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HLA-DQB1/ DRB1 Alleles Associate with Traditional Chinese Medicine Syndrome of Chronic Hepatitis B: A Potential Predictor of Progression. BIOMED RESEARCH INTERNATIONAL 2019; 2019:8146937. [PMID: 31871943 PMCID: PMC6906876 DOI: 10.1155/2019/8146937] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Revised: 10/11/2019] [Accepted: 10/26/2019] [Indexed: 12/28/2022]
Abstract
Background and Aims Traditional Chinese medicine (TCM) has been widely applied in chronic hepatitis B (CHB) supplementary treatment in China. Kidney yang deficiency syndrome (KYDS), one of the most common TCM syndromes of CHB, is more likely to progress to liver cirrhosis or hepatocellular carcinoma than other syndromes. Polymorphisms in the human leucocyte antigen- (HLA-) DQB1 and -DRB1 genes were reported to be associated with hepatitis B virus infection outcomes. Here, we investigated whether HLA-DQB1 and HLA-DRB1 are associated with the classification of CHB TCM syndromes. Methods We genotyped HLA-DQB1 and HLA-DRB1 alleles in a total of 105 subjects, including 74 CHB patients (28 KYDS and 46 non-KYDS) and 31 healthy individuals from Sichuan Province of Southwest China, by polymerase chain reaction sequence-based typing (PCR-SBT). Moreover, a meta-analysis was carried out for further verification. Results The proportion of patients with high HBV DNA load (≥2000 IU/ml) in the KYDS group is higher than that in the non-KYDS group (60.70% [17/28] vs. 28.30% [13/46]); P=0.01). The frequencies of HLA-DQB1∗02:01 (P=0.04) and HLA-DRB1∗03:01 (P=0.04) in the KYDS group were significantly increased compared to the non-KYDS group. The gene test and meta-analysis showed that HLA-DRB1∗08:03 confers susceptibility to CHB (odds ratio = 1.57). Conclusion We found an association between HLA-DRB1/DQB1 polymorphisms and KYDS of CHB. Moreover, KYDS patients of CHB are characteristic with high HBV DNA loads. These findings help to reveal the biological mechanism of KYDS in high risk of CHB progression and suggest a potential prognostic value for disease outcome evaluation.
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Ma LN, Liu XY, Lu ZH, Wu LG, Tang YY, Luo X, Hu YC, Yan TT, Wang Q, Ding XC, Xie Y. Assessment of high-sensitivity C-reactive protein tests for the diagnosis of hepatocellular carcinoma in patients with hepatitis B-associated liver cirrhosis. Oncol Lett 2017; 13:3457-3464. [PMID: 28521452 PMCID: PMC5431324 DOI: 10.3892/ol.2017.5890] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2015] [Accepted: 02/27/2017] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a common malignant tumor worldwide, with high morbidity and mortality. Chronic infection with hepatitis B virus (HBV) is a major risk factor for the development of hepatocellular carcinoma and the majority (~80%) of hepatocellular carcinoma patients in China exhibit co-morbidity with HBV-associated liver cirrhosis. The goal of reliable early diagnostic and prognostic techniques for HBV-associated HCC remains unrealized. The aim of the present study was to explore the efficacy of serum high-sensitivity C-reactive protein (hs-CRP) tests in the early diagnosis of HCC in patients with HBV-associated liver cirrhosis. A cohort of 493 patients with HBV-associated liver disease was divided into three groups: Chronic HBV (CHB) group; liver cirrhosis without HCC (LC) group; and liver cirrhosis with HCC (HCC) group. A further 47 healthy individuals comprised the healthy control (CN) group. Comparative analyses of clinical symptoms, histopathology, ultrasound imagery, computed tomography, magnetic resonance imaging, biochemistry [α-fetoprotein (AFP) and liver function enzymes], and hs-CRP tests were conducted across these four groups. Immunohistochemical analysis showed that CRP is strongly expressed in HCC tumor tissue, but is not expressed elsewhere. Analyses of the correlations between serum hs-CRP levels and HCC clinical parameters indicated that there was no correlation between serum hs-CRP levels, tumor Edmondson grade, tumor-node-metastasis stage and AFP status. Serum hs-CRP and AFP levels were found to be significantly elevated in the HCC group compared to those in the LC, CHB and CN groups (P<0.01). Receiver operator characteristic analysis showed that measurement of serum hs-CRP could differentiate HCC from HBV-associated liver cirrhosis, as well as increase the accuracy of HCC diagnoses. Additionally, measurement of hs-CRP and AFP together improved diagnostic accuracy for HCC compared with either test alone. Serum hs-CRP could have potential as an effective diagnostic tool to complement AFP in diagnosing HCC and improving the identification of AFP-negative HCC in patients with HBV-associated liver cirrhosis. The present findings may facilitate the earlier diagnosis of hepatocellular carcinoma, permitting more effective treatment and a broader spectrum of treatment modalities for patients with advanced hepatic disease.
