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Jiang ML, Xu F, Li JL, Luo JY, Hu JL, Zeng XQ. Clinical features of abnormal α-fetoprotein in 15 patients with chronic viral hepatitis B after treatment with antiviral drugs. World J Hepatol 2025; 17:100392. [PMID: 39871898 PMCID: PMC11736481 DOI: 10.4254/wjh.v17.i1.100392] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Revised: 11/29/2024] [Accepted: 12/17/2024] [Indexed: 01/06/2025] Open
Abstract
BACKGROUND Liver function of chronic hepatitis B (CHB) patients is essentially normal after treatment with antiviral drugs. In rare cases, persistently abnormally elevated α-fetoprotein (AFP) is seen in CHB patients following long-term antiviral treatment. However, in the absence of imaging evidence of liver cancer, a reasonable explanation for this phenomenon is still lacking. AIM To explore the causes of abnormal AFP in patients with CHB who were not diagnosed with liver cancer. METHODS From November 2019 to May 2023, 15 patients with CHB after antiviral treatment and elevated AFP were selected. Clinical data and quality indicators related to laboratory testing, imaging data, and pathological data were obtained through inpatient medical records. RESULTS All patients had increased AFP and significantly elevated IgG. Cancer was excluded by imaging examination. Only four patients had elevated alanine aminotransferase, 10 had elevated aspartate aminotransferase, nine had elevated total bilirubin, and two had antinuclear antibodies. The liver biopsy and histopathological examination indicated that 14 patients had rosette, moderate, or higher interfacial inflammation, lymphocyte infiltration, and severe hepatic fibers (11 cases), which was consistent with the pathological features of autoimmune hepatitis (AIH). After 8-12 week of hormone therapy, the levels of AFP and IgG, and liver function returned to normal (P < 0.05). CONCLUSION For patients with CHB and elevated AFP after antiviral treatment, autoimmune hepatitis should be considered. CHB with AIH is clinically insidious and difficult to detect, and prone to progression to cirrhosis. Liver puncture pathological examination should be performed when necessary to confirm diagnosis.
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Affiliation(s)
- Man-Lei Jiang
- Ganzhou Institute of Liver Disease, Department of Hepatology, Ganzhou Fifth People's Hospital, Ganzhou 341000, Jiangxi Province, China.
| | - Fei Xu
- Ganzhou Institute of Liver Disease, Department of Hepatology, Ganzhou Fifth People's Hospital, Ganzhou 341000, Jiangxi Province, China
| | - Jin-Long Li
- Ganzhou Institute of Liver Disease, Department of Hepatology, Ganzhou Fifth People's Hospital, Ganzhou 341000, Jiangxi Province, China
| | - Jia-Yu Luo
- Ganzhou Institute of Liver Disease, Department of Hepatology, Ganzhou Fifth People's Hospital, Ganzhou 341000, Jiangxi Province, China
| | - Jiang-Ling Hu
- Ganzhou Institute of Liver Disease, Department of Hepatology, Ganzhou Fifth People's Hospital, Ganzhou 341000, Jiangxi Province, China
| | - Xian-Qiang Zeng
- Ganzhou Institute of Liver Disease, Department of Hepatology, Ganzhou Fifth People's Hospital, Ganzhou 341000, Jiangxi Province, China
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Reiberger T, Lens S, Cabibbo G, Nahon P, Zignego AL, Deterding K, Elsharkawy AM, Forns X. EASL position paper on clinical follow-up after HCV cure. J Hepatol 2024; 81:326-344. [PMID: 38845253 DOI: 10.1016/j.jhep.2024.04.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Accepted: 04/05/2024] [Indexed: 07/26/2024]
Abstract
Following the advent of direct-acting antivirals (DAAs), hepatitis C virus (HCV) infection can be cured in almost all infected patients. This has led to a number of clinical questions regarding the optimal management of the millions of patients cured of HCV. This position statement provides specific guidance on the appropriate follow-up after a sustained virological response in patients without advanced fibrosis, those with compensated advanced chronic liver disease, and those with decompensated cirrhosis. Guidance on hepatocellular carcinoma risk assessment and the management of extrahepatic manifestations of HCV is also provided. Finally, guidance is provided on the monitoring and treatment of reinfection in at-risk patients. The recommendations are based on the best available evidence and are intended to help healthcare professionals involved in the management of patients after treatment for HCV.
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Affiliation(s)
- Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
| | - Sabela Lens
- Liver Unit, Hospital Clinic Barcelona. IDIBAPS. Liver and Digestive Diseases Networking Biomedical Research Centre (CIBERehd). University of Barcelona. Spain
| | - Giuseppe Cabibbo
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties PROMISE, University of Palermo, Italy
| | - Pierre Nahon
- AP-HP, Hôpitaux Universitaires Paris Seine Saint-Denis, Liver Unit, Bobigny; Université Sorbonne Paris Nord, F-93000 Bobigny; Inserm, UMR-1138 "Functional Genomics of Solid Tumors", Centre de Recherche des Cordeliers, Université de Paris, France
| | - Anna Linda Zignego
- Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy
| | - Katja Deterding
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School. Germany
| | - Ahmed M Elsharkawy
- Liver Unit, Queen Elizabeth Hospital Birmingham. NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham, United Kingdom
| | - Xavier Forns
- Liver Unit, Hospital Clinic Barcelona. IDIBAPS. Liver and Digestive Diseases Networking Biomedical Research Centre (CIBERehd). University of Barcelona. Spain.
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Reappraisal of the roles of alpha-fetoprotein in hepatocellular carcinoma surveillance using large-scale nationwide database and hospital-based information. J Formos Med Assoc 2022; 121:2085-2092. [PMID: 35450743 DOI: 10.1016/j.jfma.2022.04.001] [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: 08/29/2021] [Revised: 03/22/2022] [Accepted: 04/05/2022] [Indexed: 11/24/2022]
Abstract
BACKGROUND/PURPOSE Controversies over the use of alpha-fetoprotein (AFP) for detection of hepatocellular carcinoma (HCC) existed from guidelines. Using large-scale database and hospital-based information, we aimed to reappraise the role of AFP in HCC surveillance, including proportion of AFP elevation by stage of HCC, additional benefit of AFP in combination of ultrasonography (US) in the detection of early HCC, and survival in early HCC with high AFP levels. METHODS This retrospective study enrolled 43,437 patients from database of the Taiwan Cancer Registry (TCR) and 4250 patients from Kaohsiung Chang Gung Memorial Hospital (KCGMH) between January 2011 and December 2017. RESULTS The HCC cases in KCGMH accounted for 9.8% of the total cases in the TCR. Among both nationwide database and hospital-based information, the proportion of early HCC patients with an AFP level of ≥20 ng/mL was approximately 40%. In KCGMH, the proportion of patients with an AFP level of ≥20 ng/mL and a virus-related (hepatitis B and C) etiology was around 41.7%; furthermore, among patients with early HCC, those with an AFP level of ≥20 ng/mL had 4.7 years of median survival and 48.3% of the 5-year overall survival rate. By hospital electronic medical records review of early HCC cohort in KCGMH, approximately 10.9% of patients with AFP levels ≥20 ng/mL had US-undetectable early HCC. CONCLUSION This study suggested that AFP in combination with US would add an additional benefit as being a prompted role for detection of early HCC in patients with US-undetectable HCC.
