resist 2021; 14:2707-2719. [PMID: 34290509 PMCID: PMC8289317 DOI: 10.2147/idr.s316026] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Accepted: 06/29/2021] [Indexed: 11/30/2022] Open
Abstract
Objective Many scores have been constructed to predict liver-related events in chronic hepatitis B, while most of them are based on baseline clinical parameters. The objective of this study was to develop nomograms based on on-treatment improvement in established scores to predict clinical outcomes in patients with hepatitis B virus (HBV)-related cirrhosis who are receiving antiviral therapy. Methods The Cox proportional hazards regression model was used. Nomograms were constructed for the prediction of liver-related events, hepatocellular carcinoma (HCC), and liver-related mortality risk during long-term antiviral therapy. Results A total of 277 treatment-naive patients with HBV-associated cirrhosis were enrolled from January 2010 to December 2013. After a median follow-up of 63.3 months, 95 patients developed liver-related events, including 59 patients with liver-related death. Multivariate Cox analysis showed that the albumin-bilirubin score at year 1 was an independent predictor of liver-related events, liver-related mortality, and HCC. Age, decompensation, and delayed virological remission were independent factors for liver-related mortality. Age was also a risk factor for liver-related events. The concordance index values of event-nomogram, mortality-nomogram, and HCC-nomogram were 0.742 (95% confidence interval [CI], 0.691~0.793), 0.799 (95% CI, 0.748~0.850), and 0.613 (95% CI, 0.540~0.686), respectively. The calibration plots showed an agreement between the predicted and observed incidences, which indicates good calibration of the model of event-nomogram and mortality-nomogram. Conclusion The nomograms achieved an optimal preoperative prediction of liver-related events, mortality, and HCC development in patients with HBV-related cirrhosis receiving antiviral therapy. These findings may help to identify high-risk patients for further optimal surveillance and intervention strategies.
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Affiliation(s)
- Ran Cheng
- Department of Infectious Diseases, Peking University First Hospital, Beijing, People's Republic of China
| | - Jinghang Xu
- Department of Infectious Diseases, Peking University First Hospital, Beijing, People's Republic of China
| | - Ning Tan
- Department of Infectious Diseases, Peking University First Hospital, Beijing, People's Republic of China
| | - Hao Luo
- Department of Infectious Diseases, Peking University First Hospital, Beijing, People's Republic of China
| | - Jiali Pan
- Department of Infectious Diseases, Peking University First Hospital, Beijing, People's Republic of China
| | - Xiaoyuan Xu
- Department of Infectious Diseases, Peking University First Hospital, Beijing, People's Republic of China
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40
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Sachar Y, Brahmania M, Dhanasekaran R, Congly SE. Screening for Hepatocellular Carcinoma in Patients with Hepatitis B. Viruses 2021; 13:1318. [PMID: 34372524 PMCID: PMC8310362 DOI: 10.3390/v13071318] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 07/05/2021] [Accepted: 07/05/2021] [Indexed: 12/18/2022] Open
Abstract
Chronic hepatitis B (CHB) infection is a significant risk factor for developing hepatocellular carcinoma (HCC). As HCC is associated with significant morbidity and mortality, screening patients with CHB at a high risk for HCC is recommended in an attempt to improve these outcomes. However, the screening recommendations on who to screen and how often are not uniform. Identifying patients at the highest risk of HCC would allow for the best use of health resources. In this review, we evaluate the literature on screening patients with CHB for HCC, strategies for optimizing adherence to screening, and potential risk stratification tools to identify patients with CHB at a high risk of developing HCC.
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Affiliation(s)
- Yashasavi Sachar
- London Health Sciences Center, Department of Medicine, Division of Gastroenterology, Western University, London, ON N6A 5A5, Canada; (Y.S.); (M.B.)
| | - Mayur Brahmania
- London Health Sciences Center, Department of Medicine, Division of Gastroenterology, Western University, London, ON N6A 5A5, Canada; (Y.S.); (M.B.)