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Affiliation(s)
- Li-Na Ma
- Department of Infectious Disease, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China
| | - Xiao-Yan Liu
- Department of Infectious Disease, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China
| | - Zhen-Hui Lu
- Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China
| | - Li-Gang Wu
- Department of Oncological Surgery, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China
| | - Yuan-Yuan Tang
- Department of Infectious Disease, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China
| | - Xia Luo
- Department of Infectious Disease, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China
| | - Yan-Chao Hu
- Department of Infectious Disease, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China
| | - Ting-Ting Yan
- Clinical Medical College, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China
| | - Qi Wang
- Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China
| | - Xiang-Chun Ding
- Department of Infectious Disease, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China
| | - Yan Xie
- Tissue Organ Bank & Tissue Engineering Centre, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.,Tissue Repair and Regeneration Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland QLD 4059, Australia
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3
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Zhu Z, Liu Z, Liu Y, Wang C, Li R, Liu H, Gu B, Li G, Zhang S. Screening and identification of the tumor-associated antigen CK10, a novel potential liver cancer marker. FEBS Open Bio 2017; 7:627-635. [PMID: 28469975 PMCID: PMC5407893 DOI: 10.1002/2211-5463.12122] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2015] [Revised: 07/08/2016] [Accepted: 08/13/2016] [Indexed: 01/26/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a malignancy that is associated with high mortality rates in Asia. These tumors are highly invasive and their etiology is frequently unknown. Thus, most patients are diagnosed in the middle and late stages of the disease, and thus do not have sufficient time for therapy. Therefore, it is essential to study the early diagnosis and treatment of HCC; in this regard, the study of tumor‐associated antigens has received much attention. Here, antigens from the human primary HCC cell line, QGY‐7703, were used to immunize mice in order to prepare monoclonal antibodies. The specific antigen recognized by antibody 11C3 was purified from total protein lysates of QGY‐7703 by immunoaffinity chromatography. The validity of the candidate antigen as a new HCC‐associated marker was tested using SDS/PAGE, western blot, HPLC‐ESI‐MS/MS, and RT‐qPCR. Our results showed that the levels of CK10 in HCC‐derived cell lines were significantly higher than those in normal liver cells. Thus, we suggest that CK10 may be involved in the formation and development of HCC, and may be a therapeutically targetable tumor‐associated antigen.