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Wang R, Wu H, Qi M, Han J, Ren Z. Bovine Serum Albumin Detection by Graphene Oxide Coated Long-Period Fiber Grating. PHOTONIC SENSORS 2022; 12:220305. [PMCID: PMC8783190 DOI: 10.1007/s13320-022-0649-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 11/23/2021] [Indexed: 06/17/2023]
Abstract
A biosensor for bovine serum albumin (BSA) detection by graphene oxide (GO) functionalized micro-taped long-period fiber grating (GMLPG) was demonstrated. The amide bond connected between the GO and BSA enabled the BSA to attach onto the fiber surface, which changed the effective refractive index of the cladding mode and characterized the concentration of the BSA. This real-time monitoring system demonstrated a sensing sensitivity of 1.263 nm/(mg/mL) and a detection limit of 0.043 mg/mL. Moreover, it illustrated superior measurement performance of higher sensitivity in the presence of glucose and urea as the interference, which showed static sensitivities of ∼1.476 nm/(mg/mL) and 1.504 nm/(mg/mL), respectively. The proposed GMLPG demonstrated a great potential for being employed as a sensor for biomedical and biochemical applications.
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Affiliation(s)
- Ruiduo Wang
- The State Key Laboratory of Photoelectric Technology and Functional Materials, International Collaborative Center on Photoelectric Technology and Nano Functional Materials, Institute of Photonics & Photon Technology, Northwest University, Xi’an, 710127 China
- The State Key Laboratory of Transient Optics and Photonics, Xi’an Institute of Optics and Precision Mechanics, Chinese Academy of Sciences, Xi’an, 710119 China
| | - Hao Wu
- The State Key Laboratory of Photoelectric Technology and Functional Materials, International Collaborative Center on Photoelectric Technology and Nano Functional Materials, Institute of Photonics & Photon Technology, Northwest University, Xi’an, 710127 China
| | - Mei Qi
- The School of Information Science and Technology, Northwest University, Xi’an, 710127 China
| | - Jing Han
- The State Key Laboratory of Photoelectric Technology and Functional Materials, International Collaborative Center on Photoelectric Technology and Nano Functional Materials, Institute of Photonics & Photon Technology, Northwest University, Xi’an, 710127 China
| | - Zhaoyu Ren
- The State Key Laboratory of Photoelectric Technology and Functional Materials, International Collaborative Center on Photoelectric Technology and Nano Functional Materials, Institute of Photonics & Photon Technology, Northwest University, Xi’an, 710127 China
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Sun F, Liu Z, Wang B. Correlation between low-level viremia and hepatitis B-related hepatocellular carcinoma and recurrence: a retrospective study. BMC Cancer 2021; 21:1103. [PMID: 34649509 PMCID: PMC8515654 DOI: 10.1186/s12885-021-08483-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Accepted: 06/11/2021] [Indexed: 12/15/2022] Open
Abstract
Background Low-level viremia generally refers to detectable HBV DNA levels lower than 2000 IU/mL. Studies show that low-level viremia is a risk factor for hepatocellular carcinoma. The aim of this study was to explore the characteristics of low-level viremia patients with hepatitis B-related hepatocellular carcinoma and identify prognostic factors after curative hepatectomy. Methods Data from chronic hepatitis B patients with hepatocellular carcinoma receiving curative hepatectomy for the first time in the first hospital of China Medical University were studied. Patients were divided into two groups based on preoperative HBV DNA levels: group 1 (low-level viremia group, HBV DNA < 2000 IU/mL) and group 2 (HBV DNA ≥ 2000 IU/mL). Results Of the 212 patients, 104 patients were in group 1 and 108 patients were in group 2. There was a lower proportion of patients with HBsAg levels > 250 IU/mL (the upper limit of detection in our laboratory) in group 1 than in group 2 (71.2% vs. 86.1%, P < 0.01). The percentage of patients with a tumor diameter < 5 cm was 67.3% in group 1 and 37.0% in group 2 (P < 0.000). The percentage of tumor recurrence was 40.4% (42) in group 1 and 54.6% (59) in group 2 (P < 0.05). Median recurrence-free survival was 30.1 months in group 1 and 17.6 months in group 2 (P < 0.01). Multivariate analysis showed that a tumor diameter ≥ 5 cm (hazard ratio [HR] = 1.819, 95% confidence interval [CI] 1.193–2.775, P = 0.005), intrahepatic metastasis (HR = 1.916, 95% CI 1.077–3.407, P = 0.027), and an HBV DNA level ≥ 100 IU/mL (the lower limit of detection in our laboratory, HR = 2.943, 95% CI 1.916–4.520, P < 0.000) were independent prognostic factors associated with an increased risk of hepatocellular carcinoma recurrence. Conclusion Preoperative low-level viremia was related with a long tumor recurrence interval and complete virologic response after curative hepatectomy was associated with a lower risk of hepatocellular carcinoma recurrence.
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Affiliation(s)
- Furong Sun
- Department of Elderly Gastroenterology, The First Hospital of China Medical University, Shenyang, 110001, China
| | - Zhifei Liu
- School of Pharmacy, China Medical University, Shenyang, 110001, China
| | - Bingyuan Wang
- Department of Elderly Gastroenterology, The First Hospital of China Medical University, Shenyang, 110001, China.
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Reig M, Forner A, Ávila MA, Ayuso C, Mínguez B, Varela M, Bilbao I, Bilbao JI, Burrel M, Bustamante J, Ferrer J, Gómez MÁ, Llovet JM, De la Mata M, Matilla A, Pardo F, Pastrana MA, Rodríguez-Perálvarez M, Tabernero J, Urbano J, Vera R, Sangro B, Bruix J. Diagnosis and treatment of hepatocellular carcinoma. Update of the consensus document of the AEEH, AEC, SEOM, SERAM, SERVEI, and SETH. Med Clin (Barc) 2021; 156:463.e1-463.e30. [PMID: 33461840 DOI: 10.1016/j.medcli.2020.09.022] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 09/12/2020] [Accepted: 09/15/2020] [Indexed: 12/12/2022]
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver neoplasm and one of the most common causes of death in patients with cirrhosis of the liver. In parallel, with recognition of the clinical relevance of this cancer, major new developments have recently appeared in its diagnosis, prognostic assessment and in particular, in its treatment. Therefore, the Spanish Association for the Study of the Liver (AEEH) has driven the need to update the clinical practice guidelines, once again inviting all the societies involved in the diagnosis and treatment of this disease to participate in the drafting and approval of the document: Spanish Society for Liver Transplantation (SETH), Spanish Society of Diagnostic Radiology (SERAM), Spanish Society of Vascular and Interventional Radiology (SERVEI), Spanish Association of Surgeons (AEC) and Spanish Society of Medical Oncology (SEOM). The clinical practice guidelines published in 2016 and accepted as National Health System Clinical Practice Guidelines were taken as the reference documents, incorporating the most important recent advances. The scientific evidence and the strength of the recommendation is based on the GRADE system.
