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1
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Block PD, Lim JK. Unmet needs in the clinical management of chronic hepatitis B infection. J Formos Med Assoc 2024:S0929-6646(24)00388-7. [PMID: 39155176 DOI: 10.1016/j.jfma.2024.08.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 08/13/2024] [Accepted: 08/14/2024] [Indexed: 08/20/2024] Open
Abstract
The hepatitis B virus (HBV) remains a global problem despite effective tools to prevent, diagnosis, and control it. Unmet needs are identifiable across its clinical care cascade, underlining the challenges providers face in delivering effective care for patients with chronic hepatitis B. The review herein will focus on three timely clinical issues in HBV. This includes efforts to optimize delivery of perinatal HBV care, improve HBV-related hepatocellular carcinoma risk stratification models, and clarify the role of finite therapy in the HBV treatment algorithm. Important developments within these three topics will be addressed with the goal to motivate further investigation and optimization of these treatment strategies for HBV.
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Affiliation(s)
- Peter D Block
- Section of Digestive Diseases and Yale Liver Center, Yale School of Medicine, USA
| | - Joseph K Lim
- Section of Digestive Diseases and Yale Liver Center, Yale School of Medicine, USA.
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Lani L, Stefanini B, Trevisani F. Surveillance for Hepatocellular Carcinoma in Patients with Successfully Treated Viral Disease of the Liver: A Systematic Review. Liver Cancer 2024; 13:376-388. [PMID: 39114761 PMCID: PMC11305665 DOI: 10.1159/000535497] [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] [Received: 08/08/2023] [Accepted: 11/23/2023] [Indexed: 08/10/2024] Open
Abstract
Background Surveillance for hepatocellular carcinoma (HCC) has been proven to increase the proportion of tumors detected at early stages and the chance of receiving curative therapies, reducing mortality by about 30%. Summary Current recommendations consist of a semi-annual abdominal ultrasound with or without serum alpha-fetoprotein measurement in patients with cirrhosis and specific subgroups of populations with chronic viral hepatitis. Antiviral therapies, such as nucleot(s)ide analogs that efficiently suppress the replication of hepatitis B virus (HBV) and direct-acting antiviral drugs able to eliminate the hepatitis C virus (HCV) in >90% of patients, have radically changed the outcomes of viral liver disease and decreased, but not eliminated, the risk of HCC in both cirrhotic and non-cirrhotic patients. HCC risk is a key starting point for implementing a cost-effective surveillance and should also guide the decision-making process concerning its modality. As the global number of effectively treated viral patients continues to rise, there is a pressing need to identify those for whom the benefit-to-harm ratio of surveillance is favorable and to determine how to conduct cost-effective screening on such patients. Key Messages This article addresses this topic and attempts to determine which patients should continue HCC surveillance after HBV suppression or HCV eradication, based on cost-effectiveness principles and the fact that HCC risk declines over time. We also formulate a proposal for a surveillance algorithm that switches the use of surveillance for HCC from the "one-size-fits-all" approach to individualized programs based on oncologic risk (precision surveillance).
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Affiliation(s)
- Lorenzo Lani
- Unit of Semeiotics, Liver, and Alcohol-related diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Benedetta Stefanini
- Unit of Semeiotics, Liver, and Alcohol-related diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Franco Trevisani
- Unit of Semeiotics, Liver, and Alcohol-related diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
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Pastras P, Zazas E, Kalafateli M, Aggeletopoulou I, Tsounis EP, Kanaloupitis S, Zisimopoulos K, Kottaridou EEK, Antonopoulou A, Drakopoulos D, Diamantopoulou G, Tsintoni A, Thomopoulos K, Triantos C. Predictive Risk Factors and Scoring Systems Associated with the Development of Hepatocellular Carcinoma in Chronic Hepatitis B. Cancers (Basel) 2024; 16:2521. [PMID: 39061161 PMCID: PMC11274905 DOI: 10.3390/cancers16142521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Revised: 07/04/2024] [Accepted: 07/09/2024] [Indexed: 07/28/2024] Open
Abstract
Chronic hepatitis B (CHB) infection constitutes a leading cause of hepatocellular carcinoma (HCC) development. The identification of HCC risk factors and the development of prognostic risk scores are essential for early diagnosis and prognosis. The aim of this observational, retrospective study was to evaluate baseline risk factors associated with HCC in CHB. Six hundred thirty-two consecutive adults with CHB (n = 632) [median age: 46 (IQR: 24)], attending the outpatients' Hepatology clinics between 01/1993-09/2020 were evaluated. Core promoter mutations and cirrhosis-HCC (GAG-HCC), Chinese University-HCC (CU-HCC), risk estimation for hepatocellular carcinoma in chronic hepatitis B (REACH-B), Fibrosis-4 (FIB-4), and Platelet Age Gender-HBV (PAGE-B) prognostic scores were calculated, and receiver operating curves were used to assess their prognostic performance. HCC was developed in 34 (5.38%) patients. In the multivariable Cox regression analysis, advanced age (HR: 1.086, 95% CI: 1.037-1.137), male sex (HR: 7.696, 95% CI: 1.971-30.046), alcohol abuse (HR: 2.903, 95% CI: 1.222-6.987) and cirrhosis (HR: 21.239, 95% CI: 6.001-75.167) at baseline were independently associated with the development of HCC. GAG-HCC and PAGE-B showed the highest performance with c-statistics of 0.895 (95% CI: 0.829-0.961) and 0.857 (95% CI: 0.791-0.924), respectively. In the subgroup of patients with cirrhosis, the performance of all scores declined. When treated and untreated patients were studied separately, the discriminatory ability of the scores differed. In conclusion, HCC development was independently associated with advanced age, male sex, alcohol abuse, and baseline cirrhosis among a diverse population with CHB. GAG-HCC and PAGE-B showed high discriminatory performance to assess the risk of HCC development in these patients, but these performances declined in the subgroup of patients with cirrhosis. Further research to develop scores more specific to certain CHB subgroups is needed.
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Affiliation(s)
- Ploutarchos Pastras
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, 26504 Patras, Greece; (P.P.); (E.Z.); (M.K.); (I.A.); (E.P.T.); (S.K.); (K.Z.); (E.-E.-K.K.); (A.A.); (D.D.); (G.D.); (K.T.)
| | - Evaggelos Zazas
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, 26504 Patras, Greece; (P.P.); (E.Z.); (M.K.); (I.A.); (E.P.T.); (S.K.); (K.Z.); (E.-E.-K.K.); (A.A.); (D.D.); (G.D.); (K.T.)
| | - Maria Kalafateli
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, 26504 Patras, Greece; (P.P.); (E.Z.); (M.K.); (I.A.); (E.P.T.); (S.K.); (K.Z.); (E.-E.-K.K.); (A.A.); (D.D.); (G.D.); (K.T.)
| | - Ioanna Aggeletopoulou
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, 26504 Patras, Greece; (P.P.); (E.Z.); (M.K.); (I.A.); (E.P.T.); (S.K.); (K.Z.); (E.-E.-K.K.); (A.A.); (D.D.); (G.D.); (K.T.)
| | - Efthymios P. Tsounis
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, 26504 Patras, Greece; (P.P.); (E.Z.); (M.K.); (I.A.); (E.P.T.); (S.K.); (K.Z.); (E.-E.-K.K.); (A.A.); (D.D.); (G.D.); (K.T.)
| | - Stavros Kanaloupitis
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, 26504 Patras, Greece; (P.P.); (E.Z.); (M.K.); (I.A.); (E.P.T.); (S.K.); (K.Z.); (E.-E.-K.K.); (A.A.); (D.D.); (G.D.); (K.T.)
| | - Konstantinos Zisimopoulos
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, 26504 Patras, Greece; (P.P.); (E.Z.); (M.K.); (I.A.); (E.P.T.); (S.K.); (K.Z.); (E.-E.-K.K.); (A.A.); (D.D.); (G.D.); (K.T.)
| | - Eirini-Eleni-Konstantina Kottaridou
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, 26504 Patras, Greece; (P.P.); (E.Z.); (M.K.); (I.A.); (E.P.T.); (S.K.); (K.Z.); (E.-E.-K.K.); (A.A.); (D.D.); (G.D.); (K.T.)
| | - Aspasia Antonopoulou
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, 26504 Patras, Greece; (P.P.); (E.Z.); (M.K.); (I.A.); (E.P.T.); (S.K.); (K.Z.); (E.-E.-K.K.); (A.A.); (D.D.); (G.D.); (K.T.)
| | - Dimosthenis Drakopoulos
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, 26504 Patras, Greece; (P.P.); (E.Z.); (M.K.); (I.A.); (E.P.T.); (S.K.); (K.Z.); (E.-E.-K.K.); (A.A.); (D.D.); (G.D.); (K.T.)
| | - Georgia Diamantopoulou
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, 26504 Patras, Greece; (P.P.); (E.Z.); (M.K.); (I.A.); (E.P.T.); (S.K.); (K.Z.); (E.-E.-K.K.); (A.A.); (D.D.); (G.D.); (K.T.)
| | - Aggeliki Tsintoni
- Department of Internal Medicine, University Hospital of Patras, 26504 Patras, Greece;
| | - Konstantinos Thomopoulos
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, 26504 Patras, Greece; (P.P.); (E.Z.); (M.K.); (I.A.); (E.P.T.); (S.K.); (K.Z.); (E.-E.-K.K.); (A.A.); (D.D.); (G.D.); (K.T.)
| | - Christos Triantos
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, 26504 Patras, Greece; (P.P.); (E.Z.); (M.K.); (I.A.); (E.P.T.); (S.K.); (K.Z.); (E.-E.-K.K.); (A.A.); (D.D.); (G.D.); (K.T.)
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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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5
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Ugonabo O, Udoh UAS, Rajan PK, Reeves H, Arcand C, Nakafuku Y, Joshi T, Finley R, Pierre SV, Sanabria JR. The Current Status of the Liver Liquid Biopsy in MASH Related HCC: Overview and Future Directions. Biomolecules 2023; 13:1369. [PMID: 37759769 PMCID: PMC10526956 DOI: 10.3390/biom13091369] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Revised: 09/03/2023] [Accepted: 09/07/2023] [Indexed: 09/29/2023] Open
Abstract
Metabolic dysfunction-associated steatohepatitis (MASH) is one of the major risk factors for chronic liver disease and hepatocellular carcinoma (HCC). The incidence of MASH in Western countries continues to rise, driving HCC as the third cause of cancer-related death worldwide. HCC has become a major global health challenge, partly from the obesity epidemic promoting metabolic cellular disturbances but also from the paucity of biomarkers for its early detection. Over 50% of HCC cases are clinically present at a late stage, where curative measures are no longer beneficial. Currently, there is a paucity of both specific and sensitive biological markers for the early-stage detection of HCC. The search for biological markers in the diagnosis of early HCC in high-risk populations is intense. We described the potential role of surrogates for a liver biopsy in the screening and monitoring of patients at risk for nesting HCC.
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Affiliation(s)
- Onyinye Ugonabo
- Department of Medicine, Marshall University School of Medicine, Marshall University, Huntington, WV 25701, USA; (O.U.); (T.J.)
| | - Utibe-Abasi Sunday Udoh
- Marshall Institute for Interdisciplinary Research, Marshall University School of Medicine, Huntington, WV 25703, USA; (U.-A.S.U.); (P.K.R.); (Y.N.); (S.V.P.)
- Department of Surgery, Marshall University School of Medicine, Marshall University, Huntington, WV 25701, USA; (H.R.); (C.A.); (R.F.)
| | - Pradeep Kumar Rajan
- Marshall Institute for Interdisciplinary Research, Marshall University School of Medicine, Huntington, WV 25703, USA; (U.-A.S.U.); (P.K.R.); (Y.N.); (S.V.P.)