- Centre for Quality, Innovation and Safety, Schulich School of Medicine & Dentistry, Western University, London, ON N6A 5W9, Canada
| | - Renumathy Dhanasekaran
- Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University, Stanford, CA 94305, USA;
| | - Stephen E. Congly
- Department of Medicine, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4Z6, Canada
- O’Brien Institute of Public Health, University of Calgary, Calgary, AB T2N 4Z6, Canada
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Kamalapirat T, Yingcharoen K, Ungtrakul T, Soonklang K, Dechma J, Chunnuan P, Kusuman P, Pothijaroen C, Tawpa J, Cheirsilpa K, Auewarakul C. Assessing risk scores for predicting hepatocellular carcinoma in Thai patients with chronic hepatitis B. J Viral Hepat 2021; 28:1034-1041. [PMID: 33880807 DOI: 10.1111/jvh.13517] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2020] [Revised: 03/16/2021] [Accepted: 04/04/2021] [Indexed: 12/12/2022]
Abstract
Chronic hepatitis B (CHB) infection-associated hepatocellular carcinoma (HCC) is a major health problem in Asian countries. Several HCC risk prediction models have been developed using either treated or untreated CHB patients. However, there is limited validation of these risk scores in a treated and untreated mixed CHB patient cohort. This study analysed and validated HCC risk scores among 2208 CHB patients who enrolled in the HCC surveillance programme in Thailand during July 2010. The baseline clinical and radiologic data of these CHB patients were applied to calculate various HCC risk scores. There were 20 patients (0.9%) with HCC development at the 5.9-year follow-up. The areas under the receiver operating characteristic curves (AUROCs) predicting HCC risk at 5 years were 0.80 (0.68-0.91), 0.73 (0.60-0.85), 0.79 (0.67-0.91), 0.70 (0.58-0.82), 0.72 (0.59-0.85), 0.76 (0.63-0.87) and 0.77 (0.64-0.89) for the GAG-HCC, CU-HCC, REACH-B, PAGE-B, mPAGE-B, CAMD and AASL scores, respectively. The overall HCC risk scores were accurate and comparable. However, the subgroup analysis revealed better HCC-risk-predictive performance in the treated patients, while performance was less helpful in those not fulfilling criteria for antiviral therapy. Clinicians should be aware of these data when using the HCC risk score in untreated CHB patients.
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Affiliation(s)
- Thanachote Kamalapirat
- Faculty of Medicine and Public Health, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Kesinee Yingcharoen
- Chulabhorn Hospital, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Teerapat Ungtrakul
- Faculty of Medicine and Public Health, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Kamonwan Soonklang
- Data Management Unit, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Jiraporn Dechma
- Chulabhorn Hospital, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Pitchayachuda Chunnuan
- Chulabhorn Hospital, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Pattama Kusuman
- Chulabhorn Hospital, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Charinthip Pothijaroen
- Chulabhorn Hospital, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Jantarika Tawpa
- Chulabhorn Hospital, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Kunsuda Cheirsilpa
- Chulabhorn Hospital, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Chirayu Auewarakul
- Faculty of Medicine and Public Health, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand
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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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Papatheodoridis GV, Dalekos GN, Idilman R, Sypsa V, Van Boemmel F, Buti M, Calleja JL, Goulis J, Manolakopoulos S, Loglio A, Papatheodoridi M, Gatselis N, Veelken R, Lopez-Gomez M, Hansen BE, Savvidou S, Kourikou A, Vlachogiannakos J, Galanis K, Yurdaydin C, Esteban R, Janssen HL, Berg T, Lampertico P. Predictive performance of newer Asian hepatocellular carcinoma risk scores in treated Caucasians with chronic hepatitis B. JHEP Rep 2021; 3:100290. [PMID: 34041470 PMCID: PMC8144729 DOI: 10.1016/j.jhepr.2021.100290] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 03/23/2021] [Accepted: 03/25/2021] [Indexed: 12/22/2022] Open
Abstract
Background & Aims Recently, several risk scores for prediction of hepatocellular carcinoma (HCC) were developed in cohorts of treated Asian patients with chronic hepatitis B (CHB), but they have not been assessed in non-Asian patients. We evaluated the predictability and comparative utility of our PAGE-B and recent Asian HCC risk scores in nucleos(t)ide analogue (NA)-treated adult Caucasian patients with CHB, with or without well-documented compensated cirrhosis but not previous diagnosis of HCC. Methods We included 1,951 patients treated with entecavir/tenofovir and followed up for a median of 7.6 years. The c-statistic was used to estimate the predictability of PAGE-B, HCC-Rescue, CAMD, mPAGE-B, and AASL score for HCC development within 5 or 10 years. The low- and high-risk group cut-offs were used for estimation of negative (NPV) and positive predictive values (PPV), respectively. Results HCC developed in 103/1,951 (5.3%) patients during the first 5 years and in another 39/1,428 (2.7%) patients between years 5 and 10. The 3-, 5-, and 10-year cumulative HCC rates were 3.3%, 5.9%, and 9.6%, respectively. All scores offered good 5- and 10-year HCC prediction (c-statistic: 0.78–0.82). NPVs were always >99% (99.3–100%), whereas PPV ranged between 13% and 24%. Conclusions In NA-treated Caucasian patients with CHB including compensated cirrhosis, HCC risk scores developed in NA-treated Asian patients offer good 5- and 10-year HCC predictability, similar to that of PAGE-B. PAGE-B and mPAGE-B scores are simpler in clinical practice, as they do not require an accurate diagnosis of cirrhosis, but the addition of albumin in mPAGE-B score does not seem to offer an advantage in patients with well compensated liver disease. Lay summary Several risk scores for prediction of hepatocellular carcinoma (HCC) were recently developed in cohorts of treated Asian patients with chronic hepatitis B (CHB). In Caucasian patients with CHB treated with oral antivirals, newer Asian HCC risk scores offer good 5- and 10-year HCC predictability, similar to that of PAGE-B. For clinical practice, PAGE-B and mPAGE-B scores are simpler, as they do not require an accurate diagnosis of cirrhosis.