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Affiliation(s)
- María Reig
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, IDIBAPS, Universidad de Barcelona, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España
| | - Alejandro Forner
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, IDIBAPS, Universidad de Barcelona, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España
| | - Matías A Ávila
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Programa de Hepatología, Centro de Investigación Médica Aplicada, Universidad de Navarra-IDISNA, Pamplona, España
| | - Carmen Ayuso
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Servicio de Radiodiagnóstico, Hospital Clínic Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Beatriz Mínguez
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Servicio de Hepatología, Hospital Universitario Vall d́Hebron, Grupo de Investigación en Enfermedades Hepáticas (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universidad Autónoma de Barcelona. Barcelona, España
| | - María Varela
- Sección de Hepatología, Servicio de Aparato Digestivo, Hospital Universitario Central de Asturias. Oviedo, España
| | - Itxarone Bilbao
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Servicio de Cirugía Hepatobiliopancreática y Trasplantes Digestivos, Hospital Universitario Vall d'Hebron, Universidad Autónoma de Barcelona. Barcelona, España
| | - José Ignacio Bilbao
- Unidad de Radiología Vascular e Intervencionista, Departamento de Radiodiagnóstico, Clínica Universidad de Navarra, Pamplona, España
| | - Marta Burrel
- Servicio de Radiodiagnóstico, Hospital Clínic Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Javier Bustamante
- Servicio de Gastroenterología y Hepatología, Sección de Hepatología y Trasplante, Hospital Universitario de Cruces, Baracaldo, España
| | - Joana Ferrer
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Cirugía Hepatobiliopancreática, Hospital Clínic, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Miguel Ángel Gómez
- Unidad de Cirugía Hepatobiliopancreática y Trasplantes, Hospital Universitario Virgen del Rocío, Sevilla, España
| | - Josep María Llovet
- Grupo de Investigación Traslacional en Oncología Hepática, Servicio de Hepatología, Hospital Clínic, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Manuel De la Mata
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Unidad Clínica de Aparato Digestivo, Hospital Universitario Reina Sofía, Córdoba, España
| | - Ana Matilla
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Sección de Hepatología, Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, Madrid, España
| | - Fernando Pardo
- Servicio de Cirugía Hepatobiliopancreática y Trasplante, Clínica Universidad de Navarra, Pamplona, España
| | - Miguel A Pastrana
- Servicio de Radiodiagnóstico, Hospital Universitario Puerta de Hierro, Universidad Autónoma de Madrid, Madrid, España
| | - Manuel Rodríguez-Perálvarez
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Unidad Clínica de Aparato Digestivo, Hospital Universitario Reina Sofía, Córdoba, España
| | - Josep Tabernero
- Servicio de Oncología Médica, Hospital Universitario Vall d'Hebron, Universidad Autónoma de Barcelona, Barcelona, España
| | - José Urbano
- Unidad de Radiología Vascular e Intervencionista, Servicio de Radiodiagnóstico, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Madrid, España
| | - Ruth Vera
- Servicio de Oncología Médica, Complejo hospitalario de Navarra, Navarrabiomed-IDISNA, Pamplona, España
| | - Bruno Sangro
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Unidad de Hepatología y Área de Oncología HBP, Clínica Universidad de Navarra-IDISNA, Pamplona, España.
| | - Jordi Bruix
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, IDIBAPS, Universidad de Barcelona, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España.
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Qian X, Liu S, Long H, Zhang S, Yan X, Yao M, Zhou J, Gong J, Wang J, Wen X, Zhou T, Zhai X, Xu Q, Zhang T, Chen X, Hu G, Wang J, Gao Z, Nan Y, Chen J, Hu B, Zhao J, Lu F. Reappraisal of the diagnostic value of alpha-fetoprotein for surveillance of HBV-related hepatocellular carcinoma in the era of antiviral therapy. J Viral Hepat 2021; 28:20-29. [PMID: 32852885 PMCID: PMC7756791 DOI: 10.1111/jvh.13388] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Revised: 07/03/2020] [Accepted: 07/30/2020] [Indexed: 12/15/2022]
Abstract
This study was designed to explore if antiviral treatment influences the performance of serum alpha-fetoprotein (AFP) for hepatocellular carcinoma (HCC) among the high-risk chronic HBV-infected patients. A total of 5936 patients who had evidence of chronic HBV infection were enrolled from four independent centres in this retrospective study, including 1721 chronic hepatitis B (CHB), 2286 liver cirrhosis (LC), 798 HCC within Milan criteria and 1131 HCC beyond Milan criteria patients. Stratified by whether they received treatment or not, the patients were further divided into antiviral and non-antiviral groups. Then, the performance of AFP for discriminating HCC was evaluated. Patients receiving antivirals had significantly lower median levels of AFP compared with the non-antiviral patients (P < .001), and there were significantly less patients with abnormal AFP levels in antiviral groups (P < .001). Antiviral therapy improved the AUROCs of AFP for discriminating HCC within Milan criteria. When setting the cut-off values at 20 ng/mL and 100 ng/mL as surveillance and confirmatory tests respectively for HCC among patients receiving antiviral treatment, AFP exhibited a significantly higher sensitivity than those of 200 ng/mL and 400 ng/mL, which are currently recommended by some guidelines, without compromising specificity. Further analysis in antiviral patients revealed that serum AFP had better performance for discriminating HCC within Milan criteria in ALT ≤ 1ULN patients than that in ALT > 1ULN patients. In conclusion, in the era of antiviral therapy, serum AFP's surveillance performance was substantially improved for HCC within Milan criteria among the high-risk population of CHB and LC patients.