- Department of Surgery, Marshall University School of Medicine, Marshall University, Huntington, WV 25701, USA; (H.R.); (C.A.); (R.F.)
| | - Heather Reeves
- Department of Surgery, Marshall University School of Medicine, Marshall University, Huntington, WV 25701, USA; (H.R.); (C.A.); (R.F.)
| | - Christina Arcand
- Department of Surgery, Marshall University School of Medicine, Marshall University, Huntington, WV 25701, USA; (H.R.); (C.A.); (R.F.)
| | - Yuto Nakafuku
- Marshall Institute for Interdisciplinary Research, Marshall University School of Medicine, Huntington, WV 25703, USA; (U.-A.S.U.); (P.K.R.); (Y.N.); (S.V.P.)
- Department of Surgery, Marshall University School of Medicine, Marshall University, Huntington, WV 25701, USA; (H.R.); (C.A.); (R.F.)
| | - Tejas Joshi
- Department of Medicine, Marshall University School of Medicine, Marshall University, Huntington, WV 25701, USA; (O.U.); (T.J.)
| | - Rob Finley
- Department of Surgery, Marshall University School of Medicine, Marshall University, Huntington, WV 25701, USA; (H.R.); (C.A.); (R.F.)
| | - Sandrine V. Pierre
- Marshall Institute for Interdisciplinary Research, Marshall University School of Medicine, Huntington, WV 25703, USA; (U.-A.S.U.); (P.K.R.); (Y.N.); (S.V.P.)
| | - Juan Ramon Sanabria
- Marshall Institute for Interdisciplinary Research, Marshall University School of Medicine, Huntington, WV 25703, USA; (U.-A.S.U.); (P.K.R.); (Y.N.); (S.V.P.)
- Department of Surgery, Marshall University School of Medicine, Marshall University, Huntington, WV 25701, USA; (H.R.); (C.A.); (R.F.)
- Department of Nutrition and Metabolomic Core Facility, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
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6
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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: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 08/25/2022] [Accepted: 08/28/2022] [Indexed: 12/08/2022]
Abstract
Hepatocellular carcinoma (HCC) mortality remains high primarily due to late diagnosis as a consequence of failed early detection. Professional societies recommend semi-annual HCC screening in at-risk patients with chronic liver disease to increase the likelihood of curative treatment receipt and improve survival. However, recent dynamic shift of HCC etiologies from viral to metabolic liver diseases has significantly increased the potential target population for the screening, whereas annual incidence rate has become substantially lower. Thus, with the contemporary HCC etiologies, the traditional screening approach might not be practical and cost-effective. HCC screening consists of (i) definition of rational at-risk population, and subsequent (ii) repeated application of early detection tests to the population at regular intervals. The suboptimal performance of the currently available HCC screening tests highlights an urgent need for new modalities and strategies to improve early HCC detection. In this review, we overview recent developments of clinical, molecular, and imaging-based tools to address the current challenge, and discuss conceptual framework and approaches of their clinical translation and implementation. These encouraging progresses are expected to transform the current "one-size-fits-all" HCC screening into individualized precision approaches to early HCC detection and ultimately improve the poor HCC prognosis in the foreseeable future.
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Affiliation(s)
- Yi-Te Lee
- California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, California
| | - Naoto Fujiwara
- Liver Tumor Translational Research Program, Simmons Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Ju Dong Yang
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California; Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, Los Angeles, California; Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Yujin Hoshida
- Liver Tumor Translational Research Program, Simmons Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
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Lin CL, Wu SY, Lai MW, Hsu CW, Chen WM, Jao AT, Chien CH, Hu CC, Chien RN, Yeh CT. Predicting Hepatocellular Carcinoma Risk in Chronic Hepatitis B Patients Receiving Finite Periods of Antiviral Therapy. Cancers (Basel) 2023; 15:3343. [PMID: 37444453 DOI: 10.3390/cancers15133343] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 06/08/2023] [Accepted: 06/20/2023] [Indexed: 07/15/2023] Open
Abstract
PURPOSE Hepatocellular carcinoma (HCC) is one of the most severe complications in chronic hepatitis B virus (HBV) infection. HCC can still develop in patients with chronic HBV (CHB) infection undergoing antiviral therapy. Several effective scoring systems for the prediction of HCC risk in CHB patients have been established. However, very few of them are designed for CHB patients receiving nucleos(t)ide analogues (NAs) therapy. Furthermore, none are available for HCC risk prediction in CHB patients receiving finite periods of antiviral therapy. METHODS This study enrolled 790 consecutive treatment-naïve patients with CHB infection who had visited our liver clinics from 2008 to 2012 for pretreatment assessment before receiving antiviral therapies. The treatments were provided at finite periods according to the National Health Insurance Policy in Taiwan. The last follow-up date was 31 December 2021. We analyzed the virological and clinical factors in these 790 CHB patients receiving finite periods of NA treatments and identified the most significant risk factors for HCC to establish a novel predictive scoring system. By using stepwise selection in a multivariate Cox proportional hazards model, we divided the patients into three risk groups. RESULTS Our predictive scoring system included five independent variables: genotype C (adjusted HR [aHR] = 2.23), NA-withdraw-related hepatitis relapse (aHR = 6.96), male (aHR = 4.19), liver cirrhosis (aHR = 11.14), and T1768A core promoter mutation (aHR = 3.21). This model revealed significant differences in HCC incidence among the three risk groups. The 5-year cumulative HCC risk significantly differed among the three risk groups (low risk: 1.33%, moderate risk: 4.99%, and high risk: 17.46%), with log-rank test p < 0.001. CONCLUSION Our predictive scoring system is a promising tool for the prediction of HCC in CHB patients receiving finite NA treatments. Genotype C, NA-withdraw-related hepatitis relapse, male gender, liver cirrhosis, and the T1768A HBV core promoter mutation were significant independent risk factors.
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Affiliation(s)
- Chih-Lang Lin
- Liver Research Center, Department of Gastroenterology and Hepatology, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan
- Community Medicine Research Center, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan
- College of Medicine, Chang Gung University, Taoyua 833, Taiwan
| | - Szu-Yuan Wu
- Graduate Institute of Business Administration, College of Management, Fu Jen Catholic University, New Taipei City 242, Taiwan
- Artificial Intelligence Development Center, Fu Jen Catholic University, New Taipei City 242, Taiwan
- Big Data Center, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan 265, Taiwan
- Department of Food Nutrition and Health Biotechnology, College of Medical and Health Science, Asia University, Taichung 413, Taiwan
- Division of Radiation Oncology, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan 265, Taiwan
- Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung 413, Taiwan
- Centers for Regional Anesthesia and Pain Medicine, Taipei Municipal Wan Fang Hospital, Taipei Medical University, Taipei City 242, Taiwan
| | - Ming-Wei Lai
- College of Medicine, Chang Gung University, Taoyua 833, Taiwan
- Liver Research Center, Chang Gung Memorial Hospital, Taoyuan 833, Taiwan
- Division of Pediatric Gastroenterology, Department of Pediatrics, Linkou Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
| | - Chao-Wei Hsu
- College of Medicine, Chang Gung University, Taoyua 833, Taiwan
- Liver Research Center, Chang Gung Memorial Hospital, Taoyuan 833, Taiwan
| | - Wan-Ming Chen
- Liver Research Center, Chang Gung Memorial Hospital, Taoyuan 833, Taiwan
- Division of Pediatric Gastroenterology, Department of Pediatrics, Linkou Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
| | - An-Tzu Jao
- Graduate Institute of Business Administration, College of Management, Fu Jen Catholic University, New Taipei City 242, Taiwan
| | - Cheng-Hung Chien
- Liver Research Center, Department of Gastroenterology and Hepatology, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan
- Community Medicine Research Center, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan
- College of Medicine, Chang Gung University, Taoyua 833, Taiwan
| | - Ching-Chih Hu
- Liver Research Center, Department of Gastroenterology and Hepatology, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan
- College of Medicine, Chang Gung University, Taoyua 833, Taiwan
| | - Rong-Nan Chien
- College of Medicine, Chang Gung University, Taoyua 833, Taiwan
- Liver Research Center, Chang Gung Memorial Hospital, Taoyuan 833, Taiwan
| | - Chau-Ting Yeh
- College of Medicine, Chang Gung University, Taoyua 833, Taiwan
- Liver Research Center, Chang Gung Memorial Hospital, Taoyuan 833, Taiwan
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8
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Hou Y, Yu H, Zhang Q, Yang Y, Liu X, Wang X, Jiang Y. Machine learning-based model for predicting the esophagogastric variceal bleeding risk in liver cirrhosis patients. Diagn Pathol 2023; 18:29. [PMID: 36823660 PMCID: PMC9948468 DOI: 10.1186/s13000-023-01293-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Accepted: 01/13/2023] [Indexed: 02/25/2023] Open
Abstract
BACKGROUND Liver cirrhosis patients are at risk for esophagogastric variceal bleeding (EGVB). Herein, we aimed to estimate the EGVB risk in patients with liver cirrhosis using an artificial neural network (ANN). METHODS We included 999 liver cirrhosis patients hospitalized at the Beijing Ditan Hospital, Capital Medical University in the training cohort and 101 patients from Shuguang Hospital in the validation cohort. The factors independently affecting EGVB occurrence were determined via univariate analysis and used to develop an ANN model. RESULTS The 1-year cumulative EGVB incidence rates were 11.9 and 11.9% in the training and validation groups, respectively. A total of 12 independent risk factors, including gender, drinking and smoking history, decompensation, ascites, location and size of varices, alanine aminotransferase (ALT), γ-glutamyl transferase (GGT), hematocrit (HCT) and neutrophil-lymphocyte ratio (NLR) levels as well as red blood cell (RBC) count were evaluated and used to establish the ANN model, which estimated the 1-year EGVB risk. The ANN model had an area under the curve (AUC) of 0.959, which was significantly higher than the AUC for the North Italian Endoscopic Club (NIEC) (0.669) and revised North Italian Endoscopic Club (Rev-NIEC) indices (0.725) (all P < 0.001). Decision curve analyses revealed improved net benefits of the ANN compared to the NIEC and Rev-NIEC indices. CONCLUSIONS The ANN model accurately predicted the 1-year risk for EGVB in liver cirrhosis patients and might be used as a basis for risk-based EGVB surveillance strategies.
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Affiliation(s)
- Yixin Hou
- grid.24696.3f0000 0004 0369 153XCenter of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jingshun East Road, Beijing, 100051 China
| | - Hao Yu
- grid.24696.3f0000 0004 0369 153XCenter of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jingshun East Road, Beijing, 100051 China
| | - Qun Zhang
- grid.24696.3f0000 0004 0369 153XCenter of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jingshun East Road, Beijing, 100051 China
| | - Yuying Yang
- grid.412585.f0000 0004 0604 8558Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xiaoli Liu
- grid.24696.3f0000 0004 0369 153XCenter of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jingshun East Road, Beijing, 100051 China
| | - Xianbo Wang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jingshun East Road, Beijing, 100051, China.
| | - Yuyong Jiang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jingshun East Road, Beijing, 100051, China.
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Mitchell T, Nayagam JS, Dusheiko G, Agarwal K. Health inequalities in the management of chronic hepatitis B virus infection in patients from sub-Saharan Africa in high-income countries. JHEP REPORTS : INNOVATION IN HEPATOLOGY 2022; 5:100623. [PMID: 36636709 PMCID: PMC9829705 DOI: 10.1016/j.jhepr.2022.100623] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/07/2022] [Revised: 10/21/2022] [Accepted: 10/24/2022] [Indexed: 11/06/2022]
Abstract
Chronic hepatitis B virus disproportionately affects migrant communities in high-income countries, reflecting increased migration from sub-Saharan Africa. Chronic hepatitis B virus is endemic in sub-Saharan Africa, yet the natural history of chronic infection experienced by patients remains incompletely understood, with evidence of variability across genotypes and regions within sub-Saharan Africa. Clinical guidelines recommending treatment thresholds are not specific to sub-Saharan African patients and are based on natural history studies from Western Pacific Asian countries. Access to standard of care treatment is available for sub-Saharan African people with chronic hepatitis B virus infection in high-income countries; however, the evidence base for these treatments was not established in this cohort and areas of uncertainty remain, particularly regarding HCC surveillance and treatment discontinuation. Participation in phase III clinical trials for chronic hepatitis B therapies is almost non-existent amongst sub-Saharan African patients, even when residing in high-income countries that participate in multicentre trials. Engagement with sub-Saharan African patients with chronic hepatitis B in high-income countries is challenging because of the stigma associated with the diagnosis, absence of routine screening systems and the complexities involved in navigating the healthcare system. Nonetheless, improved engagement is critical if we are to achieve global hepatitis B virus elimination.