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Affiliation(s)
- Zhaoyu Zhu
- School of Life Sciences Zhengzhou University China.,Xinyang Vocational and Technical College Xinyang China
| | - Zheng Liu
- School of Life Sciences Zhengzhou University China
| | - Yuchun Liu
- School of Life Sciences Zhengzhou University China
| | - Chunyan Wang
- School of Life Sciences Zhengzhou University China
| | - Ruyu Li
- School of Life Sciences Zhengzhou University China
| | - Hui Liu
- School of Life Sciences Zhengzhou University China
| | - Baohua Gu
- School of Life Sciences Zhengzhou University China
| | - Guodong Li
- Henan Key Laboratory of Bioactive Molecules Zhengzhou University China
| | - Shoutao Zhang
- School of Life Sciences Zhengzhou University China.,Collaborative Innovation Center of New Drug Research and Safety Evaluation Zhengzhou China
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Chandra S, Kusum A, Chandra H, Yadav K, Verma SK. Familial Hepatocellular Carcinoma- First Reported Case from India. J Clin Diagn Res 2016; 10:ED11-2. [PMID: 27134884 DOI: 10.7860/jcdr/2016/17746.7427] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2015] [Accepted: 01/14/2016] [Indexed: 11/24/2022]
Abstract
Familial clustering of Hepatocellular Carcinoma (HCC) is commonly observed in various parts of the world including China and Eastern Asia where HBV is endemic while in western world, genetic factors and metabolic disorders may play an important role. In India, HCC is considered to be a rare tumour and till date no case of familial HCC has been reported here. Therefore the present case demonstrates rare occurrence of familial HCC which is being reported for the first time from India on cytology. The case also highlights an unusual feature that it was not associated with any risk factor including HBV, HCV infection, alcoholism, obesity, diabetes or smoking suggesting its independent association with genetic factors. Cytology is uncomplicated diagnostic tool for HCC and may be useful for its early diagnosis. This case also highlights the importance of early surveillance and follow up of blood relatives for every case of HCC so that early diagnosis and management of familial HCC is possible.
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Affiliation(s)
- Smita Chandra
- Associate Professor, Department of Pathology, Himalayan Institute of Medical Sciences , SRHU, Swami Ram Nagar, Doiwala, Dehradun, Uttarakhand, India
| | - Anuradha Kusum
- Professor, Department of Pathology, Himalayan Institute of Medical Sciences , SRHU, Swami Ram Nagar, Doiwala, Dehradun, Uttarakhand, India
| | - Harish Chandra
- Professor, Department of Pathology, Himalayan Institute of Medical Sciences , SRHU, Swami Ram Nagar, Doiwala, Dehradun, Uttarakhand, India
| | - Kanika Yadav
- Resident, Department of Pathology, Himalayan Institute of Medical Sciences , SRHU, Swami Ram Nagar, Doiwala, Dehradun, Uttarakhand, India
| | - Sanjiv Kumar Verma
- Professor, Department of Medicine, Himalayan Institute of Medical Sciences , SRHU, Swami Ram Nagar, Doiwala, Dehradun, Uttarakhand, India
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5
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Liu XY, Ma LN, Yan TT, Lu ZH, Tang YY, Luo X, Ding XC. Combined detection of liver stiffness and C-reactive protein in patients with hepatitis B virus-related liver cirrhosis, with and without hepatocellular carcinoma. Mol Clin Oncol 2016; 4:587-590. [PMID: 27073669 DOI: 10.3892/mco.2016.742] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2015] [Accepted: 09/07/2015] [Indexed: 02/07/2023] Open
Abstract
The aim of the present study was to investigate the usefulness of combined detection of liver stiffness (LS) and serum C-reactive protein (CRP) level in patients with hepatitis B virus (HBV)-related liver cirrhosis (LC). A total of 156 cases of previously untreated patients with HBV-related LC were classified into the LC group [LC without hepatocellular carcinoma (HCC)] and the HCC group (LC with HCC). Comparative analyses of LS and serum CRP level were conducted between these two groups. LS values and serum CRP levels were found to be significantly higher in the HCC group compared with those in the LC group (P<0.01). The LS values and serum CRP levels were not significantly different between α-fetoprotein (AFP)-positive and -negative patients. A high LS value was a high-risk factor for HCC in patients with chronic hepatitis B. The CRP-positive rate was significantly higher in the HCC group compared with that in LC group in a subset of patients with high LS values (P<0.01). In conclusion, the combined detection of LS and serum CRP may complement the measurement of AFP in the diagnosis of HBV-related HCC, improve the identification of patients with AFP-negative HCC and help distinguish HCC from LC.