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Affiliation(s)
- Xiangjun Qian
- Department of Microbiology & Infectious Disease CenterSchool of Basic Medical SciencesPeking University Health Science CenterBeijingChina
| | - Shuhong Liu
- Department of Pathology and HepatologyThe 5th Medical CentreChinese PLA General HospitalBeijingChina
| | - Huiling Long
- Department of Infectious DiseasesThird Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
| | - Siyu Zhang
- Department of Traditional and Western Medical HepatologyThe Third Hospital of Hebei Medical UniversityShijiazhuangChina
| | - Xiaotong Yan
- Department of Epidemiology and BiostatisticsCollege of Public HealthZhengzhou UniversityZhengzhouChina
| | - Mingjie Yao
- Department of Microbiology & Infectious Disease CenterSchool of Basic Medical SciencesPeking University Health Science CenterBeijingChina
| | - Jiyuan Zhou
- Intervention and Cell Therapy CenterPeking University Shenzhen HospitalShenzhenChina
| | - Jiao Gong
- Department of Laboratory MedicineThird Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
| | - Jianwen Wang
- Department of Microbiology & Infectious Disease CenterSchool of Basic Medical SciencesPeking University Health Science CenterBeijingChina
| | - Xiajie Wen
- Department of Microbiology & Infectious Disease CenterSchool of Basic Medical SciencesPeking University Health Science CenterBeijingChina
| | - Tao Zhou
- Intervention and Cell Therapy CenterPeking University Shenzhen HospitalShenzhenChina
| | - Xiangwei Zhai
- Department of Epidemiology and BiostatisticsCollege of Public HealthZhengzhou UniversityZhengzhouChina
| | - Qiang Xu
- Department of Microbiology & Infectious Disease CenterSchool of Basic Medical SciencesPeking University Health Science CenterBeijingChina
| | - Ting Zhang
- Department of Microbiology & Infectious Disease CenterSchool of Basic Medical SciencesPeking University Health Science CenterBeijingChina
| | - Xiangmei Chen
- Department of Microbiology & Infectious Disease CenterSchool of Basic Medical SciencesPeking University Health Science CenterBeijingChina
| | - Guoxin Hu
- Department of Infectious DiseasesPeking University Shenzhen HospitalShenzhenChina
| | - Jie Wang
- Department of Microbiology & Infectious Disease CenterSchool of Basic Medical SciencesPeking University Health Science CenterBeijingChina
| | - Zhiliang Gao
- Department of Infectious DiseasesThird Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
| | - Yuemin Nan
- Department of Traditional and Western Medical HepatologyThe Third Hospital of Hebei Medical UniversityShijiazhuangChina
| | - Junhui Chen
- Intervention and Cell Therapy CenterPeking University Shenzhen HospitalShenzhenChina
| | - Bo Hu
- Department of Laboratory MedicineThird Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
| | - Jingmin Zhao
- Department of Pathology and HepatologyThe 5th Medical CentreChinese PLA General HospitalBeijingChina
| | - Fengmin Lu
- Department of Microbiology & Infectious Disease CenterSchool of Basic Medical SciencesPeking University Health Science CenterBeijingChina,Department of Epidemiology and BiostatisticsCollege of Public HealthZhengzhou UniversityZhengzhouChina
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Abstract
INTRODUCTION The most common biomarker for HCC is serum alpha-fetoprotein (AFP). AFP is used for screening and diagnosing HCC, and also, it is used for predicting prognosis and monitoring the response to treatment. DISCUSSION AFP secretion is associated with poor tumor histologic grade and aggressive tumor biological behavior. The risk of dropout on the waiting list for liver transplantation and the risk of tumor recurrence after liver transplantation are associated with high AFP serum levels. Therefore, using AFP levels for selecting patients to include on the liver transplantation waiting lists is critical. It is also known that a low AFP serum level before liver transplantation has limited informative value, but high AFP levels prior to liver transplantation indicate a higher risk for HCC recurrence. CONCLUSION AFP's performance as a screening, diagnostic, and prognostic marker for HCC is not ideal, but it is the most frequently used biomarker in the management of HCC.
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Affiliation(s)
- Fatih Özdemir
- Department of Surgery, Liver Transplantation Institute, Inonu University, 44315, Malatya, Turkey.
| | - Adil Baskiran
- Department of Surgery, Liver Transplantation Institute, Inonu University, 44315, Malatya, Turkey
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Zong X, Yang JX, Zhang Y. Persistently elevated alpha-fetoprotein associated with chronic hepatitis B during chemotherapy for malignant ovarian germ cell tumors: a case series and a review of the literature. J Ovarian Res 2019; 12:124. [PMID: 31836006 PMCID: PMC6911275 DOI: 10.1186/s13048-019-0598-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Accepted: 12/04/2019] [Indexed: 12/17/2022] Open
Abstract
Background Alpha-fetoprotein (AFP) plays a crucial role in the management of malignant ovarian germ cell tumors (MOGCTs) and is an important reference index for chemotherapy termination. However, a high level of AFP can also be caused by several benign diseases, causing confusion and impacting treatment decisions. Case presentation We described four patients who were diagnosed with MOGCTs; the histologic subtype in two of them was mixed MOGCTs (yolk sac tumor with mature teratoma), while the rest was immature teratoma. The serum AFP level of each patient was abnormal before surgery, but it was still persistently elevated around 300 ng/ml even after additional cycles of chemotherapy. All patients were thoroughly evaluated, but we did not find any evidence of disease progression or residual tumors. Liver function tests were normal, whereas serum assays revealed positive of hepatitis B surface antigen, and two patients had a high level of HBV-DNA. They were chronic carriers of hepatitis B virus and never received relevant treatments. Then they were managed with tumor surveillance and the antiviral treatment. Thereafter, the AFP levels presented a slowly decreasing trend. Conclusions False elevation of AFP in MOGCTs is a rare condition and should be assessed with a comprehensive evaluation to avoid unnecessary treatments.
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Affiliation(s)
- Xuan Zong
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China
| | - Jia-Xin Yang
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.
| | - Ying Zhang
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China
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Galle PR, Foerster F, Kudo M, Chan SL, Llovet JM, Qin S, Schelman WR, Chintharlapalli S, Abada PB, Sherman M, Zhu AX. Biology and significance of alpha-fetoprotein in hepatocellular carcinoma. Liver Int 2019; 39:2214-2229. [PMID: 31436873 DOI: 10.1111/liv.14223] [Citation(s) in RCA: 353] [Impact Index Per Article: 58.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Revised: 07/19/2019] [Accepted: 08/03/2019] [Indexed: 12/11/2022]
Abstract
Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related deaths globally due, in part, to the majority of patients being diagnosed with intermediate or advanced stage disease. Our increased understanding of the heterogeneous molecular pathogenesis of HCC has led to significant developments in novel targeted therapies. Despite these advances, there remains a high unmet need for new treatment options. HCC is a complex disease with multiple pathogenic mechanisms caused by a variety of risk factors, making it difficult to characterize with a single biomarker. In fact, numerous biomarkers have been studied in HCC, but alpha-fetoprotein (AFP) remains the most widely used and accepted serum marker since its discovery over 60 years ago. This review summarizes the most relevant studies associated with the regulation of AFP at the gene and protein levels; the pathophysiology of AFP as a pro-proliferative protein; and the correlation of AFP with molecular HCC subclasses, the vascular endothelial growth factor pathway and angiogenesis. Also described are the historical and current uses of AFP for screening and surveillance, diagnosis, its utility as a prognostic and predictive biomarker and its role as a tumour antigen in HCC. Taken together, these data demonstrate the relevance of AFP for patients with HCC and identify several remaining questions that will benefit from future research.