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Affiliation(s)
- Tim Mitchell
- Institute of Liver Studies, King’s College Hospital, London, United Kingdom,Gastroenterology and Hepatology Department, Royal Perth Hospital, Perth, Australia,Corresponding author. Address: Gastroenterology and Hepatology Department, Level 8 A Block, Royal Perth Hospital, 197 Wellington Street, Perth, Western Australia 6000, Australia; Tel.: +61 8 9224 2179.
| | - Jeremy S. Nayagam
- Institute of Liver Studies, King’s College Hospital, London, United Kingdom,Department of Inflammation Biology, King’s College London, London, UK
| | - Geoffrey Dusheiko
- Institute of Liver Studies, King’s College Hospital, London, United Kingdom,University College London Medical School, London, UK
| | - Kosh Agarwal
- Institute of Liver Studies, King’s College Hospital, London, United Kingdom
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10
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Spearman CW, Dusheiko G, Jonas E, Abdo A, Afihene M, Cunha L, Desalegn H, Kassianides C, Katsidzira L, Kramvis A, Lam P, Lesi OA, Micah EA, Musabeyezu E, Ndow G, Nnabuchi CV, Ocama P, Okeke E, Rwegasha J, Shewaye AB, Some FF, Tzeuton C, Sonderup MW. Hepatocellular carcinoma: measures to improve the outlook in sub-Saharan Africa. Lancet Gastroenterol Hepatol 2022; 7:1036-1048. [PMID: 35810766 DOI: 10.1016/s2468-1253(22)00041-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2021] [Revised: 01/26/2022] [Accepted: 02/02/2022] [Indexed: 02/08/2023]
Abstract
Hepatocellular carcinoma is a leading public health concern in sub-Saharan Africa, and it is most prevalent in young adults (median 45 years [IQR 35-57]). Overall, outcomes are poor, with a median survival of 2·5 months after presentation. Major risk factors for hepatocellular carcinoma are hepatitis B virus (HBV), hepatitis C virus, aflatoxin B1 exposure, and alcohol consumption, with metabolic dysfunction-associated fatty liver disease slowly emerging as a risk factor over the past few years. Crucially, these risk factors are preventable and manageable with effective implementation of the HBV birth-dose vaccination, treatment of chronic viral hepatitis, provision of harm reduction services, and by decreasing aflatoxin B1 exposure and harmful alcohol consumption. Primary prevention is central to the management of hepatocellular carcinoma, especially in poorly resourced environments. Effective screening and surveillance programmes with recall policies need to be implemented, because detection and curative management of hepatocellular carcinoma is possible if it is detected at an early stage, even in countries with minimal resources, with appropriate upskilling of medical personnel. The establishment of centres of excellence with advanced diagnostic and therapeutic capabilities within countries should improve hepatocellular carcinoma outcomes and assist in driving the implementation of much needed systematic data systems focused on hepatocellular carcinoma to establish the accurate burden in sub-Saharan Africa. Such data would support the public health importance of hepatocellular carcinoma and provide a strong basis for advocacy, programme development, resource allocation, and monitoring of progress in reducing mortality.
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Affiliation(s)
- C Wendy Spearman
- Division of Hepatology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
| | - Geoffrey Dusheiko
- University College London Medical School, London, UK; Kings College Hospital, London, UK
| | - Eduard Jonas
- Surgical Gastroenterology Unit, Division of General Surgery, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
| | - Abdelmounem Abdo
- National Centre for Gastrointestinal and Liver Disease, Ibn Sina Hospital, Alamarat, Khartoum, Sudan
| | - Mary Afihene
- Department of Medicine, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | - Lina Cunha
- Gastroenterology Unit, Maputo Private Hospital, Maputo, Mozambique
| | - Hailemichael Desalegn
- Department of Internal Medicine, St Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia
| | - Chris Kassianides
- Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
| | - Leolin Katsidzira
- Internal Medicine Unit, Faculty of Medicine and Health Sciences, University of Zimbabwe, Harare, Zimbabwe
| | - Anna Kramvis
- Hepatitis Virus Diversity Research Unit, Department of Internal Medicine, School of Clinical Medicine, University of the Witwatersrand, Johannesburg, South Africa
| | | | - Olufunmilayo A Lesi
- Gastroenterology and Hepatology Unit, College of Medicine, University of Lagos, Lagos, Nigeria
| | - Eileen A Micah
- Department of Medicine, Komfo Anokye Teaching Hospital, Kumasi, Ghana
| | | | - Gibril Ndow
- Disease Control and Elimination Theme, MRC Unit The Gambia at the London School of Tropical Medicine, London, UK; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Chidi V Nnabuchi
- Asokoro District Hospital, Nile University Teaching Hospital, Abuja, Nigeria
| | - Ponsiano Ocama
- School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
| | - Edith Okeke
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, College of Health Sciences, University of Jos, Jos University Teaching Hospital, Jos, Nigeria
| | - John Rwegasha
- Gastroenterology Training Centre, Department of Internal Medicine, Muhimbili National Hospital, Dar Es Salaam, Tanzania
| | - Abate B Shewaye
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Fatuma F Some
- Department of Medicine, School of Medicine, College of Health Sciences, Moi University, Eldoret, Kenya
| | - Christian Tzeuton
- Faculty of Medicine and Pharmaceutical Sciences of Douala, University of Douala, Douala, Cameroon
| | - Mark W Sonderup
- Division of Hepatology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
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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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13
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Stella L, Santopaolo F, Gasbarrini A, Pompili M, Ponziani FR. Viral hepatitis and hepatocellular carcinoma: From molecular pathways to the role of clinical surveillance and antiviral treatment. World J Gastroenterol 2022; 28:2251-2281. [PMID: 35800182 PMCID: PMC9185215 DOI: 10.3748/wjg.v28.i21.2251] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Revised: 12/08/2021] [Accepted: 04/26/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a global health challenge. Due to the high prevalence in low-income countries, hepatitis B virus (HBV) and hepatitis C virus infections remain the main risk factors for HCC occurrence, despite the increasing frequencies of non-viral etiologies. In addition, hepatitis D virus coinfection increases the oncogenic risk in patients with HBV infection. The molecular processes underlying HCC development are complex and various, either independent from liver disease etiology or etiology-related. The reciprocal interlinkage among non-viral and viral risk factors, the damaged cellular microenvironment, the dysregulation of the immune system and the alteration of gut-liver-axis are known to participate in liver cancer induction and progression. Oncogenic mechanisms and pathways change throughout the natural history of viral hepatitis with the worsening of liver fibrosis. The high risk of cancer incidence in chronic viral hepatitis infected patients compared to other liver disease etiologies makes it necessary to implement a proper surveillance, both through clinical-biochemical scores and periodic ultrasound assessment. This review aims to outline viral and microenvironmental factors contributing to HCC occurrence in patients with chronic viral hepatitis and to point out the importance of surveillance programs recommended by international guidelines to promote early diagnosis of HCC.
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Affiliation(s)
- Leonardo Stella
- Internal Medicine and Gastroenterology, Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome 00168, Italy
| | - Francesco Santopaolo
- Internal Medicine and Gastroenterology, Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome 00168, Italy
| | - Antonio Gasbarrini
- Internal Medicine and Gastroenterology, Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome 00168, Italy
| | - Maurizio Pompili
- Internal Medicine and Gastroenterology, Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome 00168, Italy
| | - Francesca Romana Ponziani
- Internal Medicine and Gastroenterology, Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome 00168, Italy
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Rattananukrom C, Kitiyakara T. Comparison between using hepatocellular carcinoma (
HCC
) risk scores and the
HCC
national guideline to identify high‐risk chronic hepatitis B patients for
HCC
surveillance in Thailand. JGH Open 2022; 6:408-420. [PMID: 35774347 PMCID: PMC9218522 DOI: 10.1002/jgh3.12753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Revised: 04/20/2022] [Accepted: 04/25/2022] [Indexed: 11/08/2022]
Affiliation(s)
- Chitchai Rattananukrom
- Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Srinagarind Hospital Khon Kaen University Khon Kaen Thailand
| | - Taya Kitiyakara
- Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital Mahidol University Bangkok Thailand
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15
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Verification of hepatitis B-related hepatocellular carcinoma predictive models to evaluate the risk of HCC in patients with liver cirrhosis under antiviral treatment. Eur J Gastroenterol Hepatol 2022; 34:546-552. [PMID: 35170528 DOI: 10.1097/meg.0000000000002302] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. The development of chronic hepatitis B (CHB)-related HCC can be attributed to continuous hepatitis B virus (HBV) infection. It is crucial to identify and monitor patients with CHB at high risk of HCC occurrence so that HCC can be detected early and the patients are able to receive effective treatment promptly to increase the survival rate and improve prognosis. AIM This study aimed to verify hepatitis B-related hepatocellular carcinoma predictive models to evaluate the risk of HCC in patients with liver cirrhosis under antiviral treatment. METHODS Patients with HBV-related compensated cirrhosis were treated with lamivudine and adefovir randomly, and then with a combination of two drugs at different time points based on the virologic response. Patients with HCC occurrence during follow-up were categorized as HCC group, whereas others as control group. They were further divided into 2-year HCC, 2-year control, 5-year HCC, and 5-year control groups according to the observation time. The operating curves of the patients were used to verify models before and after antiviral treatment. RESULTS Using the baseline as a parameter, the area under the curve (AUC) of risk estimation for hepatocellular carcinoma in chronic hepatitis B (REACH-B) after 2 and 5 years was 0.863 and 0.797, respectively. The AUC after 2 and 5 years was 0.839 and 0.747, respectively, for guide with age, gender, HBV DNA, core promoter mutations and cirrhosis (GAG-HCC) and 0.741 and 0.748, respectively, for Taiwanese HBV cohort (TW1). Using 48 weeks as the parameter, it has an optimal critical value of 8 points. The AUC of REACH-B after 2 and 5 years was 0.738 and 0.721, respectively. CONCLUSION REACH-B can predict the risk of HCC occurrence in patients with compensated liver cirrhosis before and after antiviral treatment. GAG-HCC and TW1 could predict the risk before antiviral treatment.
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Gokcen P, Guzelbulut F, Adali G, Degirmenci Salturk AG, Ozturk O, Bahadir O, Kanatsiz E, Kiyak M, Ozdil K, Doganay HL. Validation of the PAGE-B score to predict hepatocellular carcinoma risk in caucasian chronic hepatitis B patients on treatment. World J Gastroenterol 2022; 28:665-674. [PMID: 35317422 PMCID: PMC8900546 DOI: 10.3748/wjg.v28.i6.665] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Revised: 07/27/2021] [Accepted: 01/20/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Several risk scores have been developed to predict hepatocellular carcinoma (HCC) risk in chronic hepatitis B (CHB) patients. The majority of risk scores are based on pretreatment variables that are no longer considered risk factors for HCC development due to the suppression of hepatitis B virus replication early in the course of potent antiviral treatment in most patients. The PAGE-B score, which is based on platelet levels, age and sex, has been shown to accurately predict HCC risk in CHB patients on antiviral treatment in various populations.
AIM We aimed to evaluate the PAGE-B score in predicting HCC risk in Turkish CHB patients on antiviral treatment.
METHODS In this study, we recruited 742 CHB patients who had been treated with tenofovir disoproxil fumarate or entecavir for ≥ 1 year. Risk groups were determined according to the PAGE-B scores as follows: ≤ 9, low; 10-17, moderate and ≥ 18, high. The cumulative HCC incidences in each risk group were computed using Kaplan-Meier analysis and were compared using the log-rank test. The accuracy of the PAGE-B score in predicting HCC risk was evaluated using a time-dependent area under the receiver operating characteristic (AUROC) curve at all study time points. Univariate and multivariate logistic regression analyses were used to assess the risk factors for HCC development.