In treated Caucasian patients with chronic hepatitis B, newer Asian hepatocellular carcinoma risk scores offer good 5- and 10-year predictability, similar to that of PAGE-B. PAGE-B and mPAGE-B scores are simpler in clinical practice, as they do not require an accurate diagnosis of cirrhosis. The addition of albumin in mPAGE-B does not seem to offer an advantage in patients with well-compensated liver disease.
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Key Words
- ALT, alanine aminotransferase
- AUROC, area under receiver operating characteristic
- CHB, chronic hepatitis B
- Cirrhosis
- ETV, entecavir
- Entecavir
- HCC, hepatocellular carcinoma
- HR, hazard ratio
- NA, nucleos(t)ide analogue
- NPV, negative predictive value
- PPV, positive predictive value
- Prediction
- TDF, tenofovir disoproxil fumarate
- Tenofovir
- ULN, upper limit of normal
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Affiliation(s)
- George V. Papatheodoridis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens “Laiko”, Athens, Greece
- Corresponding author. Address: Department of Gastroenterology, School of Medicine, National and Kapodistrian University of Athens, Laiko General Hospital of Athens, 17 Agiou Thoma Street, 11527 Athens, Greece. Tel: +30-2132061115, Fax: +30-2107462601
| | - George N. Dalekos
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece
| | - Ramazan Idilman
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Vana Sypsa
- Department of Hygiene, Epidemiology & Medical Statistics, Medical School of National and Kapodistrian University of Athens, Athens, Greece
| | - Florian Van Boemmel
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
| | - Maria Buti
- Hospital General Universitario Vall Hebron and Ciberehd, Barcelona, Spain
| | | | - John Goulis
- 4th Department of Internal Medicine, Αristotle University of Thessaloniki Medical School, Thessaloniki, Greece
| | - Spilios Manolakopoulos
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens “Laiko”, Athens, Greece
- 2nd Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens “Hippokratio”, Athens, Greece
| | - Alessandro Loglio
- Division of Gastroenterology and Hepatology, CRC “A. M. and A. Migliavacca” Center for Liver Disease, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Margarita Papatheodoridi
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens “Laiko”, Athens, Greece
| | - Nikolaos Gatselis
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece
| | - Rhea Veelken
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
| | | | - Bettina E. Hansen
- Department of Gastroenterology & Hepatology, Erasmus MC University Medical Center, Rotterdam, Netherlands
- Liver Clinic, Toronto Western & General Hospital, University Health Network, Toronto, ON, Canada
| | - Savvoula Savvidou
- 4th Department of Internal Medicine, Αristotle University of Thessaloniki Medical School, Thessaloniki, Greece
| | - Anastasia Kourikou
- 2nd Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens “Hippokratio”, Athens, Greece
| | - John Vlachogiannakos
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens “Laiko”, Athens, Greece
| | - Kostas Galanis
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece
| | - Cihan Yurdaydin
- Department of Gastroenterology & Hepatology, Koc University Medical School, Istanbul, Turkey
| | - Rafael Esteban
- Hospital General Universitario Vall Hebron and Ciberehd, Barcelona, Spain
| | - Harry L.A. Janssen
- Liver Clinic, Toronto Western & General Hospital, University Health Network, Toronto, ON, Canada
| | - Thomas Berg
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
| | - Pietro Lampertico
- Division of Gastroenterology and Hepatology, CRC “A. M. and A. Migliavacca” Center for Liver Disease, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