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Affiliation(s)
- Peter R Galle
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Friedrich Foerster
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | | | | | - Josep M Llovet
- Translational Research in Hepatic Oncology, Liver Unit, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.,Mount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.,Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
| | - Shukui Qin
- Cancer Center of Bayi Hospital, Nanjing Chinese Medicine University, Nanjing, China
| | | | | | | | | | - Andrew X Zhu
- Massachusetts General Hospital Cancer Center, Harvard Medical Center, Boston, MA, USA
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11
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Loglio A, Iavarone M, Viganò M, Orenti A, Facchetti F, Cortinovis I, Lunghi G, Ceriotti F, Occhipinti V, Rumi M, Sangiovanni A, Colombo M, Lampertico P. Minimal increases of serum alpha-foetoprotein herald HCC detection in Caucasian HBV cirrhotic patients under long-term oral therapy. Liver Int 2019; 39:1964-1974. [PMID: 31323159 DOI: 10.1111/liv.14197] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2019] [Revised: 07/06/2019] [Accepted: 07/10/2019] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS In Caucasian patients with compensated cirrhosis caused by hepatitis B virus (HBV), the risk of hepatocellular carcinoma (HCC) developing persist despite long-term nucleos(t)ide analogs (NUC) treatment. In the surveillance of this population with persistently normal transaminases because of NUCs, the added value of serum alpha-foetoprotein (AFP) monitoring is poorly defined. METHODS Two hundred and fifty-eight Caucasian HCC-free patients with HBV-compensated cirrhosis who started tenofovir or entecavir while having normal serum AFP levels (≤7 ng/mL) at baseline or within the first year of treatment underwent HCC surveillance by semiannual ultrasound evaluation and serum AFP determination. RESULTS During 96 (18-120) months of antiviral therapy, 3947 AFP values were collected, median AFP level was 2 ng/mL. Thirty-five patients developed an HCC at an overall 8-year crude cumulative incidence of 14% (annual incidence of 2%). HCC incidence increased in parallel with increasing AFP thresholds: 24%, 36%, 64% and 92% for AFP levels after exceeding 2, 4, 6 and 7 ng/mL for the first-time. Of the 12 patients who experienced an AFP rise > 7 ng/mL, 11 developed an HCC and one had liver metastases of lung cancer. Overall, an AFP > 7 ng/mL had 99.6% specificity, 31.4% sensitivity, 91.7% PPV, 90.2% NPV, LR+ 70.1 and LR- 0.69 for HCC; this excellent specificity was maintained up to 18 months before HCC detection. CONCLUSIONS In Caucasian patients with HBV-compensated cirrhosis on long-term NUC, an increase in AFP over 7 ng/mL shows excellent specificity, heralding HCC development within 1 year.
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Affiliation(s)
- Alessandro Loglio
- CRC 'A. M. and A. Migliavacca' Center for the Study of Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Massimo Iavarone
- CRC 'A. M. and A. Migliavacca' Center for the Study of Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Mauro Viganò
- Division of Hepatology, Ospedale San Giuseppe, Università degli Studi di Milano, Milan, Italy
| | - Annalisa Orenti
- Department of Clinical Sciences and Community Health, Laboratory of Statistics, Epidemiology and Biometry 'G.A. Maccacaro', Università degli Studi di Milano, Milan, Italy
| | - Floriana Facchetti
- CRC 'A. M. and A. Migliavacca' Center for the Study of Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Ivan Cortinovis
- Department of Clinical Sciences and Community Health, Laboratory of Statistics, Epidemiology and Biometry 'G.A. Maccacaro', Università degli Studi di Milano, Milan, Italy
| | - Giovanna Lunghi
- Virology Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Ferruccio Ceriotti
- Virology Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Vincenzo Occhipinti
- Division of Hepatology, Ospedale San Giuseppe, Università degli Studi di Milano, Milan, Italy
| | - Mariagrazia Rumi
- Division of Hepatology, Ospedale San Giuseppe, Università degli Studi di Milano, Milan, Italy
| | - Angelo Sangiovanni
- CRC 'A. M. and A. Migliavacca' Center for the Study of Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Massimo Colombo
- Center for Translational Hepatology Research, Clinical and Research Center Humanitas Hospital, Rozzano, Italy
| | - Pietro Lampertico
- CRC 'A. M. and A. Migliavacca' Center for the Study of Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
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12
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Fouad R, Elsharkawy A, Abdel Alem S, El Kassas M, Alboraie M, Sweedy A, Afify S, Abdellatif Z, Khairy M, Esmat G. Clinical impact of serum α-fetoprotein and its relation on changes in liver fibrosis in hepatitis C virus patients receiving direct-acting antivirals. Eur J Gastroenterol Hepatol 2019; 31:1129-1134. [PMID: 30896550 DOI: 10.1097/meg.0000000000001400] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND α-Fetoprotein (AFP) is used widely as a serological marker for hepatocellular carcinoma. However, the AFP value is elevated in chronic hepatitis C virus (HCV) patients without hepatocellular carcinoma. Yet, data on the impact of direct-acting antiviral agents (DAAs) therapy on AFP levels after viral eradication are still lacking. AIM The aim of this study was to elucidate the changes in the serum AFP level in chronic hepatitis C patients treated with DAA-based therapy and their relation to response and liver fibrosis parameters. PATIENTS AND METHODS A total of 456 chronic HCV patients who received different DAAs-based treatment regimens were enrolled. Laboratory data including serum AFP, transient elastography values, and fibrosis scores were recorded at baseline and sustained virological response at 24 weeks after treatment (SVR24). The outcome was the changes in the AFP level from baseline to SVR24 and its relation to changes in liver fibrosis parameters at SVR24 using Spearman's rank correlation test. RESULTS Overall, 96.9% of enrolled patients were responders. A statistically significant improvement in serum transaminases, albumin, transient elastography values, and fibrosis scores at SVR24 was reported. The AFP level was significantly decreased from a median (interquartile range) of 6 (3.2-10.8) ng/ml before DAAs to 4 (2.3-6) ng/ml at SVR24 (P < 0.0001). Only 22.6% of patients showed an increase in the AFP level after treatment. On multivariate analysis, the only independent baseline variable associated with an increase in the AFP level after treatment was baseline AFP (odds ratio: 0.95, 95% confidence interval: 0.91-0.99, P = 0.02). There is a significant correlation between changes in AFP and liver fibrosis parameters at SVR24. CONCLUSION DAAs-based regimens are a highly efficient antiviral therapy for chronic hepatitis C patients that resulted in improvements in the serum AFP level.