RESULTS The mean follow-up time was 54.7 ± 1.2 mo. HCC was diagnosed in 26 patients (3.5%). The cumulative HCC incidences at 1, 3, 5 and 10 years were 0%, 0%, 0% and 0.4% in the PAGE-B low-risk group; 0%, 1.2%, 1.5% and 2.1% in the PAGE-B moderate-risk group; and 5%, 11.7%, 12.5%, and 15% in the PAGE-B high-risk group, respectively (log-rank P < 0.001). The AUROCs of the PAGE-B score in the prediction of HCC development at 1, 3, 5 and 10 years were 0.977, 0.903, 0.903 and 0.865, respectively. In the multivariable analysis, older age, male sex, lower platelet levels, presence of cirrhosis, and absence of alanine aminotransferase normalization at month 6 were associated with HCC development (all P < 0.05).
CONCLUSION The PAGE-B score is a practical tool to predict HCC risk in Turkish patients with CHB and may be helpful to improve surveillance strategies.
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Affiliation(s)
- Pinar Gokcen
- Department of Gastroenterology, Health Sciences University, Umraniye Teaching and Research Hospital, Istanbul 34764, Turkey
| | - Fatih Guzelbulut
- Department of Gastroenterology, Health Sciences University, Haydarpasa Numune Teaching and Research Hospital, Istanbul 34668, Turkey
| | - Gupse Adali
- Department of Gastroenterology, Health Sciences University, Umraniye Teaching and Research Hospital, Istanbul 34764, Turkey
| | - Ayca Gokce Degirmenci Salturk
- Department of Gastroenterology, Health Sciences University, Haydarpasa Numune Teaching and Research Hospital, Istanbul 34668, Turkey
| | - Oguzhan Ozturk
- Department of Gastroenterology, Health Sciences University, Umraniye Teaching and Research Hospital, Istanbul 34764, Turkey
| | - Ozgur Bahadir
- Department of Gastroenterology, Health Sciences University, Haydarpasa Numune Teaching and Research Hospital, Istanbul 34668, Turkey
| | - Emine Kanatsiz
- Department of Gastroenterology, Health Sciences University, Haydarpasa Numune Teaching and Research Hospital, Istanbul 34668, Turkey
| | - Mevlut Kiyak
- Department of Gastroenterology, Health Sciences University, Haydarpasa Numune Teaching and Research Hospital, Istanbul 34668, Turkey
| | - Kamil Ozdil
- Department of Gastroenterology, Health Sciences University, Umraniye Teaching and Research Hospital, Istanbul 34764, Turkey
| | - Hamdi Levent Doganay
- Department of Gastroenterology, Health Sciences University, Umraniye Teaching and Research Hospital, Istanbul 34764, Turkey
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Development of hepatocellular carcinoma from various phases of chronic hepatitis B virus infection. PLoS One 2021; 16:e0261878. [PMID: 34962955 PMCID: PMC8714106 DOI: 10.1371/journal.pone.0261878] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2021] [Accepted: 12/11/2021] [Indexed: 12/19/2022] Open
Abstract
Background & aims There is insufficient data on the clinical course of chronic hepatitis B (CHB) patients in the immune-tolerant (IT) and immune-clearance, inactive (IC) phases over a long follow-up period. Design We enrolled 466 CHB patients from our historical cohort, including 56 IT+MA (mildly active), 134 IC, 230 with chronic active hepatitis (CH) and 46 with liver cirrhosis (LC), who were categorized to each phase by at least one year of follow-up period from the first visit to our hospital. We investigated long-term risks, and their factors, of developing hepatocellular carcinoma (HCC), and the transition between the clinical phases, especially in the IT+MA and IC groups. Results Of the 56 patients in the IT+MA group, 27 remained the IT+MA phase, but 29 transitioned to the CH phase and started nucleot(s)ide analogue (NA) treatment during the follow-up period. Meanwhile, of the 134 patients in the IC group, only 5 started NA treatment after progressing to the CH phase. The development of HCC from the IT+MA, IC, CH, and LC groups was observed in 2, 2, 9, and 20 cases, respectively. The cumulative incidence rates of developing HCC in the IT+MA, IC, CH, and LC groups were 9.9, 1.8, 3.0, and 53.1% at 10 years. In the CH and LC group, patients who developed HCC were older, had higher levels of FIB-4 index, M2BPGi, HBcrAg and AFP, and had lower levels of albumin and platelet counts. In CH patients, FIB-4 index levels were elevated at the diagnosis of HCC compared to baseline, whereas these decreased during the follow-up period in non-HCC patients. Conclusions HCC occurred at a certain rate among patients in the IT+MA and IC groups. Careful follow-up is required for CH patients with higher levels of FIB-4 index and/or M2BPGi because of the high incidence of HCC development. (299 words)
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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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Yi D, Wen-Ping W, Lee WJ, Meloni MF, Clevert DA, Cristina Chammas M, Tannapfel A, Forgione A, Dietrich CF. Hepatocellular carcinoma in the non-cirrhotic liver. Clin Hemorheol Microcirc 2021; 80:423-436. [PMID: 34842182 DOI: 10.3233/ch-211309] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Liver cirrhosis is an established high-risk factor for HCC and the majority of patients diagnosed with HCC have cirrhosis. However, HCC also arises in non-cirrhotic livers in approximately 20 %of all cases. HCC in non-cirrhotic patients is often clinically silent and surveillance is usually not recommended. HCC is often diagnosed at an advanced stage in these patients. Current information about HCC in patients with non-cirrhotic liver is limited. Here we review the current knowledge on epidemiology, clinical features and imaging features of those patiens.
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Affiliation(s)
- Dong Yi
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wang Wen-Ping
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Won Jae Lee
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Department of HealthScience and Technology and Medical Device Management and Research, Samsung Advanced Institute for Health Science and Technology, Sungkyunkwan University, Seoul, Republic of Korea
| | - Maria Franca Meloni
- Radiology Department of Interventional Ultrasound Casa di Cura Igea, Milano, Italy Department of Radiology, University of Wisconsin, Madison, WI, USA
| | - Dirk-Andre Clevert
- Department of Radiology, Interdisciplinary Ultrasound-Center, University ofMunich-Grosshadern Campus, Munich, Germany
| | - Maria Cristina Chammas
- Institute of Radiology, Hospital dasClínicas, School of Medicine, University of São Paulo, São Paulo, Brazil
| | | | - Antonella Forgione
- Division of Internal Medicine, Hepatobiliary andImmunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria diBologna, Bologna, Italy
| | - Christoph Frank Dietrich
- Department AllgemeineInnere Medizin (DAIM), Kliniken Beau Site, Salem und Permanence, Hirslanden, Bern, Switzerland
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20
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Zhang Q, Cai DC, Hu P, Ren H. Low-level viremia in nucleoside analog-treated chronic hepatitis B patients. Chin Med J (Engl) 2021; 134:2810-2817. [PMID: 34759219 PMCID: PMC8668013 DOI: 10.1097/cm9.0000000000001793] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Indexed: 12/14/2022] Open
Abstract
ABSTRACT Low-level viremia (LLV) was defined as persistent or intermittent episodes of detectable hepatitis B virus (HBV) DNA (<2000 IU/mL, detection limit of 10 IU/mL) after 48 weeks of antiviral treatment. Effective antiviral therapies for chronic hepatitis B (CHB) patients, such as entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF), have been shown to inhibit the replication of HBV DNA and prevent liver-related complications. However, even with long-term antiviral therapy, there are still a number of patients with persistent or intermittent LLV. At present, the research on LLV to address whether adversely affect the clinical outcome is limited, and the follow-up treatment for these patients is open to question. At the same time, the mechanism of LLV is not clear. In this review, we summarize the incidence of LLV, the association between LLV and long-term outcomes, possible mechanisms, and management strategies in these patient populations.
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Affiliation(s)
- Qian Zhang
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
- Department of Infectious Diseases, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550001, China
| | - Da-Chuan Cai
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Peng Hu
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Hong Ren
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
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21
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Roberts SK, Majeed A, Kemp W. Controversies in the Management of Hepatitis B: Hepatocellular Carcinoma. Clin Liver Dis 2021; 25:785-803. [PMID: 34593153 DOI: 10.1016/j.cld.2021.06.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Hepatitis B is the leading cause of hepatocellular cancer (HCC) worldwide. Untreated, annual HCC incidence rates in chronic hepatitis B subjects are 0.4% in noncirrhotics and 2% to 3% in cirrhotics. Surveillance with ultrasound with/without α-fetoprotein at 6-month intervals is recommended in at-risk persons including children. Antiviral therapy in chronic hepatitis B with entecavir or tenofovir significantly lowers the risk of HCC across all stages of liver disease, and lowers the risk of HCC recurrence following curative therapy. There are insufficient data to recommend use of tenofovir over entecavir in the prevention of de novo or recurrent HCC postcurative therapy.
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Affiliation(s)
- Stuart K Roberts
- The Alfred, 55 Commercial Road, Melbourne 3004, Australia; Monash University, Melbourne, Australia.
| | - Ammar Majeed
- The Alfred, 55 Commercial Road, Melbourne 3004, Australia; Monash University, Melbourne, Australia
| | - William Kemp
- The Alfred, 55 Commercial Road, Melbourne 3004, Australia; Monash University, Melbourne, Australia
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22
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Kaneko S, Kurosaki M, Inada K, Kirino S, Hayakawa Y, Yamashita K, Osawa L, Sekiguchi S, Higuchi M, Takaura K, Maeyashiki C, Tamaki N, Yasui Y, Itakura J, Takahashi Y, Tsuchiya K, Nakanishi H, Izumi N. Hepatitis B core-related antigen predicts disease progression and hepatocellular carcinoma in hepatitis B e antigen-negative chronic hepatitis B patients. J Gastroenterol Hepatol 2021; 36:2943-2951. [PMID: 34057248 DOI: 10.1111/jgh.15563] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 05/16/2021] [Accepted: 05/26/2021] [Indexed: 12/28/2022]
Abstract
BACKGROUND AND AIM The serum hepatitis B core-related antigen (HBcrAg) is considered a surrogate marker of the amount and activity of intrahepatic covalently closed circular DNA. This study aims to investigate the virological characteristics of HBcrAg in chronic hepatitis B (CHB) patients and to reveal the hepatocellular carcinoma (HCC) risk factors of hepatitis B e antigen (HBeAg)-negative patients. METHODS Hepatitis B core-related antigen was measured in 245 naive CHB patients before receiving nucleoside/nucleotide analog (NA) therapy. All patients were receiving NA (entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide) continuously for more than 1 year until the end of follow-up, and they did not have a history of HCC. Hepatitis B viral status was compared between 106 HBeAg-positive and 139 HBeAg-negative patients. RESULTS Median HBcrAg levels were significantly higher in HBeAg-positive patients than in HBeAg-negative patients (> 6.8 vs 3.7 log U/mL, P < 0.01). In HBeAg-negative patients, higher HBcrAg levels were associated with cirrhosis (119 chronic hepatitis/20 cirrhosis = 3.5/4.7 log U/mL, P = 0.03) and higher serum hepatitis B virus DNA. During a median follow-up of 5.28 (1.03-12.0) years, the 5-year cumulative HCC incidence rate was 5.4% in the HBeAg-negative cohort. In the multivariate Cox regression analysis, higher HBcrAg levels at 1 year were independent predictive factors for HCC development in HBeAg-negative patients who received NA therapy (cutoff value, 4.1 log U/mL; hazard ratio, 6.749; 95% confidence interval, 1.334-34.15, P < 0.01) and even in non-cirrhosis patients. CONCLUSION Hepatitis B core-related antigen was useful for understanding disease progression in CHB patients and for stratifying the risk for carcinogenesis in HBeAg-negative patients receiving NA therapy.