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Affiliation(s)
- Xiao-Yan Liu
- Department of Infectious Diseases, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China
| | - Li-Na Ma
- Department of Infectious Diseases, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China
| | - Ting-Ting Yan
- Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China
| | - Zhen-Hui Lu
- Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China
| | - Yuan-Yuan Tang
- Department of Infectious Diseases, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China
| | - Xia Luo
- Department of Infectious Diseases, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China
| | - Xiang-Chun Ding
- Department of Infectious Diseases, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China
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6
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Zhang Z, Zhang L, Dai Y, Jin L, Sun B, Su Q, Li X. Occult hepatitis B virus infection among people with a family history of chronic hepatitis B virus infection. J Med Virol 2015; 87:1890-1898. [PMID: 25964194 DOI: 10.1002/jmv.24245] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/20/2015] [Indexed: 12/14/2022]
Abstract
UNLABELLED The prevalence of occult hepatitis B virus infection (OBI) among people with a family history of chronic hepatitis B virus (HBV) infection is unclear. Serum samples were collected from 747 hepatitis B surface antigen (HBsAg)-negative people with a family history of HBV infection and 579 HBsAg-negative volunteer blood donors. The presence of HBV DNA was evaluated using nested PCR with primers specific for the X, S, and C regions of HBV. The Pre-S1/Pre-S2/ S region PCR products for the OBI group and their family members with chronic HBV infection (control group) were sequenced and compared. The prevalence of OBI was 8.0% (60/747) among HBsAg-negative people with a family history of chronic HBV infection, compared to 2.6% (15/579) among the blood donors (P < 0.05). The prevalence of HBV genotype B infection was lower in the OBI group than in the control group (P = 0.031). The substitution rates in the major hydrophilic region and the "a" determinant seemed to be higher in the OBI group (0.893 vs. 0.507; 1.042 vs. 0.403, respectively), and stop codon mutations more frequent in the OBI sequences (OBI: 2/26, 7.7% vs. CONTROL 0/31, 0%). However, none of these differences was statistically significant (P = 0.237, 0.199, 0.201, respectively). In summary, the prevalence of OBI among HBsAg-negative people with a family history of chronic HBV infection was significantly higher than that in Chinese blood donors. However, S region mutations and the escape mechanism are not likely to be the major causes of increased prevalence of OBI.
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Affiliation(s)
- Zhenhua Zhang
- Department of Infectious Diseases, The First Affiliated Hospital, Anhui Medical University, Hefei, 230022, China
| | - Ling Zhang
- Department of Infectious Diseases, The First Affiliated Hospital, Anhui Medical University, Hefei, 230022, China
| | - Yu Dai
- Department of Infectious Diseases, The First Affiliated Hospital, Anhui Medical University, Hefei, 230022, China
| | - Lei Jin
- Department of Infectious Diseases, The First Affiliated Hospital, Anhui Medical University, Hefei, 230022, China
| | - Binghu Sun
- Department of Infectious Diseases, The First Affiliated Hospital, Anhui Medical University, Hefei, 230022, China
| | - Qian Su
- Department of Infectious Diseases, The First Affiliated Hospital, Anhui Medical University, Hefei, 230022, China
| | - Xu Li
- Department of Infectious Diseases, The First Affiliated Hospital, Anhui Medical University, Hefei, 230022, China
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7
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Boccia S, Miele L, Panic N, Turati F, Arzani D, Cefalo C, Amore R, Bulajic M, Pompili M, Rapaccini G, Gasbarrini A, La Vecchia C, Grieco A. The effect of CYP, GST, and SULT polymorphisms and their interaction with smoking on the risk of hepatocellular carcinoma. BIOMED RESEARCH INTERNATIONAL 2015; 2015:179867. [PMID: 25654087 PMCID: PMC4310264 DOI: 10.1155/2015/179867] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/16/2014] [Revised: 06/19/2014] [Accepted: 06/19/2014] [Indexed: 12/17/2022]
Abstract
Aim. The aim of our study was to assess whether selected single nucleotide polymorphisms of CYP1A1 and 2E1, GSTM1, GSTT1, and SULT1A1 influence susceptibility towards HCC, considering their interaction with cigarette smoking. Methods. We recruited HCC cases and controls among patients admitted to the hospital "Agostino Gemelli," from January 2005 until July 2010. Odds ratios (OR) of HCC were derived from unconditional multiple logistic regression. Gene-gene and gene-smoking interaction were quantified by computing the attributable proportion (AP) due to biological interaction. Results. The presence of any CYP2E1 (*) 5B variant allele (OR: 0.23; 95% CI: 0.06-0.71) and CYP2E1 (*) 6 variant allele (OR: 0.08; 95% CI: 0.01-0.33) was inversely related to HCC. There was a borderline increased risk among carriers of combined CYP1A1 (*) 2A and SULT1A1 variant alleles (OR: 1.67; 95% CI: 0.97-3.24). A significant biological interaction was observed between GSTT1 and smoking (AP = 0.48; 95% CI: 0.001-0.815), with an OR of 3.13 (95% CI: 1.69-5.82), and borderline significant interaction was observed for SULT1A1 and smoking (AP = 0.36; 95% CI: -0.021-0.747), with an OR of 3.05 (95% CI: 1.73-5.40). Conclusion. CYP2E1 (*) 5B and CYP2E1 (*) 6 polymorphisms have a favourable effect on the development of HCC, while polymorphisms of GSTT1 and SULT1A1 might play role in increasing the susceptibility among smokers.