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Affiliation(s)
- Rabab Fouad
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University
| | - Aisha Elsharkawy
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University
| | - Shereen Abdel Alem
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University
| | - Mohamed El Kassas
- Department of Endemic Medicine, Faculty of Medicine, Helwan University
| | | | | | - Shimaa Afify
- Department of Tropical Medicine, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Zeinab Abdellatif
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University
| | - Marwa Khairy
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University
| | - Gamal Esmat
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University
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Campion D, Tucci A, Ponzo P, Caviglia GP. Non-invasive biomarkers for the detection of hepatocellular carcinoma. MINERVA BIOTECNOL 2019; 31. [DOI: 10.23736/s1120-4826.18.02488-6] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/17/2025]
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14
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Loglio A, Iavarone M, Grossi G, Viganò M, Rumi MG, Facchetti F, Lunghi G, Sangiovanni A, Colombo M, Lampertico P. Clinical features and outcomes of hepatocellular carcinoma in Caucasian cirrhotic patients on long-term analogue therapy for hepatitis B. Aliment Pharmacol Ther 2018; 48:431-439. [PMID: 29920698 DOI: 10.1111/apt.14848] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2018] [Revised: 03/02/2018] [Accepted: 05/23/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND Long-term oral nucleos(t)ide analogue (NUC) therapy in hepatitis B virus (HBV)-related compensated cirrhotics prevents clinical decompensation but not hepatocellular carcinoma (HCC) development. AIMS To define the clinical features and outcomes of HCC in long-term NUC-treated HBV patients. METHODS All HCCs developing between 2005 and 2016 in NUC-treated HBV patients under surveillance were studied, excluding those that occurred within the first 6 months of therapy. Clinical features of HCC, alpha faetoprotein (AFP) patterns and patients' outcome were studied. RESULTS Seventy-six HCC patients were included. Median age was 67 (40-83) years, 84% males, 96% Caucasian, 95% HBeAg-negative, 96% with undetectable HBV DNA, 83% with normal ALT levels, and 92% with compensated cirrhosis. Median serum AFP levels were 4 (1-3615) ng/mL (>7 ng/mL in 36%). HCC was monofocal in 78%, had a median diameter of 20 (6-57) mm and was in its early stage in 92% which allowed potentially curative treatments in 78% (39% ablation, 28% surgical resection, 11% liver transplantation). Overall, a complete response was obtained in 61 (80%) patients: in 40 after a first-line treatment, in 3 after the second-line treatment, in 2 after the third-line treatment, while 16 underwent liver transplantation (8 as second line). During 45 (7-144) months after HCC diagnosis, 19 patients died, 84% from HCC progression. The median time to recurrence was 20.2 (3-53) months, and the cumulative 5-year liver-related survival was 74%. CONCLUSIONS HCCs developing in patients under long-term NUC treatment were single, small tumours, amenable to curative therapies able to confer excellent 5-year survival rates.
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Affiliation(s)
- A Loglio
- CRC "A.M. e A. Migliavacca" Center for the Study of Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - M Iavarone
- CRC "A.M. e A. Migliavacca" Center for the Study of Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - G Grossi
- CRC "A.M. e A. Migliavacca" Center for the Study of Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - M Viganò
- Hepatology Division, Ospedale San Giuseppe, Università degli Studi di Milano, Milan, Italy
| | - M G Rumi
- Hepatology Division, Ospedale San Giuseppe, Università degli Studi di Milano, Milan, Italy
| | - F Facchetti
- CRC "A.M. e A. Migliavacca" Center for the Study of Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - G Lunghi
- Virology Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - A Sangiovanni
- CRC "A.M. e A. Migliavacca" Center for the Study of Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - M Colombo
- Center for Translational Hepatology Research, Clinical and Research Center, Humanitas Hospital, Rozzano, Italy
| | - P Lampertico
- CRC "A.M. e A. Migliavacca" Center for the Study of Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
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15
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Galle PR, Forner A, Llovet JM, Mazzaferro V, Piscaglia F, Raoul JL, Schirmacher P, Vilgrain V. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol 2018; 69:182-236. [PMID: 29628281 DOI: 10.1016/j.jhep.2018.03.019] [Citation(s) in RCA: 5888] [Impact Index Per Article: 841.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Accepted: 03/20/2018] [Indexed: 02/06/2023]
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16
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A Nodule, is a Nodule, is a Nodule: May Alpha-Fetoprotein Make the Difference? Am J Gastroenterol 2017; 112:1340. [PMID: 28766576 DOI: 10.1038/ajg.2017.128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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17
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Nguyen K, Jimenez M, Moghadam N, Wu C, Farid A, Grotts J, Elashoff D, Choi G, Durazo FA, El-Kabany MM, Han SHB, Saab S. Decrease of Alpha-fetoprotein in Patients with Cirrhosis Treated with Direct-acting Antivirals. J Clin Transl Hepatol 2017; 5:43-49. [PMID: 28507926 PMCID: PMC5411356 DOI: 10.14218/jcth.2016.00057] [Citation(s) in RCA: 12] [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: 11/03/2016] [Revised: 01/26/2017] [Accepted: 02/01/2017] [Indexed: 12/11/2022] Open
Abstract
Background and Aims: The lack of specificity has limited the role of serum alpha-fetoprotein (AFP) for hepatocellular carcinoma (HCC) screening among patients with cirrhosis related to hepatitis C virus (HCV) infection. We sought to examine whether AFP may decrease after achieving a sustained virological response (SVR) in patients with HCV-related cirrhosis. Methods: We performed a retrospective study of patients with HCV-related cirrhosis who were cured with direct-acting antiviral (DAA) therapy at the University of California, Los Angeles. Laboratory values, including serum AFP, were measured before and after completing the DAA treatment. Results: Fifty-six patients met the inclusion criteria, with median (interquartile range [IQR]) age of 67 (58-69) years and with 51.8% being male. All patients received DAA therapy without interferon. AFP decreased from median (IQR) 7.2 (4.2-13.4) ng/mL before DAAs to 4.2 (2.7-6.3) ng/mL at the end of treatment and 4.2 (2.9-6.8) ng/mL at 12 weeks after treatment (p < 0.001). Model for end-stage liver disease (MELD), fibrosis-4 (FIB4), and aspartate transaminase (AST) to platelet ratio index (APRI) scores at baseline were not significantly associated with AFP reduction. On multivariate analysis, platelet count, AST and total bilirubin at baseline were significantly correlated to AFP reduction (p = 0.04, 0.009 and 0.04, respectively). The higher the baseline AFP, the greater the reduction in AFP. There was no statistically significant correlation between baseline AFP and MELD, FIB4 or APRI scores. Conclusion: There was a significant decrease in AFP in patients with cirrhosis who achieved a SVR with DAAs. Given a reduction in AFP after DAA treatment, AFP should be further studied as a screening modality for HCC in patients with cirrhosis.