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Affiliation(s)
- Shun Kaneko
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Kento Inada
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Sakura Kirino
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yuka Hayakawa
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Koji Yamashita
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Leona Osawa
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Shuhei Sekiguchi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Mayu Higuchi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Kenta Takaura
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Chiaki Maeyashiki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Nobuharu Tamaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yutaka Yasui
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Jun Itakura
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yuka Takahashi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Kaoru Tsuchiya
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Hiroyuki Nakanishi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
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23
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Lou T, Li B, Xiong P, Jin C, Chen Y. External validation of hepatocellular carcinoma risk scores in patients with chronic hepatitis B virus infection in China. J Viral Hepat 2021; 28:1373-1380. [PMID: 34218498 DOI: 10.1111/jvh.13569] [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: 03/10/2021] [Revised: 04/18/2021] [Accepted: 06/19/2021] [Indexed: 02/06/2023]
Abstract
Several scores have been proposed in untreated or treated patients with chronic hepatitis B (CHB) to predict risks of hepatocellular carcinoma (HCC) occurrence. However, it is still unclear which score suits all chronic hepatitis B virus (HBV)-infected patients well, regardless of whether they are chronic carriers or CHB patients. In this study, we validated and compared the predictability of CU-HCC, REACH-B, PAGE-B and mPAGE-B in patients with chronic HBV infection in China. 1,786 patients with no history of HCC were recruited, with 978 carriers and 808 CHB patients on antiviral therapy. Patients were classified into low- and high-risk groups according to the predefined cut-off values of 5, 8, 10 and 9 for CU-HCC, REACH-B, PAGE-B and mPAGE-B. The median follow-up period was 43.7months, during which 18 (1.0%) patients developed HCC. The areas under the receiver operating characteristic curves (AUROCs) of CU-HCC, REACH-B, PAGE-B and mPAGE-B scores to predict HCC risk at 36 months were 0.815, 0.703, 0.794 and 0.825, respectively (all p < 0.05). No significant difference among AUROCs of these scores was observed except those of mPAGE-B and REACH-B at 36 months. The cumulative incidence of HCC in low- and high- risk groups based on CU-HCC, REACH-B, PAGE-B and mPAGE-B were 0.4% vs. 3.2%, 0.7% vs. 1.5%, 0.2% vs. 1.3%, and 0.2% vs. 1.7% at 36 months, respectively (all p < 0.05, except PAGE-B, log-rant test). Both CU-HCC and mPAGE-B scores accurately predict HCC risk in Chinese chronic HBV-infected patients. Patients with CU-HCC <5 or mPAGE-B <9 could be exempt from HCC surveillance within 36 months.
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Affiliation(s)
- Tao Lou
- Department of Infectious Diseases, The Fourth Affiliated Hospital Zhejiang University School of Medicine, Yiwu, Zhejiang Province, China
| | - Bin Li
- Department of Infectious Diseases, The Fourth Affiliated Hospital Zhejiang University School of Medicine, Yiwu, Zhejiang Province, China
| | - Pian Xiong
- Department of Infectious Diseases, The Fourth Affiliated Hospital Zhejiang University School of Medicine, Yiwu, Zhejiang Province, China
| | - Caiting Jin
- Department of Infectious Diseases, The Fourth Affiliated Hospital Zhejiang University School of Medicine, Yiwu, Zhejiang Province, China
| | - Yagang Chen
- Department of Infectious Diseases, The Fourth Affiliated Hospital Zhejiang University School of Medicine, Yiwu, Zhejiang Province, China
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24
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Lee HW, Yip TCF, Tse YK, Wong GLH, Kim BK, Kim SU, Park JY, Kim DY, Chan HLY, Ahn SH, Wong VWS. Hepatic Decompensation in Cirrhotic Patients Receiving Antiviral Therapy for Chronic Hepatitis B. Clin Gastroenterol Hepatol 2021; 19:1950-1958.e7. [PMID: 32889148 DOI: 10.1016/j.cgh.2020.08.064] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Revised: 08/24/2020] [Accepted: 08/27/2020] [Indexed: 02/06/2023]
Abstract
OBJECTIVES It is unclear if anti-hepatitis B virus (HBV) treatment can eliminate incident hepatic decompensation. Here we report the incidence and predictors of hepatic decompensation among cirrhotic patients receiving antiviral therapy for chronic hepatitis B. METHODS This is a post hoc analysis of two prospective HBV cohorts from Hong Kong and South Korea. Patients with liver stiffness measurement (LSM) ≥10 kPa and compensated liver disease at baseline were included. The primary endpoint was incident hepatic decompensation (jaundice or cirrhotic complications) with competing risk analysis. RESULTS 818 patients (mean age, 54.9 years; 519 male [63.4%]) were included in the final analysis. During a mean follow-up of 58.1 months, 32 (3.9%) patients developed hepatic decompensation, among whom 34% were secondary to HCC. Three (0.4%) patients experienced variceal bleeding alone, 27 (3.3%) had non-bleeding decompensation and 13 (1.6%) had more than 2 decompensating events Baseline LSM, diabetes, alanine aminotransferase, platelet, total bilirubin, albumin, prothrombin time, and eGFR were independent predictors of hepatic decompensation. 30/506 (5.9%) patients fulfilling the Baveno VI criteria (LSM ≥20 kPa and/or platelet count <150ⅹ109/L) and 2/312 (0.6%) patients not fulfilling the criteria developed hepatic decompensation (P < .001). CONCLUSIONS Hepatic decompensation is uncommon but not eliminated in patients receiving antiviral therapy for HBV-related cirrhosis, and only a third of decompensating events are secondary to HCC. The Baveno VI criteria, which was originally designed to detect varices needing treatment, can be effectively applied in this population to identify patients at risk of decompensation.
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Affiliation(s)
- Hye Won Lee
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea; Insitute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea; Liver Center, Severance Hospital, Seoul, South Korea
| | - Terry Cheuk-Fung Yip
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Yee-Kit Tse
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Grace Lai-Hung Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea; Insitute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea; Liver Center, Severance Hospital, Seoul, South Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea; Insitute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea; Liver Center, Severance Hospital, Seoul, South Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea; Insitute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea; Liver Center, Severance Hospital, Seoul, South Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea; Insitute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea; Liver Center, Severance Hospital, Seoul, South Korea
| | - Henry Lik-Yuen Chan
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea; Insitute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea; Liver Center, Severance Hospital, Seoul, South Korea.
| | - Vincent Wai-Sun Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China.
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25
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Reporting and Performance of Hepatocellular Carcinoma Risk Prediction Models: Based on TRIPOD Statement and Meta-Analysis. Can J Gastroenterol Hepatol 2021; 2021:9996358. [PMID: 34513751 PMCID: PMC8433031 DOI: 10.1155/2021/9996358] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Revised: 07/05/2021] [Accepted: 07/23/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The performance of risk prediction models for hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) was uncertain. The aim of the study was to critically evaluate the reports of transparent and external validation performances of these prediction models based on system review and meta-analysis. METHODS A systematic search of the Web of Science and PubMed was performed for studies published until October 17, 2020. The transparent reporting of a multivariable prediction model for the individual prognosis or diagnosis (TRIPOD) tool was used to critically evaluate the quality of external validation reports for six models (CU-HCC, GAG-HCC, PAGE-B, mPAGE-B, REACH-B, and mREACH-B). The area under the receiver operator characteristic curve (AUC) values was to estimate the pooled external validating performance based on meta-analysis. Subgroup analysis and metaregression were also performed to explore heterogeneity. RESULTS Our meta-analysis included 22 studies published between 2011 and 2020. The compliance of the included studies to TRIPOD ranged from 59% to 90% (median, 74%; interquartile range (IQR), 70%, 79%). The AUC values of the six models ranged from 0.715 to 0.778. In the antiviral therapy subgroups, the AUC values of mREACH-B, GAG-HCC, and mPAGE-B were 0.785, 0.760, and 0.778, respectively. In the cirrhosis subgroup, all models had poor discrimination performance (AUC < 0.7). CONCLUSIONS A full report of calibration and handling of missing values would contribute to a greater improvement in the quality of external validation reports for CHB-related HCC risk prediction. It was necessary to develop a specific HCC risk prediction model for patients with cirrhosis.
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Lok J, Agarwal K. Screening for Hepatocellular Carcinoma in Chronic Hepatitis B: An Update. Viruses 2021; 13:v13071333. [PMID: 34372539 PMCID: PMC8309969 DOI: 10.3390/v13071333] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 06/27/2021] [Accepted: 07/06/2021] [Indexed: 11/24/2022] Open
Abstract
(1) Background: Hepatocellular carcinoma (HCC) is an important cause of mortality in individuals with chronic hepatitis B infection, with screening of high-risk groups recommended in all major international guidelines. Our understanding of the risk factors involved has improved over time, encouraging researchers to develop models that predict future risk of HCC development. (2) Methods: A literature search of the PubMed database was carried out to identify studies that derive or validate models predicting HCC development in patients with chronic hepatitis B. Subsequently, a second literature search was carried out to explore the potential role of novel viral biomarkers in this field. (3) Results: To date, a total of 23 models have been developed predicting future HCC risk, of which 12 have been derived from cohorts of treatment-naïve individuals. Most models have been developed in Asian populations (n = 20), with a smaller number in Caucasian cohorts (n = 3). All of the models demonstrate satisfactory performance in their original derivation cohorts, but many lack external validation. In recent studies, novel viral biomarkers have demonstrated utility in predicting HCC risk in patients with chronic hepatitis B, amongst both treated and treatment-naïve patients. (4) Conclusion: Several models have been developed to predict the risk of HCC development in individuals with chronic hepatitis B infection, but many have not been externally validated outside of the Asian population. Further research is needed to refine these models and facilitate a more tailored HCC surveillance programme in the future.
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Affiliation(s)
- James Lok
- Department of Gastroenterology, St. George’s Hospital, London SW17 0QT, UK
- Correspondence:
| | - Kosh Agarwal
- Institute of Liver Studies, King’s College Hospital, London SE5 9RS, UK;
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27
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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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28
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Abd El Aziz MA, Sacco R, Facciorusso A. Nucleos(t)ide analogues and Hepatitis B virus-related hepatocellular carcinoma: A literature review. Antivir Chem Chemother 2021; 28:2040206620921331. [PMID: 32418480 PMCID: PMC7232045 DOI: 10.1177/2040206620921331] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Hepatitis B virus is mainly considered to cause hepatocellular carcinoma which is
the fourth leading cause of cancer-related mortality worldwide. Treatment of
Hepatitis B virus with nucleos(t)ide analogues can decrease the progression of
the disease and subsequently decreases the incidence of hepatocellular
carcinoma. In this review, we have discussed the different classes of
nucleos(t)ide analogues used in the treatment of Hepatitis B virus and their
relationship with the development of hepatocellular carcinoma. Furthermore, we
discussed the effect of treatment of Hepatitis B virus with Nucleoside analogues
(NAs) before, during and after surgery, chemoembolization, radiofrequency
ablation, and chemotherapy for the treatment of hepatocellular carcinoma.
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Affiliation(s)
| | - Rodolfo Sacco
- Department of Medical Sciences, Section of Gastroenterology, University of Foggia, Foggia Italy
| | - Antonio Facciorusso
- Department of Medical Sciences, Section of Gastroenterology, University of Foggia, Foggia Italy
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Hu J, Zhang ZQ, Zhu W, Wu ZR, You Y, Liu Y, Su DW, Wang YB, Gong JP. Comparison of clinicopathological traits and prognostic factors of hepatocellular carcinoma with and without cirrhotic background. Carcinogenesis 2021; 41:1576-1582. [PMID: 32188964 DOI: 10.1093/carcin/bgaa024] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2019] [Revised: 02/21/2020] [Accepted: 03/16/2020] [Indexed: 02/05/2023] Open
Abstract
The difference of the patients bearing hepatocellular carcinoma (HCC) with and without cirrhosis at clinical level has not been completely determined. This study compared their differences in clinicopathological traits and prognostic factors for relapse-free survival (RFS) and overall survival (OS). Animal model was established to validate the result of clinical observation. As a result, 82 patients bearing HCC with no cirrhosis (HCC-NC) and 146 patients bearing HCC with cirrhosis (HCC-C) were included. HCC-NC exhibited shorter prothrombin time and higher plasma albumin than HCC-C. In HCC-NC, satellite nodule was an independent risk factor for OS, and high γ-glutamyl transpeptidase was an independent risk factor for RFS. In HCC-C, female sex was an independent risk factor for OS. Stratified analysis showed the OS and RFS of HCC-NC were better than HCC-C in conditions like without cancer embolus (in the portal vein or bile duct), without lymphadenopathy in hepatic portal, without satellite nodule and with small or high-differentiated tumor. Animal model analysis showed HCC-NC had a higher liver/body weight ratio, less tumor count and smaller max tumor volume than HCC-C. In conclusion, clinicopathological traits and risk factors influencing postoperative OS and RFS differed between patients with HCC-C and HCC-NC.