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Affiliation(s)
- Stefania Boccia
- Institute of Public Health, Section of Hygiene, Department of Public Health, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy
- IRCCS San Raffaele Pisana, Via della Pisana 235, 00163 Rome, Italy
| | - Luca Miele
- Institute of Internal Medicine, Gemelli Hospital, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy
- Internal Medicine and Gastroenterology Unit, Complesso Integrato Columbus, Via Giuseppe Moscati 31-33, 00168 Rome, Italy
| | - Nikola Panic
- Institute of Public Health, Section of Hygiene, Department of Public Health, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy
- University Clinical-Hospital Center “Dr Dragisa Misovic-Dedinje”, Milana Tepica 1, 11000 Belgrade, Serbia
| | - Federica Turati
- Department of Epidemiology, IRCCS Istituto di Ricerche Farmacologiche “Mario Negri”, Via La Masa 19, 20156 Milan, Italy
| | - Dario Arzani
- Institute of Public Health, Section of Hygiene, Department of Public Health, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy
| | - Consuelo Cefalo
- Institute of Internal Medicine, Gemelli Hospital, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy
| | - Rosarita Amore
- Institute of Public Health, Section of Hygiene, Department of Public Health, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy
| | - Milutin Bulajic
- University Clinical-Hospital Center “Dr Dragisa Misovic-Dedinje”, Milana Tepica 1, 11000 Belgrade, Serbia
- Faculty of Medicine, University of Belgrade, Dr Subotica 8, 11000 Belgrade, Serbia
| | - Maurizio Pompili
- Internal Medicine and Gastroenterology Division, Gemelli Hospital, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1,
00168 Rome, Italy
| | - Gianlodovico Rapaccini
- Institute of Internal Medicine, Gemelli Hospital, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy
- Internal Medicine and Gastroenterology Unit, Complesso Integrato Columbus, Via Giuseppe Moscati 31-33, 00168 Rome, Italy
| | - Antonio Gasbarrini
- Internal Medicine and Gastroenterology Division, Gemelli Hospital, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1,
00168 Rome, Italy
| | - Carlo La Vecchia
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Via Festa del Perdono 7, 20122 Milan, Italy
| | - Antonio Grieco
- Institute of Internal Medicine, Gemelli Hospital, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy
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Liu L, Li L, Zhou S, Jiang Q, Chen S, Gao Y, Chen Y. Familial correlations of onset age of hepatocellular carcinoma: a population-based case-control family study. PLoS One 2014; 9:e108391. [PMID: 25247419 PMCID: PMC4172774 DOI: 10.1371/journal.pone.0108391] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2014] [Accepted: 08/21/2014] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND There was lack of evidence for familial aggregation in onset age of hepatocellular carcinoma (HCC) in Chinese population. We conducted a population-based case-control family study to examine familial correlation of age of HCC onset in Taixing, China. METHODS A total of 202 cases and 202 matched controls as well as their relatives were included in the study. Lifetime cumulative risks of HCC were estimated using the Kaplan-Meier approach. Cross ratios (CRs) were obtained from stratified Cox proportional hazard models, to assess the familial correlation of onset age. RESULTS The mean age of HCC onset was decreased as increasing number of HCC cases in a family. The onset age was the earliest for first-degree relatives, intermediate for second-degree relatives, and latest for non-blood relatives (spouse) (log-rank test, P<0.01). The onset age was significantly correlated between probands and their relatives. In stratified Cox proportional hazard models, the CRs for the probands versus their fathers, mothers, siblings and uncles/aunts were 6.25 (95% confidence interval (CI): 1.84-21.25), 9.81 (95% CI: 1.24-77.56), 6.22 (95% CI: 1.37-28.36) and 3.24 (95% CI: 1.26-8.33), respectively. After adjustment for hepatitis B virus infection, the CRs remained significant. CONCLUSION This current study suggested a significant correlation of onset age for HCC among blood relatives. Familial HCC cases yielded earlier age of onset and their relatives have higher HCC risk in early age, highlighting intensive surveillance should be start at an earlier age for individuals with family history of HCC.