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Affiliation(s)
- Kelvin Nguyen
- Departments of Medicine, the University of California at Los Angeles, Los Angeles, CA, USA
| | - Melissa Jimenez
- Departments of Surgery, the University of California at Los Angeles, Los Angeles, CA, USA
| | - Nima Moghadam
- Departments of Surgery, the University of California at Los Angeles, Los Angeles, CA, USA
| | - Crystal Wu
- Departments of Surgery, the University of California at Los Angeles, Los Angeles, CA, USA
| | - Alex Farid
- Departments of Surgery, the University of California at Los Angeles, Los Angeles, CA, USA
| | - Jonathan Grotts
- Departments of Medicine, the University of California at Los Angeles, Los Angeles, CA, USA
| | - David Elashoff
- Departments of Medicine, the University of California at Los Angeles, Los Angeles, CA, USA
- Departments of Biostatistics, the University of California at Los Angeles, Los Angeles, CA, USA
| | - Gina Choi
- Departments of Medicine, the University of California at Los Angeles, Los Angeles, CA, USA
- Departments of Surgery, the University of California at Los Angeles, Los Angeles, CA, USA
| | - Francisco A. Durazo
- Departments of Medicine, the University of California at Los Angeles, Los Angeles, CA, USA
- Departments of Surgery, the University of California at Los Angeles, Los Angeles, CA, USA
| | - Mohamed M. El-Kabany
- Departments of Medicine, the University of California at Los Angeles, Los Angeles, CA, USA
- Departments of Surgery, the University of California at Los Angeles, Los Angeles, CA, USA
| | - Steven-Huy B. Han
- Departments of Medicine, the University of California at Los Angeles, Los Angeles, CA, USA
- Departments of Surgery, the University of California at Los Angeles, Los Angeles, CA, USA
| | - Sammy Saab
- Departments of Medicine, the University of California at Los Angeles, Los Angeles, CA, USA
- Departments of Surgery, the University of California at Los Angeles, Los Angeles, CA, USA
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18
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Kim CY, Kim BR, Lee SS, Jeon DH, Lee CM, Kim WS, Cho HC, Kim JJ, Lee JM, Kim HJ, Ha CY, Kim HJ, Kim TH, Jung WT, Lee OJ. Clinical features of hepatitis B and C virus infections, with high α-fetoprotein levels but not hepatocellular carcinoma. Medicine (Baltimore) 2017; 96:e5844. [PMID: 28079817 PMCID: PMC5266179 DOI: 10.1097/md.0000000000005844] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
The appropriate α-fetoprotein (AFP) level to confirm hepatocellular carcinoma (HCC) could be 100 ng/mL; however, the clinical significance of falsely elevated AFP in patients without HCC has not been fully studied. We investigated the clinical features and outcome of patients without HCC but with high AFP levels (100 ng/mL), especially with chronic hepatitis B (CHB) or C (CHC).The sample included 124 consecutive patients with CHB (n = 97) or CHC (n = 27), with AFP levels >100 ng/mL and without HCC at baseline. Multivariate Cox proportional regression analysis was performed to determine the factors associated with AFP normalization and HCC development.During the mean 52-month follow-up, the proportion of patients with CHB with AFP normalization (90.7%) was significantly higher than the proportion of patients with CHC (59.3%, P < 0.001). Initial aspartate aminotransferase levels (hazard ratio [HR] = 1.02 per 10 U/L increase, P = 0.021) and antiviral therapy (HR = 2.89, P < 0.001) were significantly associated with AFP normalization. Of the 16 (12.9%) patients who developed HCC, hepatitis B virus infection (HR = 10.82, P = 0.001), initiation of antiviral treatment postenrollment (HR = 0.23, P = 0.030), and AFP normalization within 12 months (HR = 0.13, P = 0.011) were associated with HCC development.CHB and CHC were the most common causes of falsely elevated AFP (>100 ng/mL). With either CHB or CHC, persistent AFP elevation (>12 months), regardless of antiviral treatment, might be an important marker of HCC development.
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Affiliation(s)
- Cha Young Kim
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju
| | - Bo Ra Kim
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju
| | - Sang Soo Lee
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju
- Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Changwon
| | - Dae-Hong Jeon
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju
| | - Chang Min Lee
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju
| | - Wan Soo Kim
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju
- Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Changwon
| | - Hyun Chin Cho
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju
| | - Jin Joo Kim
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju
- Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Changwon
| | - Jae Min Lee
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju
- Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Changwon
| | - Hong Jun Kim
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju
| | - Chang Yoon Ha
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju
| | - Hyun Jin Kim
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju
- Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Changwon
- Institute of Health Sciences, Gyeongsang National University, Jinju, Republic of Korea
| | - Tae Hyo Kim
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju
- Institute of Health Sciences, Gyeongsang National University, Jinju, Republic of Korea
| | - Woon Tae Jung
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju
- Institute of Health Sciences, Gyeongsang National University, Jinju, Republic of Korea
| | - Ok-Jae Lee
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju
- Institute of Health Sciences, Gyeongsang National University, Jinju, Republic of Korea
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Optimizing Surveillance Performance of Alpha-Fetoprotein by Selection of Proper Target Population in Chronic Hepatitis B. PLoS One 2016; 11:e0168189. [PMID: 27997559 PMCID: PMC5172583 DOI: 10.1371/journal.pone.0168189] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2016] [Accepted: 11/29/2016] [Indexed: 12/21/2022] Open
Abstract
Although alpha-fetoprotein (AFP) is the most widely used biomarker in hepatocellular carcinoma (HCC) surveillance, disease activity may also increase AFP levels in chronic hepatitis B (CHB). Since nucleos(t)ide analog (NA) therapy may reduce not only HBV viral loads and transaminase levels but also the falsely elevated AFP levels in CHB, we tried to determine whether exposure to NA therapy influences AFP performance and whether selective application can optimize the performance of AFP testing in CHB during HCC surveillance. A retrospective cohort of 6,453 CHB patients who received HCC surveillance was constructed from the electronic clinical data warehouse. Covariates of AFP elevation were determined from 53,137 AFP measurements, and covariate-specific receiver operating characteristics regression analysis revealed that albumin levels and exposure to NA therapy were independent determinants of AFP performance. C statistics were largest in patients with albumin levels ≥ 3.7 g/dL who were followed without NA therapy during study period, whereas AFP performance was poorest when tested in patients with NA therapy during study and albumin levels were < 3.7 g/dL (difference in C statics = 0.35, p < 0.0001). Contrary to expectation, CHB patients with current or recent exposure to NA therapy showed poorer performance of AFP during HCC surveillance. Combination of concomitant albumin levels and status of NA therapy can identify subgroup of CHB patients who will show optimized AFP performance.