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Affiliation(s)
- Jian Hu
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zhi-Qing Zhang
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Wei Zhu
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zhen-Ru Wu
- Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Yu You
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yan Liu
- Department of Gastroenterology, The Fifth People's Hospital of Chengdu, Chengdu, Sichuan Province, China
| | - Dai-Wen Su
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yun-Bing Wang
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jian-Ping Gong
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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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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32
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Chon HY, Lee JS, Lee HW, Chun HS, Kim BK, Park JY, Kim DY, Ahn SH, Kim SU. Impact of antiviral therapy on risk prediction model for hepatocellular carcinoma development in patients with chronic hepatitis B. Hepatol Res 2021; 51:406-416. [PMID: 33242365 DOI: 10.1111/hepr.13600] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Revised: 10/27/2020] [Accepted: 11/08/2020] [Indexed: 02/08/2023]
Abstract
AIM Risk prediction models for hepatocellular carcinoma (HCC) development are available. However, the influence of antiviral therapy (AVT) on these models in patients with chronic hepatitis B is unknown. METHODS The dynamic changes in risk prediction models during AVT and the association between risk prediction model and the risk of chronic hepatitis B-related HCC development were investigated. Between 2005 and 2017, 4917 patients with chronic hepatitis B (3361 noncirrhotic, 1556 cirrhotic) were recruited. RESULTS The mean age of the study population was 49.3 years and 60.6% (n = 2980) of the patients were male. The mean Chinese University-HCC (CU-HCC) score was 12.7 at baseline in the overall study population, and decreased significantly (mean, 8.7) after 1 year of AVT (p < 0.001). The score was maintained throughout 5 years of AVT (mean, 8.4-8.8; p > 0.05). The proportion of high-risk patients (CU-HCC score ≥ 20) was 28.9% at baseline, and decreased significantly after 1 year of AVT (5.0%; p < 0.001), and remained stable through 5 years of AVT (2.2%-3.6%; p > 0.05). In addition to the score at baseline, the CU-HCC score at 1 year of AVT independently predicted the risk of HCC development (hazard ratio = 1.072; p < 0.001), together with male gender and platelet count (all p < 0.05). CONCLUSIONS The CU-HCC score significantly decreased at 1 year of AVT and was maintained thereafter. The CU-HCC score after 1 year of AVT independently predicted the risk of HCC development in patients with chronic hepatitis B.
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Affiliation(s)
- Hye Yeon Chon
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Jae Seung Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Ho Soo Chun
- Department of Internal Medicine, 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
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
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Sinharay R, Grant AJ, Rivett L, Blackwell R, Mells G, Gelson W. Assessing efficacy of hepatocellular carcinoma prediction scores to prioritise hepatitis B surveillance in the COVID-19 era. GASTROHEP 2021; 3:80-87. [PMID: 33821150 PMCID: PMC8014760 DOI: 10.1002/ygh2.443] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Accepted: 01/25/2021] [Indexed: 02/07/2023]
Abstract
OBJECTIVE An estimated 250 million people worldwide are chronically infected with hepatitis B virus (HBV), the leading cause of hepatocellular carcinoma (HCC) globally. The novel Sars-cov2 virus continues to spread at an alarming rate, and with guidance at the onset of the pandemic recommending the deferral of HCC surveillance, the implications on liver cancer care are now emerging and highlight the urgent need for reorganisation of services. METHODS We analysed how five HCC risk prediction scores could aid stratification of patients with chronic HBV. We calculated scores using parameters measured from 3 years prior (where available, n = 17) and at the time of HCC diagnosis in all adult patients with chronic HBV diagnosed with HCC (n = 46), and controls (n = 100). We compared the number of patients requiring cancer surveillance according to each score and regional surveillance guidance. RESULTS The aMAP score had the highest discriminatory performance in HCC risk prediction at 3 years (area under receiver-operating characteristic curve (auROC) of 0.824), followed by the mREACH B score (auROC of 0.719), and mPAGE B score (auROC of 0.742). However, only the mREACH B score had a negative predictive value (NPV) >99%. Applying the mREACH B score to our HBV cohort identified 11 patients requiring HCC surveillance, compared with 62 under current guidelines. CONCLUSION The use of HCC risk prediction scores could streamline the surveillance of patients with chronic HBV at a time of extremely limited resources. Overall, the mREACH B score had both a strong discriminatory performance and a high NPV, thus safely identifying low risk patients not requiring surveillance.
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Affiliation(s)
- Ricky Sinharay
- Department of PathologyUniversity of CambridgeCambridgeUK
- Cambridge Liver UnitCambridge University Hospitals NHS Foundation TrustCambridgeUK
| | | | - Lucy Rivett
- Department of Infectious DiseasesCambridge University NHS Hospitals Foundation TrustCambridgeUK
- Clinical Microbiology and Public Health LaboratoryPublic Health EnglandCambridgeUK
| | - Rebecca Blackwell
- Cambridge Liver UnitCambridge University Hospitals NHS Foundation TrustCambridgeUK
| | - George Mells
- Cambridge Liver UnitCambridge University Hospitals NHS Foundation TrustCambridgeUK
| | - William Gelson
- Cambridge Liver UnitCambridge University Hospitals NHS Foundation TrustCambridgeUK
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Yip TCF, Wong GLH, Wong VWS. Negligible risk of hepatocellular carcinoma in chronic hepatitis B patients in immune-tolerant phase: Myth or fact. Clin Mol Hepatol 2021; 27:273-277. [PMID: 33517606 PMCID: PMC8046624 DOI: 10.3350/cmh.2021.0019] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Accepted: 01/29/2021] [Indexed: 12/12/2022] Open
Affiliation(s)
- Terry Cheuk-Fung Yip
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong SAR, China.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China.,Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Grace Lai-Hung Wong
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong SAR, China.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China.,Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Vincent Wai-Sun Wong
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong SAR, China.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China.,Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
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35
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Chou R, Blazina I, Bougatsos C, Holmes R, Selph S, Grusing S, Jou J. Screening for Hepatitis B Virus Infection in Nonpregnant Adolescents and Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA 2020; 324:2423-2436. [PMID: 33320229 DOI: 10.1001/jama.2020.19750] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Importance A 2014 review for the US Preventive Services Task Force (USPSTF) found antiviral therapy for hepatitis B virus (HBV) infection associated with improved intermediate outcomes, although evidence on clinical outcomes was limited. Objective To update the 2014 HBV screening review in nonpregnant adolescents and adults to inform the USPSTF. Data Sources Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Ovid MEDLINE (2014 to August 2019); with surveillance through July 24, 2020. Study Selection Randomized clinical trials (RCTs) on screening and antiviral therapy; cohort studies on screening, antiviral therapy clinical outcomes, and the association between achieving intermediate outcomes after antiviral therapy and clinical outcomes. Data Extraction and Synthesis One investigator abstracted data; a second investigator checked accuracy. Two investigators independently assessed study quality. Random-effects profile likelihood meta-analysis was performed. Results Thirty trials and 20 cohort studies, with a total of 94 168 participants, were included. No study directly evaluated the effects of screening for HBV infection vs no screening on clinical outcomes such as mortality, hepatocellular carcinoma, or cirrhosis. Screening strategies that focused on risk factors such as ever having immigrated from high-prevalence countries and demographic and behavioral risk factors would identify nearly all HBV infection cases. In 1 study (n = 21 008), only screening immigrants from high-prevalence countries would miss approximately two-thirds of infected persons. Based on 18 trials (n = 2972), antiviral therapy compared with placebo or no treatment was associated with greater likelihood of achieving intermediate outcomes, such as virologic suppression and hepatitis B e-antigen (HBeAg) or hepatitis B surface antigen loss or seroconversion; the numbers needed to treat ranged from 2.6 for virologic suppression to 17 for HBeAg seroconversion. Based on 12 trials (n = 4127), first-line antiviral therapies were at least as likely as nonpreferred therapies to achieve intermediate outcomes. Based on 16 trials (n = 4809), antiviral therapy might be associated with improved clinical outcomes, but data were sparse and imprecise. Nine cohort studies (n = 3893) indicated an association between achieving an intermediate outcome following antiviral therapy and improved clinical outcomes but were heterogeneous (hazard ratios ranged from 0.07 to 0.87). Antiviral therapy was associated with higher risk of withdrawal due to adverse events vs placebo or no antiviral therapy. Conclusions and Relevance There was no direct evidence for the clinical benefits and harms of HBV screening vs no screening. Antiviral therapy for HBV infection was associated with improved intermediate outcomes and may improve clinical outcomes.
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Affiliation(s)
- Roger Chou
- Pacific Northwest Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology; Oregon Health & Science University, Portland
- Division of General Internal Medicine and Geriatrics; Oregon Health & Science University, Portland
| | - Ian Blazina
- Pacific Northwest Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology; Oregon Health & Science University, Portland
| | - Christina Bougatsos
- Pacific Northwest Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology; Oregon Health & Science University, Portland
| | - Rebecca Holmes
- Pacific Northwest Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology; Oregon Health & Science University, Portland
| | - Shelley Selph
- Pacific Northwest Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology; Oregon Health & Science University, Portland
- Department of Family Medicine, Oregon Health & Science University, Portland
| | - Sara Grusing
- Pacific Northwest Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology; Oregon Health & Science University, Portland
| | - Janice Jou
- Pacific Northwest Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology; Oregon Health & Science University, Portland
- Division of Gastroenterology and Hepatology; Oregon Health & Science University, Portland
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36
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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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37
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Yu L, Liu X, Jiang Y, Wang X, Wang X, Yang Z. Use of a Novel Thyroid-Stimulating Hormone Model for Predicting the Progression of Hepatocellular Carcinoma. Onco Targets Ther 2020; 13:11421-11431. [PMID: 33192075 PMCID: PMC7654545 DOI: 10.2147/ott.s275304] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Accepted: 10/14/2020] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Individuals with hepatocellular carcinoma (HCC) are at risk of tumor recurrence after surgical resection, which affects their survival. The aim of the present study was to establish a model for predicting tumor progression in patients with HCC. METHODS To develop and validate the efficacy of a novel prognostic model, a retrospective cohort with HCC (n = 1005) at Beijing Ditan Hospital was enrolled from January 2008 and June 2017. Furthermore, a prospective cohort (n = 77) was recruited to validate the association between thyroid-stimulating hormone (TSH) levels and tumor progression in patients with HCC. RESULTS The model used in predicting the progression of HCC included four variables (namely, Barcelona Clinic Liver Cancer [BCLC] stage, presence of portal vein tumor thrombus, alpha-fetoprotein level, and TSH level). The AUROC of the 1-year progression-free survival (PFS) model was 0.755 and 0.753 in the deriving cohort and validation cohort, respectively, and these values were significantly higher than those of the Child-Pugh score, Model for End-stage Liver Disease (MELD), tumor-lymph node-metastasis (TNM) staging system, Okuda classification, and CLIP score. A simple assessment using a nomogram showed the 1-year PFS rate of patients with HCC. In the prospective cohort, the KM curve showed that the high TSH level group had a shorter PFS than the low TSH level (p = 0.001). CONCLUSION The prognostic model of HCC progression was superior to other well-known classical tumor scoring systems. A high TSH level was correlated to poor outcome, particularly those with advanced HCC.