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44
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Stratification of Hepatocellular Carcinoma Risk Following HCV Eradication or HBV Control. J Clin Med 2021; 10:jcm10020353. [PMID: 33477752 PMCID: PMC7832303 DOI: 10.3390/jcm10020353] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 01/07/2021] [Accepted: 01/13/2021] [Indexed: 12/18/2022] Open
Abstract
Hepatocellular carcinoma (HCC) incidence has dramatically decreased in patients infected with HCV and HBV due to the widespread use of highly effective antiviral agents. Nevertheless, a substantial proportion of patients with advanced fibrosis or cirrhosis following HCV clearance of in case of HBV control whatever the stage of fibrosis remains at risk of liver cancer development. Cancer predictors in these virus-free patients include routine parameters estimating coexisting comorbidities, persisting liver inflammation or function impairment, and results of non-invasive tests which can be easily combined into HCC risk scoring systems. The latter enables stratification according to various liver cancer incidences and allocation of patients into low, intermediate or high HCC risk probability groups. All international guidelines endorse lifelong surveillance of these patients using semi-annual ultrasound, with known sensibility issues. Refining HCC prediction in this growing population ultimately will trigger personalized management using more effective surveillance tools such as contrast-enhanced imaging techniques or circulating biomarkers while taking into account cost-effectiveness parameters.
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Chang JW, Lee JS, Lee HW, Kim BK, Park JY, Kim DY, Ahn SH, Seo YS, Lee HA, Kim MN, Lee YR, Hwang SG, Rim KS, Um SH, Tak WY, Kweon YO, Park SY, Kim SU. Validation of risk prediction scores for hepatocellular carcinoma in patients with chronic hepatitis B treated with entecavir or tenofovir. J Viral Hepat 2021; 28:95-104. [PMID: 33029863 DOI: 10.1111/jvh.13411] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 08/11/2020] [Accepted: 08/23/2020] [Indexed: 12/15/2022]
Abstract
Several prediction scores for the early detection of hepatocellular carcinoma (HCC) are available. We validated the predictive accuracy of age, albumin, sex, liver cirrhosis (AASL), RESCUE-B, PAGE-B and modified PAGE-B (mPAGE-B) scores in chronic hepatitis B (CHB) patients treated with entecavir (ETV) or tenofovir disoproxil fumarate (TDF). Between 2007 and 2014, 3171 patients were recruited (1645, ETV; 1517, TDF). The predictive accuracy of each prediction score was assessed. The mean age of the study population (1977 men; 1194 women) was 48.8 years. Liver cirrhosis was present in 1040 (32.8%) patients. During follow-up (median, 58.2 months), 280 (8.8%) patients developed HCC; these patients were significantly older; more likely to be male; had significantly higher proportions of liver cirrhosis, hypertension and diabetes; and had significantly higher values for the four risk scores than those who did not develop HCC (all P < .05). Older age (hazard ratio [HR] = 1.048), male sex (HR = 2.142), liver cirrhosis (HR = 3.144) and prolonged prothrombin time (HR = 2.589) were independently associated with an increased risk of HCC (all P < .05), whereas a higher platelet count (HR = 0.996) was independently associated with a decreased risk of HCC (P < .05). The predictive accuracy of AASL score was the highest for 3- and 5-year HCC predictions (areas under the curve [AUCs] = 0.818 and 0.816, respectively), followed by RESCUE-B, PAGE-B and mPAGE-B scores (AUC = 0.780-0.815 and 0.769-0.814, respectively). In conclusion, four HCC prediction scores were assessed in Korean CHB patients treated with ETV or TDF. The AASL score showed the highest predictive accuracy.