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Varbobitis I, Papatheodoridis GV. The assessment of hepatocellular carcinoma risk in patients with chronic hepatitis B under antiviral therapy. Clin Mol Hepatol 2016; 22:319-326. [PMID: 27729632 PMCID: PMC5066383 DOI: 10.3350/cmh.2016.0045] [Citation(s) in RCA: 68] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2016] [Revised: 07/21/2016] [Accepted: 08/11/2016] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a primary concern for patients with chronic hepatitis B (CHB). Antiviral therapy has been reasonably the focus of interest for HCC prevention, with most studies reporting on the role of the chronologically preceding agents, interferon-alfa and lamivudine. The impact of interferon-alfa on the incidence of HCC is clearer in Asian patients and those with compensated cirrhosis, as several meta-analyses have consistently shown HCC risk reduction, compared to untreated patients. Nucleos(t)ide analogues also seem to have a favorable impact on the HCC incidence when data from randomized or matched controlled studies are considered. Given that the high-genetic barrier agents, entecavir and tenofovir, are mainly used in CHB because of their favorable effects on the overall long-term outcome of such patients, the most clinically important challenge is the identification of patients who require close HCC surveillance despite on-therapy virological remission. Several risk scores have been developed for HCC prediction in CHB patients. Most of them, such as GAG-HCC, CU-HCC and REACH-B, have been developed and validated in Asian untreated and treated CHB patients, but they do not seem to offer good predictability in Caucasian CHB patients for whom a newer score, PAGE-B, has been recently developed.
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Affiliation(s)
- Ioannis Varbobitis
- Academic Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
| | - George V. Papatheodoridis
- Academic Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
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Jang ES, Jeong SH, Kim JW, Choi YS, Leissner P, Brechot C. Diagnostic Performance of Alpha-Fetoprotein, Protein Induced by Vitamin K Absence, Osteopontin, Dickkopf-1 and Its Combinations for Hepatocellular Carcinoma. PLoS One 2016; 11:e0151069. [PMID: 26986465 PMCID: PMC4795737 DOI: 10.1371/journal.pone.0151069] [Citation(s) in RCA: 72] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2015] [Accepted: 02/23/2016] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND & AIMS Alpha-fetoprotein (AFP) is the most widely used serum biomarker for hepatocellular carcinoma (HCC), despite its limitations. As complementary biomarkers, protein induced by vitamin K absence (PIVKA-II), osteopontin (OPN), and Dickkopf-1 (DKK-1) have been proposed. This study aimed to perform a head-to-head comparison of the diagnostic performance of AFP, PIVKA-II, OPN and DKK-1 as single or in combination to seek the best biomarker or panel, and to investigate the clinical factors affecting their performance. METHODS Using 401 stored plasma samples obtained from 208 HCC patients and 193 liver cirrhosis control patients, plasma AFP, PIVKA-II, OPN and DKK-1 levels were measured by ELISA, and receiver operating characteristic curve analyses were performed for each biomarker and for every combination of two to four markers. RESULTS Of the four biomarkers, AFP showed the highest area under the curve (0.786). The sensitivity and specificity for each single biomarker was 62% and 90.2% (AFP>20 ng/mL), 51.0% and 91.2% (PIVKA-II>10 ng/mL), 46.2% and 80.3% (OPN>100 ng/mL), and 50.0% and 80.8% (DKK-1>500 pg/mL), respectively. Among the combinations of two biomarkers, AFP>20 ng/mL or DKK-1>500 pg/mL showed the best diagnostic performance (sensitivity 78.4%, specificity 72.5%). Triple or quadruple combination did not improve the diagnostic performance further. The patient's age, etiology and tumor invasiveness of HCC affected the performance of each marker. CONCLUSIONS AFP was the most useful single biomarker for HCC diagnosis, and the combined measurement of AFP and DKK-1 could maximize the diagnostic yield. Clinical decision should be based on the consideration of various factors affecting the diagnostic performance of each biomarker. Efforts to seek novel HCC biomarkers should be continued.
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Affiliation(s)
- Eun Sun Jang
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seoul, Republic of Korea
| | - Sook-Hyang Jeong
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seoul, Republic of Korea
| | - Jin-Wook Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seoul, Republic of Korea
| | - Yun Suk Choi
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seoul, Republic of Korea
| | - Philippe Leissner
- Medical Diagnostics Discovery Department, bioMérieux, Marcy l’Etoile, France
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Fahrner R, Dondorf F, Ardelt M, Dittmar Y, Settmacher U, Rauchfuß F. Liver transplantation for hepatocellular carcinoma - factors influencing outcome and disease-free survival. World J Gastroenterol 2015; 21:12071-12082. [PMID: 26576092 PMCID: PMC4641125 DOI: 10.3748/wjg.v21.i42.12071] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 08/04/2015] [Accepted: 09/14/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma is one of the leading causes of cancer-related death worldwide. Liver transplantation can be a curative treatment in selected patients. However, there are several factors that influence disease-free survival after transplantation. This review addresses the pre-, intra- and postoperative factors that influence the risk of tumor recurrence after liver transplantation.
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Yang SW, Kim GH, Chung JW, Sohn HR, Lee SS, Hong S, Chung SM, Jang ES, Jeong SH, Kim JW. Prediction of risk for hepatocellular carcinoma by response of serum α-fetoprotein to entecavir therapy. J Gastroenterol Hepatol 2015; 30:1175-82. [PMID: 25707935 DOI: 10.1111/jgh.12921] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/21/2015] [Indexed: 12/31/2022]
Abstract
BACKGROUND AND AIMS Serum α-fetoprotein (AFP) is frequently elevated in patients with chronic hepatitis B (CHB) who do not have hepatocellular carcinoma (HCC). Entecavir (ETV) treatment reduces AFP levels in these patients, but the clinical significance of AFP response to ETV has not been fully studied. The aims of this study were to elucidate the temporal response of AFP to ETV therapy and to determine the relationship between AFP response and the subsequent development of HCC. METHODS All consecutive nucleos(t)ide-naïve CHB patients who started ETV therapy between March 2007 and February 2009 were selected from an electronic medical record database at a tertiary referral center (BESTCare). Clinical, biochemical, and virologic parameters were evaluated in relation to the serial AFP levels tested during ETV treatment. RESULTS Among the 244 enrolled patients, 66 had elevated AFP levels before ETV therapy. Low serum albumin was a significant predictor for elevated AFP. During 12 months of ETV therapy, AFP levels normalized in approximately three fourths of these patients. The decrease in AFP was delayed in patients with high baseline hepatitis B virus titers and in patients who subsequently developed HCC during ETV therapy. Incidence of HCC was similar regardless of baseline AFP levels. Among patients with elevated AFP, however, HCC developed exclusively in the subgroup where elevated AFP persisted for more than 6 months of ETV therapy. CONCLUSIONS Delayed AFP response to ETV may serve as an indicator of high HCC risk.
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Affiliation(s)
- Sung Wook Yang
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam-si, South Korea
| | - Gi Hyun Kim
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam-si, South Korea
| | - Jung Wha Chung
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam-si, South Korea
| | - Hyung Rae Sohn
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam-si, South Korea
| | - Sang Soo Lee
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam-si, South Korea
| | - Sukho Hong
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam-si, South Korea
| | - Seong Min Chung
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam-si, South Korea
| | - Eun Sun Jang
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam-si, South Korea.,Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea
| | - Sook-Hyang Jeong
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam-si, South Korea.,Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea
| | - Jin-Wook Kim
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam-si, South Korea.,Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea
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