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Affiliation(s)
- Li Liu
- Department of Epidemiology and Biostatistics and Guangdong Key Lab of Molecular Epidemiology, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, China
| | - Lixia Li
- Department of Epidemiology and Biostatistics and Guangdong Key Lab of Molecular Epidemiology, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, China
| | - Shudong Zhou
- Department of Epidemiology and Biostatistics and Guangdong Key Lab of Molecular Epidemiology, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, China
| | - Qingwu Jiang
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Sidong Chen
- Department of Epidemiology and Biostatistics and Guangdong Key Lab of Molecular Epidemiology, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, China
| | - Yanhui Gao
- Department of Epidemiology and Biostatistics and Guangdong Key Lab of Molecular Epidemiology, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, China
- * E-mail:
| | - Yue Chen
- Department of Epidemiology and Community Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
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Fernández-Rodríguez CM, Gutiérrez-García ML. Prevention of hepatocellular carcinoma in patients with chronic hepatitis B. World J Gastrointest Pharmacol Ther 2014; 5:175-182. [PMID: 25133046 PMCID: PMC4133443 DOI: 10.4292/wjgpt.v5.i3.175] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2014] [Revised: 04/01/2014] [Accepted: 07/12/2014] [Indexed: 02/06/2023] Open
Abstract
Patients with chronic hepatitis B are at significant risk for hepatocellular carcinoma (HCC). Globally, over half a million people each year are diagnosed with HCC, with marked geographical variations. Despite overwhelming evidence for a causal role of hepatitis B virus (HBV) infection in the development of HCC and a well-established relationship between high baseline hepatitis B viral load and cumulative risk of HCC, the molecular basis for this association has not been fully elucidated. In addition, a beneficial role for antiviral therapy in preventing the development of HCC has been difficult to establish. This review examines the biological and molecular mechanisms of HBV-related hepatocarcinogenesis, recent results on the effect of modern nucleos(t)ides on the rate of HCC development in high risk HBV cohorts and the potential mechanisms by which long-term antiviral therapy with potent inhibitors of HBV replication might reduce the risk of HCC in patients with chronic hepatitis B. Although evidence from randomized controlled trials shows the favourable effects of antiviral agents in achieving profound and durable suppression of HBV DNA levels while improving liver function and histology, robust evidence of other long-term clinical outcomes, such as prevention of HCC, are limited.