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Affiliation(s)
- Lihua Yu
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, People's Republic of China.,First Clinical Medical College, Beijing University of Chinese Medicine, Beijing 100029, People's Republic of China
| | - Xiaoli Liu
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, People's Republic of China
| | - Yuyong Jiang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, People's Republic of China
| | - Xinhui Wang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, People's Republic of China
| | - Xianbo Wang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, People's Republic of China
| | - Zhiyun Yang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, People's Republic of China
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Chon YE, Jung KS, Ha Y, Kim MN, Lee JH, Hwang SG, Ahn SH, Kim DY, Han KH, Park JY. High body mass index hinders fibrosis improvement in patients receiving long-term tenofovir therapy in hepatitis B virus-related cirrhosis. J Viral Hepat 2020; 27:1119-1126. [PMID: 32558181 DOI: 10.1111/jvh.13345] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2020] [Revised: 04/26/2020] [Accepted: 05/25/2020] [Indexed: 12/12/2022]
Abstract
Long-term suppression of hepatitis B virus with tenofovir (TDF) induces fibrosis regression, and repeated liver stiffness (LS) measurement can indicate the improvement of fibrosis. We aimed to investigate predictors for LS improvement assessed by changes in patients receiving long-term TDF therapy in chronic hepatitis B (CHB) with liver cirrhosis. CHB patients with histologically proven liver cirrhosis who received TDF as the first-line therapy from 2012 to 2015 were recruited. LS and controlled attenuation parameter (CAP) measurements were repeated at baseline and 3 years after therapy. Liver stiffness improvement was defined as a drop of LS value ≥30% from the baseline. A total of 131 patients were enrolled (mean age 51.4% and male 64.9%). After 3 years of TDF therapy, the mean LS value significantly improved (from 14.7 to 8.6 kPa, P < .001), and 96 (73.3%) patients have achieved LS improvement. Predictors associated with improvement of LS were low body mass index (BMI), HBeAg positivity, and low CAP value at baseline. In multivariate analysis, low BMI was a single factor independently associated with LS improvement (odds ratio 0.680, 95% CI 0.560-0.825, P < .001). Patients with BMI < 23.5, had a 1.96 times more chance of achieving LS improvement compared to those with BMI ≥ 23.5 (90.1% vs. 46.0%, P = .001). High BMI was a single significant factor hindering the fibrosis improvement in patients receiving long-term TDF therapy in CHB with liver cirrhosis. Life style modification and BMI reduction should be encouraged to enhance fibrosis improvement.
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Affiliation(s)
- Young Eun Chon
- Department of Internal Medicine, Institute of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam, Korea.,CHA Bundang Liver Center, CHA Bundang Hospital, Seongnam, Korea
| | - Kyu Sik Jung
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.,Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Yeonjung Ha
- Department of Internal Medicine, Institute of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam, Korea.,CHA Bundang Liver Center, CHA Bundang Hospital, Seongnam, Korea
| | - Mi Na Kim
- Department of Internal Medicine, Institute of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam, Korea.,CHA Bundang Liver Center, CHA Bundang Hospital, Seongnam, Korea
| | - Joo Ho Lee
- Department of Internal Medicine, Institute of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam, Korea.,CHA Bundang Liver Center, CHA Bundang Hospital, Seongnam, Korea
| | - Seong Gyu Hwang
- Department of Internal Medicine, Institute of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam, Korea.,CHA Bundang Liver Center, CHA Bundang Hospital, Seongnam, Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.,Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Do Young Kim
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.,Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Kwang-Hyub Han
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.,Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Jun Yong Park
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.,Yonsei Liver Center, Severance Hospital, Seoul, Korea
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Yip TCF, Lai JCT, Wong GLH. Secondary prevention for hepatocellular carcinoma in patients with chronic hepatitis B: are all the nucleos(t)ide analogues the same? J Gastroenterol 2020; 55:1023-1036. [PMID: 32974760 PMCID: PMC7567686 DOI: 10.1007/s00535-020-01726-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Accepted: 08/24/2020] [Indexed: 02/04/2023]
Abstract
Reducing the incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) is the key ultimate goal set in essentially all treatment guidelines. There has been solid evidence supporting the relationship between serum hepatitis B virus (HBV) DNA level and risk of HCC. Antiviral treatment with oral nucleos(t)ide analogues (NAs) leads to sustained viral suppression and hence is often adopted as the secondary prevention for HCC in CHB patients. The first-generation NA, lamivudine, reduced the risk of HCC at 3 years compared to placebo; yet, its high emergence of antiviral resistance has made it no longer recommended in the international guidelines. Recent heated debate is about the two current first-line NAs-entecavir and tenofovir disoproxil fumarate (TDF)-Are they just as good to reduce HCC risk in CHB patients? A handful of cohort studies show two different kinds of observations-TDF is better than entecavir in lowering HCC risk, or these two NAs have led to similarly low risk of HCC. Tenofovir alafenamide (TAF), a modified version of TDF higher rate of ALT normalization, would be another potent nucleotide analogue is the treatment of choice for secondary prevention for HCC.
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Affiliation(s)
- Terry Cheuk-Fung Yip
- Department of Medicine and Therapeutics, 9/F Prince of Wales Hospital, 30-32 NganShing Street, Shatin, Hong Kong SAR, China
- Medical Data Analytic Centre (MDAC), Hong Kong SAR, China
- Institute of Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Jimmy Che-To Lai
- Department of Medicine and Therapeutics, 9/F Prince of Wales Hospital, 30-32 NganShing Street, Shatin, Hong Kong SAR, China
- Medical Data Analytic Centre (MDAC), Hong Kong SAR, China
- Institute of Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics, 9/F Prince of Wales Hospital, 30-32 NganShing Street, Shatin, Hong Kong SAR, China.
- Medical Data Analytic Centre (MDAC), Hong Kong SAR, China.
- Institute of Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
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Su TH, Peng CY, Tseng TC, Yang HC, Liu CJ, Liu CH, Chen PJ, Chen DS, Kao JH. Serum Mac-2-Binding Protein Glycosylation Isomer at Virological Remission Predicts Hepatocellular Carcinoma and Death in Chronic Hepatitis B-Related Cirrhosis. J Infect Dis 2020; 221:589-597. [PMID: 31574141 DOI: 10.1093/infdis/jiz496] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Accepted: 09/27/2019] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND To investigate serum Mac-2-binding protein glycosylation isomer (M2BPGi) levels in predicting hepatocellular carcinoma (HCC) and mortality at virological remission (VR, HBV DNA <20 IU/mL) following antiviral therapy in chronic hepatitis B (CHB) patients with cirrhosis. METHODS This retrospective cohort study included patients with CHB-related Child-Pugh A cirrhosis undergoing long-term antiviral therapy. Serum M2BPGi levels were quantified and multivariable Cox proportional hazards regression models were used to identify risk predictors for HCC and death. RESULTS A total of 126 and 145 patients were included in the derivation and validation cohorts, respectively. The mean age was 56, and the mean M2BPGi level was 1.86 cut-off index (COI) in the derivation cohort. After adjustment for confounders, a higher M2BPGi level at VR significantly predicted HCC (hazard ratio [HR]: 1.58, 95% confidence interval [CI]: 1.19-2.10, P=0.002) and death (HR: 2.17, 95% CI: 1.02-4.62, P=0.044). The M2BPGi ≥3 COI significantly increased the risk of HCC and death in the derivation and validation cohorts. Serial M2BPGi levels declined significantly (P=0.0001) in non-HCC patients only, and remained significantly lower than those who developed HCC afterwards (P=0.039). CONCLUSIONS Serum M2BPGi levels at antiviral therapy-induced VR predict HCC development and death in patients with CHB-related Child-Pugh A cirrhosis.
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Affiliation(s)
- Tung-Hung Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Cheng-Yuan Peng
- School of Medicine, China Medical University, Taichung, Taiwan.,Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Tai-Chung Tseng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Hung-Chih Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chen-Hua Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Pei-Jer Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Ding-Shinn Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
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41
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Yang HI, Yeh ML, Wong GL, Peng CY, Chen CH, Trinh HN, Cheung KS, Xie Q, Su TH, Kozuka R, Lee DH, Ogawa E, Zhao C, Ning HB, Huang R, Li J, Zhang JQ, Ide T, Xing H, Iwane S, Takahashi H, Wong C, Wong C, Lin CH, Hoang J, Le A, Henry L, Toyoda H, Ueno Y, Gane EJ, Eguchi Y, Kurosaki M, Wu C, Liu C, Shang J, Furusyo N, Enomoto M, Kao JH, Yuen MF, Yu ML, Nguyen MH. Real-World Effectiveness From the Asia Pacific Rim Liver Consortium for HBV Risk Score for the Prediction of Hepatocellular Carcinoma in Chronic Hepatitis B Patients Treated With Oral Antiviral Therapy. J Infect Dis 2020; 221:389-399. [PMID: 31550363 DOI: 10.1093/infdis/jiz477] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Accepted: 09/13/2019] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Patients on oral antiviral (OAV) therapy remain at hepatocellular carcinoma (HCC) risk. Risk prediction tools distinguishing treated patients with residual HCC risk are limited. The aim of this study was to develop an accurate, precise, simple-to-use HCC risk score using routine clinical variables among a treated Asian cohort. METHODS Adult Asian chronic hepatitis B (CHB) patients on OAV were recruited from 25 centers in the United States and the Asia-Pacific region. Excluded persons were coinfected with hepatitis C, D, or human immunodeficiency virus, had HCC before or within 1 year of study entry, or their follow-up was <1 year. Patients were randomized to derivation and validation cohorts on a 2:1 ratio. Statistically significant predictors from multivariate modeling formed the Real-world Effectiveness from the Asia Pacific Rim Liver Consortium for HBV (REAL-B) score. RESULTS A total of 8048 patients were randomized to the derivation (n = 5365) or validation group (n = 2683). The REAL-B model included 7 variables (male gender, age, alcohol use, diabetes, baseline cirrhosis, platelet count, and alpha fetoprotein), and scores were categorized as follows: 0-3 low risk, 4-7 moderate risk, and 8-13 high risk. Area under receiver operating characteristics were >0.80 for HCC risk at 3, 5, and 10 years, and these were significantly higher than other risk models (p < .001). CONCLUSIONS The REAL-B score provides 3 distinct risk categories for HCC development in Asian CHB patients on OAV guiding HCC surveillance strategy.