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Affiliation(s)
- Jin Won Chang
- Department of Internal Medicine, Yonsei University College of Medicine, 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
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Hye Won Lee
- 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
| | - 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
| | - 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
| | - Yeon Seok Seo
- Department of Internal Medicine, Korea University College of Medicine, 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
| | - Yu Rim Lee
- Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea
| | - Seong Gyu Hwang
- Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - Kyu Sung Rim
- Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - Soon Ho Um
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Won Young Tak
- Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea
| | - Young Oh Kweon
- Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea
| | - Soo Young Park
- Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea
| | - 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
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46
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Papatheodoridis GV, Voulgaris T, Papatheodoridi M, Kim WR. Risk Scores for Hepatocellular Carcinoma in Chronic Hepatitis B: A Promise for Precision Medicine. Hepatology 2020; 72:2197-2205. [PMID: 32602980 DOI: 10.1002/hep.31440] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Revised: 05/13/2020] [Accepted: 06/15/2020] [Indexed: 02/06/2023]
Affiliation(s)
- George V Papatheodoridis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greeces
| | - Thodoris Voulgaris
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greeces
| | - Margarita Papatheodoridi
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greeces
| | - W Ray Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA
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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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48
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Tseng CH, Tseng CM, Wu JL, Hsu YC, El-Serag HB. Magnitude of and prediction for risk of hepatocellular carcinoma in patients with chronic hepatitis B taking entecavir or tenofovir therapy: A systematic review. J Gastroenterol Hepatol 2020; 35:1684-1693. [PMID: 32343431 DOI: 10.1111/jgh.15078] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Revised: 04/01/2020] [Accepted: 04/23/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIM Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) have been shown to reduce incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). This systematic review aims to evaluate the magnitude, change over time, and prediction of residual HCC risks in CHB patients treated with ETV/TDF therapy. METHODS Available literature was systematically reviewed through searches of PubMed and EMBASE databases from January 1, 2006 to September 1, 2019, to identify cohort studies that reported HCC incidence in CHB patients during ETV/TDF therapy. Studies were screened by title and abstract and then evaluated for eligibility in terms of full text. RESULTS We identified 141 studies for full-text review, and 34 were eligible for analysis. From 19 studies with data separated by cirrhosis status, the 5-year cumulative incidence of HCC was 0.5-6.9% in patients without cirrhosis, 4.5-21.6% in compensated cirrhosis, and 36.3-46.5% in decompensated cirrhosis. All four studies that addressed temporal changes in HCC risks consistently found the incidence rate decreased over time in patients with cirrhosis, although the findings were inconsistent in patients without cirrhosis. Six predictive scores were developed and validated to predict incident HCC during ETV/TDF therapy in CHB patients. Common scoring variables included age, sex, cirrhosis (fibrosis grade), and hepatic function. Conflicting results were reported in seven individual studies and two meta-analyses that compared ETV versus TDF. CONCLUSIONS The residual risk of HCC remains during ETV/TDF treatment in CHB patients with cirrhosis but declines over time. Risk stratification is attainable by validated predictive scores.
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Affiliation(s)
- Cheng-Hao Tseng
- Division of Gastroenterology and Hepatology, E-DA Cancer Hospital/I-Shou University, Kaohsiung, Taiwan.,Center for Liver Diseases and Division of Gastroenterology and Hepatology, E-DA Hospital/I-Shou University, Kaohsiung, Taiwan
| | - Chao-Ming Tseng
- Division of Gastroenterology and Hepatology, E-DA Cancer Hospital/I-Shou University, Kaohsiung, Taiwan.,Center for Liver Diseases and Division of Gastroenterology and Hepatology, E-DA Hospital/I-Shou University, Kaohsiung, Taiwan
| | - Jia-Ling Wu
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yao-Chun Hsu
- Division of Gastroenterology and Hepatology, E-DA Cancer Hospital/I-Shou University, Kaohsiung, Taiwan.,Center for Liver Diseases and Division of Gastroenterology and Hepatology, E-DA Hospital/I-Shou University, Kaohsiung, Taiwan.,School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Hashem B El-Serag
- Michael E. DeBakey Veterans Affairs Medical Center and Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine Houston, Houston, Texas, USA
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Liang LY, Wong VWS, Toyoda H, Tse YK, Yip TCF, Yuen BWY, Tada T, Kumada T, Lee HW, Lui GCY, Chan HLY, Wong GLH. Serum hepatitis B core-related antigen predicts hepatocellular carcinoma in hepatitis B e antigen-negative patients. J Gastroenterol 2020; 55:899-908. [PMID: 32556643 DOI: 10.1007/s00535-020-01700-z] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Accepted: 06/08/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND Hepatitis B core-related antigen (HBcrAg) is a novel serum viral marker. Recent studies showed that its level correlates with the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). We aimed to evaluate the accuracy of serum HBsAg and HBcrAg levels at baseline to predict HCC. METHODS 1400 CHB patients who received nucleos(t)ide analogues (NA) treatment since December 2005 were included. Their stored serum samples at baseline were retrieved to measure HBsAg and HBcrAg levels. The primary endpoint was the cumulative incidence of HCC. RESULTS 85 (6.1%) patients developed HCC during a mean (± SD) follow-up duration of 45 ± 20 months. Serum HBcrAg level above 2.9 log10 U/mL at baseline was an independent factor for HCC in hepatitis B e antigen (HBeAg)-negative patients by multivariable analysis (adjusted hazard ratio 2.13, 95% CI 1.10-4.14, P = 0.025). HBcrAg above 2.9 log10 U/mL stratified the risk of HCC in HBeAg-negative patients with high PAGE-B score (P = 0.024 by Kaplan-Meier analysis), and possibly in cirrhotic patients (P = 0.08). Serum HBsAg level did not show any correlation with the risk of HCC in all patients or any subgroups. CONCLUSION Serum HBcrAg level predicts the risk of HCC accurately in NA-treated HBeAg-negative CHB patients.