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10
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Zhong Y, Yan J, Deng M, Hu K, Yao Z, Zou Y, Xu R. Impaired phosphate and tension homologue deleted on chromosome 10 expression and its prognostic role in radical surgery for hepatocellular carcinoma with family aggregation resulting from hepatitis B and liver cirrhosis. Exp Biol Med (Maywood) 2013; 238:866-73. [PMID: 23828588 DOI: 10.1177/1535370213494654] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
This study aimed to retrospectively investigate the expression of the phosphate and tension homologue deleted on chromosome 10 (PTEN) protein and its prognostic role in hepatocellular carcinoma (HCC) with family aggregation resulting from hepatitis B and liver cirrhosis, which have not been established. Immunohistochemical analysis was performed to evaluate the PTEN protein expression in HCC and paired para-cancerous tissues from 79 patients with HCC caused by hepatitis B and liver cirrhosis. Of these cases, 34 represented HCC with family aggregation (HCCF group), and 45 represented HCC with no family aggregation (HCCN group). Follow-up data were collected for 3 months to 10 years and analysed for HCC recurrence, survival time and prognostic risk factors. The expression of the PTEN protein in the HCC tissue was dramatically lower in the HCCF group than in the HCCN group. The six-month, one-year and two-year overall recurrence (OR) rates of the HCCF group were significantly higher than those of the HCCN group. The one-year, two-year and five-year overall survival (OS) rates of the HCCF group were lower than those of the HCCN group. Impaired PTEN protein expression was an independent prognostic risk factor that was significantly correlated with OR and OS in HCC patients. Dramatically impaired PTEN protein expression in HCC patients with family aggregation resulting from hepatitis B and liver cirrhosis was correlated with OR and OS, and impaired PTEN expression was an independent risk factor for prognosis after radical surgery.
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Affiliation(s)
- Yuesi Zhong
- Department of Hepatobiliary Surgery, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
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Zhong DN, Ning QY, Wu JZ, Zang N, Wu JL, Hu DF, Luo SY, Huang AC, Li LL, Li GJ. Comparative proteomic profiles indicating genetic factors may involve in hepatocellular carcinoma familial aggregation. Cancer Sci 2012; 103:1833-8. [PMID: 22726459 DOI: 10.1111/j.1349-7006.2012.02368.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2012] [Revised: 06/03/2012] [Accepted: 06/14/2012] [Indexed: 12/23/2022] Open
Abstract
Familial aggregation of hepatocellular carcinoma (HCC), the third leading cause of cancer death worldwide, has shown to be a common phenomenon. We investigated the association between the genetic background and HCC familial aggregation. Serum samples were collected from HCC family members and normal control family members for screening the differentially expressed protein peaks with the approach of surface-enhanced laser desorption ionization time-of-flight mass spectrometry. Potential genetically associated protein peaks were selected and further identified by matrix assisted laser desorption ionization-time of flight mass spectrometry. A panel of six protein peaks (m/z 6432.94, 8478.35, 9381.91, 17284.67, 17418.34, and 18111.04) were speculated to reflect the genetic susceptibility of HCC familial aggregation. Three of them (m/z 6432.94, 8478.35, and 9381.91) were selected to identify as the candidate proteins. Nine identified proteins, including mostly apolipoprotein family (ApoA1, ApoA2, ApoC3, ApoE) and serum amyloid A protein (SAA), were found overexpressed in the multiple HCC cases family members. The comparative proteomic profiles have suggested that genetic factors ought to be taken into account for familial aggregation of HCC.
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Affiliation(s)
- Da-Ni Zhong
- Department of Infectious Diseases, First Affiliated Hospital, Guangxi Medical University, Nanning, China
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Tanaka M, Katayama F, Kato H, Tanaka H, Wang J, Qiao YL, Inoue M. Hepatitis B and C virus infection and hepatocellular carcinoma in China: a review of epidemiology and control measures. J Epidemiol 2011. [PMID: 22041528 DOI: 10.2188/jea.je20100190.] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/28/2022] Open
Abstract
China has one of the highest carrier prevalences of hepatitis B virus (HBV) in the world: nearly 10% of the general population. The disease burden of HBV infection and hepatocellular carcinoma (HCC) is also believed to be among the world's largest, and that of hepatitis C virus (HCV) infection is likely to be substantial as well. However, the epidemiology and measures to control HBV and HCV infection in China remain relatively unknown outside the country. We review the epidemiology of HBV and HCV infection, the disease burden of and risk factors for HCC, and current control measures against HBV and HCV infection in China. We also discuss the relevant literature and implications for future studies of hepatitis and HCC in China.