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Affiliation(s)
- Hwai-I Yang
- Genomics Research Center, Academia Sinica, Taipei, Taiwan.,Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Ming-Lun Yeh
- Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Grace L Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
| | - Cheng-Yuan Peng
- Department of Gastroenterology, China Medical University Hospital, Taichung, Taiwan
| | - Chien-Hung Chen
- Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Huy N Trinh
- San Jose Gastroenterology, San Jose, California, USA
| | - Ka-Shing Cheung
- Department of Medicine, The University of Hong Kong, Hong Kong
| | - Qing Xie
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, Peopole's Republic of China
| | - Tung-Hung Su
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Ritsuzo Kozuka
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Dong-Hyun Lee
- Department of Gastroenterology, Good Gang-An Hospital, Busan, South Korea
| | - Eiichi Ogawa
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Changqing Zhao
- Department of Cirrhosis, Institute of Liver Disease, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, Peopole's Republic of China
| | - Hui-Bin Ning
- Department of Infectious Diseases, Henan Provincial People's Hospital, Zhengzhou, Peopole's Republic of China
| | - Rui Huang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, Peopole's Republic of China
| | - Jiayi Li
- Palo Alto Medical Foundation, Mountain View Division, Mountain View, California, USA
| | - Jian Q Zhang
- Chinese Hospital, San Francisco, California, USA
| | - Tatsuya Ide
- Department of Internal Medicine, Kurume University School of Medicine, Fukuoka, Japan
| | - Huichun Xing
- Beijing Ditan Hospital, Capital Medical University, Beijing, Peopole's Republic of China
| | - Shinji Iwane
- Department of Internal Medicine, Saga University Hospital, Saga, Japan
| | | | | | | | - Chia-Hsin Lin
- Department of Gastroenterology, China Medical University Hospital, Taichung, Taiwan
| | - Joseph Hoang
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California, USA
| | - An Le
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California, USA
| | - Linda Henry
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California, USA
| | - Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Yoshiyuki Ueno
- Department of Gastroenterology, Yamagata University, Yamagata, Japan
| | - Edward J Gane
- Liver Transplant Unit, University of Auckland, Auckland, New Zealand
| | - Yuichiro Eguchi
- Department of Internal Medicine, Saga University Hospital, Saga, Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Chao Wu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, Peopole's Republic of China
| | - Chenghai Liu
- Department of Cirrhosis, Institute of Liver Disease, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, Peopole's Republic of China
| | - Jia Shang
- Department of Infectious Diseases, Henan Provincial People's Hospital, Zhengzhou, Peopole's Republic of China
| | - Norihiro Furusyo
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Masaru Enomoto
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Jia-Horng Kao
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Man-Fung Yuen
- Department of Medicine, The University of Hong Kong, Hong Kong
| | - Ming-Lung Yu
- Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California, USA
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Yip TCF, Lee HW, Wong VWS, Wong GLH, Tse YK, Lui GCY, Ahn SH, Chan HLY. Factors associated with improvement in MELD score after antiviral treatment in patients with chronic hepatitis B. J Gastroenterol Hepatol 2020; 35:1610-1618. [PMID: 32032974 DOI: 10.1111/jgh.15007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Revised: 02/05/2020] [Accepted: 02/05/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS Improvement in Model for End-Stage Liver Disease (MELD) score during antiviral treatment is associated with reduced hepatic decompensation and death in patients with chronic hepatitis B (CHB)-related cirrhosis. We aimed to identify factors associated with transplant-free survival and on-treatment MELD score improvement. METHODS We identified patients with CHB-related cirrhosis and MELD score ≥ 15 at the start of entecavir and/or tenofovir disoproxil fumarate treatment between 2005 and 2017. The primary endpoint was transplant-free survival at month 6. The secondary endpoints at month 6 were transplant-free survival with > 5-point improvement in MELD score and transplant-free survival with MELD score < 15. RESULTS Of 999 cirrhotic CHB patients, 605 (60.6%) achieved transplant-free survival at month 6. Proportion of transplant-free survival at month 6 stabilized at 10% in patients with high MELD. Patients who achieved transplant-free survival at month 6 were younger, had lower MELD score, lower alanine aminotransferase (ALT), and higher albumin at baseline. Of 605 patients with transplant-free survival, 276 (45.6%) achieved > 5-point improvement in MELD score; 183 (30.2%) had 1-point to 5-point improvement in MELD score; 146 (24.1%) had no improvement or a worsened MELD score. Also, 321 (53.1%) patients with transplant-free survival had a MELD score < 15 at month 6. CONCLUSION On top of lower MELD score, patients with CHB-related cirrhosis who are younger, have higher albumin, and lower ALT are more likely to achieve transplant-free survival after 6 months of antiviral treatment.
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Affiliation(s)
- Terry Cheuk-Fung Yip
- Faculty of Medicine, Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Hye Won Lee
- Faculty of Medicine, Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong.,Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Vincent Wai-Sun Wong
- Faculty of Medicine, Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Grace Lai-Hung Wong
- Faculty of Medicine, Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Yee-Kit Tse
- Faculty of Medicine, Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Grace Chung-Yan Lui
- Faculty of Medicine, Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Henry Lik-Yuen Chan
- Faculty of Medicine, Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
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Yip TCF, Liang LY, Wong GLH. Assessment of HCC Risk in Patients with Chronic HBV (REACH, PAGE-B, and Beyond). CURRENT HEPATOLOGY REPORTS 2020; 19:285-292. [DOI: 10.1007/s11901-020-00526-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]
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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: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [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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Temporal matrix completion with locally linear latent factors for medical applications. Artif Intell Med 2020; 107:101883. [PMID: 32828441 DOI: 10.1016/j.artmed.2020.101883] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2018] [Revised: 02/19/2020] [Accepted: 05/20/2020] [Indexed: 11/20/2022]
Abstract
Regular medical records are useful for medical practitioners to analyze and monitor patient's health status especially for those with chronic disease. However, such records are usually incomplete due to unpunctuality and absence of patients. In order to resolve the missing data problem over time, tensor-based models have been developed for missing data imputation in recent papers. This approach makes use of the low-rank tensor assumption for highly correlated data in a short-time interval. Nevertheless, when the time intervals are long, data correlation may not be high between consecutive time stamps so that such assumption is not valid. To address this problem, we propose to decompose matrices with missing data over time into their latent factors. Then, the locally linear constraint is imposed on the latent factors for temporal matrix completion. By using three publicly available medical datasets and two medical datasets collected from Prince of Wales Hospital in Hong Kong, experimental results show that the proposed algorithm achieves the best performance compared with state-of-the-art methods.
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Detectable HBV DNA during nucleos(t)ide analogues stratifies predictive hepatocellular carcinoma risk score. Sci Rep 2020; 10:13021. [PMID: 32747646 PMCID: PMC7400741 DOI: 10.1038/s41598-020-69522-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Accepted: 06/05/2020] [Indexed: 02/08/2023] Open
Abstract
Nucleos(t)ide analogs (NA) suppress hepatitis B virus (HBV) replication and reduce the risk of hepatocellular carcinoma (HCC). However, NA cannot suppress carcinogenesis completely in patients with chronic hepatitis B. The aims of this study were to identify risk factors for HCC and develop a refined carcinogenesis prediction model. Patients receiving NA therapy (n = 1,183) were recruited retrospectively from the 16 hospitals. All patients had been receiving NA continuously for more than 1 year until the end of the follow-up. During a median follow-up of 4.9 (1.0–12.9) years, 52 (4.4%) patients developed HCC. A multivariate analysis revealed that male gender, older age, lower platelet counts at the baseline, and detectable HBV DNA during NA therapy were independent predictive factors of HCC development. The PAGE-B score was calculated by using these factors. 240 (20.3%), 661 (55.9%), and 282 (23.8%) patients were classified into low-, intermediate-, and high-risk groups, respectively. In the intermediate- and high-risk group, detectable HBV DNA was significantly associated with a higher risk of HCC development compared with continuously undetectable HBV DNA, respectively (HR 3.338; 95% CI 1.045–10.66/HR 3.191; 95% CI 1.543–6.597). PAGE-B–DNA, which is the combined PAGE-B and HBV DNA status, was valuable for a more refined stratification of PAGE-B.
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Reply to: "Clinical relevance of dynamic risk assessment for developing hepatocellular carcinoma during prolonged antiviral therapy". J Hepatol 2020; 73:223-224. [PMID: 32229038 DOI: 10.1016/j.jhep.2020.03.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Accepted: 03/08/2020] [Indexed: 12/04/2022]
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48
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Yip TCF, Wong GLH, Wong VWS, Tse YK, Liang LY, Hui VWK, Lee HW, Lui GCY, Chan HLY. Reassessing the accuracy of PAGE-B-related scores to predict hepatocellular carcinoma development in patients with chronic hepatitis B. J Hepatol 2020; 72:847-854. [PMID: 31857194 DOI: 10.1016/j.jhep.2019.12.005] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Revised: 11/18/2019] [Accepted: 12/02/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS PAGE-B and modified PAGE-B (mPAGE-B) scores were developed to predict the risk of hepatocellular carcinoma (HCC) in patients on nucleos(t)ide analogue therapy. However, how and when to use these risk scores in clinical practice is uncertain. METHODS Consecutive adult patients with chronic hepatitis B who had received entecavir or tenofovir for at least 6 months between January 2005 and June 2018 were identified from a territory-wide database in Hong Kong. The performance of PAGE-B and mPAGE-B scores for HCC prediction at 5 years was assessed by area under the time-dependent receiver operating characteristic curve (AUROC), and different cut-off values of these 2 scores were evaluated by survival analysis. RESULTS Of 32,150 identified patients with chronic hepatitis B, 20,868 (64.9%) were male. Their mean age was 53.0 ± 13.2 years. At a median (IQR) follow-up of 3.9 (1.8-5.0) years, 1,532 (4.8%) patients developed HCC. The AUROCs (95% CI) for the prediction of HCC at 5 years were 0.77 (0.76-0.78) and 0.80 (0.79-0.81), with PAGE-B and mPAGE-B scores, respectively (p <0.001). A total of 9,417 (29.3%) patients were classified as having a low HCC risk by either PAGE-B or mPAGE-B scores; their 5-year cumulative incidence of HCC was 0.6% (0.4%-0.8%). This classification achieved a negative predictive value of 99.5% (99.4%-99.7%) to exclude patients without HCC development at 5 years. The AUROCs for the prediction of HCC with PAGE-B and mPAGE-B scores were similar at baseline and after 2 years on treatment. CONCLUSIONS PAGE-B and mPAGE-B scores can be applied to identify patients on antiviral therapy who are at low risk of developing HCC. These patients could be exempted from HCC surveillance due to their very low HCC risk. LAY SUMMARY Risk scores have been developed to predict the likelihood of patients with chronic hepatitis B developing hepatocellular carcinoma (HCC). We investigated the role of 2 such scores, PAGE-B and modified PAGE-B, in predicting the risk of HCC in 32,150 nucleos(t)ide analogue-treated patients with chronic hepatitis B. These scores identified a group of patients at very low risk of developing HCC who could therefore be exempted from HCC surveillance.
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Affiliation(s)
- Terry Cheuk-Fung Yip
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Grace Lai-Hung Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Vincent Wai-Sun Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Yee-Kit Tse
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Lilian Yan Liang
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Vicki Wing-Ki Hui
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Hye Won Lee
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Grace Chung-Yan Lui
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Henry Lik-Yuen Chan
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China.
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Tseng TC, Peng CY, Hsu YC, Su TH, Wang CC, Liu CJ, Yang HC, Yang WT, Lin CH, Yu ML, Lai HC, Tanaka Y, Nguyen MH, Liu CH, Chen PJ, Chen DS, Kao JH. Baseline Mac-2 Binding Protein Glycosylation Isomer Level Stratifies Risks of Hepatocellular Carcinoma in Chronic Hepatitis B Patients with Oral Antiviral Therapy. Liver Cancer 2020; 9:207-220. [PMID: 32399434 PMCID: PMC7206589 DOI: 10.1159/000504650] [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: 09/12/2019] [Accepted: 11/08/2019] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND AND AIMS Mac-2 binding protein glycosylation isomer (M2BPGi) is a novel biomarker correlating with liver fibrosis stages. However, little is known about how it predicts risks of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients receiving long-term antiviral treatment. MATERIALS AND METHODS The study contained 2 parts. The first part was to explore whether M2BPGi could be an HCC predictor in 899 CHB patients receiving long-term entecavir therapy. The second part was to validate the findings in an independent cohort of 384 on-treatment CHB patients with more severe liver disease. RESULTS In the discovery cohort, there were 64 patients developing HCC within an average follow-up of 7.01 years. Our data showed that M2BPGi level was positively associated with HCC development. When stratifying the patients by an M2BPGi level of 1.73 (the third quartile), the high M2BPGi group was shown to have an increased HCC risk compared to the low M2BPGi group with hazard ratio of 5.80 (95% CI 3.50-9.60). Furthermore, we found that the M2BPGi level complements PAGE-B score, a well-validated HCC prediction model, to predict HCC development. Lastly, the cutoff was validated in the independent cohort, especially those with an intermediate PAGE-B score. CONCLUSIONS In CHB patients receiving long-term antiviral treatment, serum M2BPGi level not only serves as an independent HCC predictor but also complements PAGE-B in stratifying HCC risks.
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Affiliation(s)
- Tai-Chung Tseng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Cheng-Yuan Peng
- School of Medicine, China Medical University, Taichung, Taiwan,Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Yao-Chun Hsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan
| | - Tung-Hung Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chia-Chi Wang
- Division of Gastroenterology, Department of Internal Medicine, Taipei Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, Taipei, Taiwan,School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Chun-Jen Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Hung-Chih Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan,Department of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Wan-Ting Yang
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chia-Hsin Lin
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Hsueh-Chou Lai
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Yasuhito Tanaka
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Mindie H. Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
| | - Chen-Hua Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Pei-Jer Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Ding-Shinn Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan,Genomics Research Center Academia Sinica, Taipei, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan,Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan,*Prof. Jia-Horng Kao, National Chair Professor, Ministry of Education and Distinguished Professor, Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, 1 Chang-Te Street, Taipei 10002 (Taiwan), E-Mail
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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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