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Affiliation(s)
- Lilian Yan Liang
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, 9/F Prince of Wales Hospital, Shatin, Hong Kong
| | - Vincent Wai-Sun Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, 9/F Prince of Wales Hospital, Shatin, Hong Kong
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR
| | | | - Yee-Kit Tse
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, 9/F Prince of Wales Hospital, Shatin, Hong Kong
| | - Terry Cheuk-Fung Yip
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, 9/F Prince of Wales Hospital, Shatin, Hong Kong
| | - Becky Wing-Yan Yuen
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, 9/F Prince of Wales Hospital, Shatin, Hong Kong
| | | | | | - Hye-Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Grace Chung-Yan Lui
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, 9/F Prince of Wales Hospital, Shatin, Hong Kong
| | - Henry Lik-Yuen Chan
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, 9/F Prince of Wales Hospital, Shatin, Hong Kong
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR
| | - Grace Lai-Hung Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR.
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, 9/F Prince of Wales Hospital, Shatin, Hong Kong.
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR.
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50
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Voulgaris T, Papatheodoridi M, Lampertico P, Papatheodoridis GV. Clinical utility of hepatocellular carcinoma risk scores in chronic hepatitis B. Liver Int 2020; 40:484-495. [PMID: 31884726 DOI: 10.1111/liv.14334] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Revised: 11/28/2019] [Accepted: 12/15/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Several risk scores have been recently developed to predict hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients. We systematically assessed the performance of the available HCC risk scores. METHODS Literature search was performed to identify all published studies reporting development or external validation of HCC risk scores in CHB patients. RESULTS Until March 2019, 12 scores were developed in untreated Asian and 7 scores in treated Asian (n = 6) or Caucasian (n = 1) patients. All scores provided significant predictions for HCC development in the derivation and validation cohorts of their original studies (c-statistic: 0.76-0.95) and usually classified patients into low, medium and high HCC risk groups. Eleven independent studies and three studies developing their own scores have validated externally some scores in Asian (GAG-HCC:5, CU-HCC:6, REACH-B:6, REACH-Bm:4, LSM-HCC:3, PAGE-B:5) or Caucasian/mixed origin patients (GAG-HCC:4, CU-HCC:4, REACH-B:4, PAGE-B:2). All scores offered acceptable predictability in almost all independent Asian cohorts (c-statistic: 0.70-0.86), but only PAGE-B and recently modified PAGE-B (mPAGE-B) offered good predictability in all independent Caucasian and/or Asian cohorts. Negative predictive values for 5-year HCC prediction were ≤99% (95%-99%) in most independent cohorts assessing Asian risk scores and 99%-100% in all independent cohorts (Caucasian/mixed origin:2; Asian:3) assessing PAGE-B and/or recently mPAGE-B. CONCLUSIONS Direct comparison of the newest HCC risk scores in independent patient cohorts of different origin remains intriguing, although statistical associations may not be directly transferable to clinical practice. PAGE-B and recently mPAGE-B score seem to offer persistently high predictability for Caucasian and/or Asian treated patients with low HCC risk who require no surveillance.
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Affiliation(s)
- Thodoris Voulgaris
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - Margarita Papatheodoridi
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - Pietro Lampertico
- Division of Gastroenterology and Hepatology, CRC "A. M. and A. Migliavacca" Center for the Study of Liver Disease, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - George V Papatheodoridis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
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