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Affiliation(s)
- Masahiro Tanaka
- Department of Cancer Control and Statistics, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
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Tanaka M, Katayama F, Kato H, Tanaka H, Wang J, Qiao YL, Inoue M. Hepatitis B and C virus infection and hepatocellular carcinoma in China: a review of epidemiology and control measures. J Epidemiol 2011; 21:401-416. [PMID: 22041528 PMCID: PMC3899457 DOI: 10.2188/jea.je20100190] [Citation(s) in RCA: 239] [Impact Index Per Article: 17.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2011] [Accepted: 06/20/2011] [Indexed: 12/14/2022] Open
Abstract
China has one of the highest carrier prevalences of hepatitis B virus (HBV) in the world: nearly 10% of the general population. The disease burden of HBV infection and hepatocellular carcinoma (HCC) is also believed to be among the world's largest, and that of hepatitis C virus (HCV) infection is likely to be substantial as well. However, the epidemiology and measures to control HBV and HCV infection in China remain relatively unknown outside the country. We review the epidemiology of HBV and HCV infection, the disease burden of and risk factors for HCC, and current control measures against HBV and HCV infection in China. We also discuss the relevant literature and implications for future studies of hepatitis and HCC in China.
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Affiliation(s)
- Masahiro Tanaka
- Department of Cancer Control and Statistics, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
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Liu HB, Qian ZY, Wang BS, Tong SX. Detection of markers of hepatitis viral infection in the tissue of bile duct carcinoma. Chin Med J (Engl) 2008; 121:1143-1144. [PMID: 18706237 DOI: 10.1097/00029330-200806020-00022] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Affiliation(s)
- Hou-bao Liu
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China
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Bolukbas C, Bolukbas FF, Kocyigit A, Aslan M, Selek S, Bitiren M, Ulukanligil M. Relationship between levels of DNA damage in lymphocytes and histopathological severity of chronic hepatitis C and various clinical forms of hepatitis B. J Gastroenterol Hepatol 2006; 21:610-6. [PMID: 16638108 DOI: 10.1111/j.1440-1746.2005.04069.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
BACKGROUND AND AIM A significant proportion of cancer is attributable to DNA damage caused by chronic infection and inflammation. Because both hepatitis B and C viruses (HBV and HCV, respectively) cause chronic infection and inflammatory disease, the aim of the present study was to investigate whether there is a difference in peripheral DNA damage in patients with chronic HCV compared with patients with chronic HBV; and whether there is an association in the level of peripheral DNA damage with a natural history of HBV infection. METHODS Twenty patients with chronic hepatitis C, 20 patients with chronic hepatitis B, 11 patients with cirrhosis secondary to hepatitis B, 12 inactive hepatitis B s antigen (HBsAg) carriers and 21 healthy subjects were included in the study. The DNA damage in lymphocytes was determined using the alkaline comet assay. RESULTS Although the chronic hepatitis C group had similar levels of DNA damage compared with patients with cirrhosis due to hepatitis B (P > 0.05) and non-cirrhotic patients with chronic hepatitis B (P > 0.05), they had higher levels of DNA damage compared with inactive HBsAg carriers (P = 0.021) and controls (P = 0.001). Hepatitis B cirrhotic patients and patients with chronic hepatitis B had significantly higher levels of DNA damage than inactive HBsAg carriers (P = 0.002 and P = 0.012, respectively) and controls (both P = 0.001). Linear logistic regression analysis showed that chronic hepatitis C and HBV-related cirrhosis were discriminators in determining DNA damage in lymphocytes (beta 0.424 and P = 0.013, beta 0.393 and P = 0.016, respectively). CONCLUSIONS Chronic hepatitis C, based on the severity of liver disease, or cirrhosis as an advanced form of HBV infection increase DNA damage in lymphocytes independently of confounding factors such as age, gender, body mass index and smoking habits.
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Affiliation(s)
- Cengiz Bolukbas
- Department of Internal Medicine, Gastroenterology Division, Harran University, Medical Faculty, Sanliurfa, Turkey.
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Yao F, Guo JM, Xu CF, Lou YL, Xiao BX, Zhou WH, Chen J, Hu YR, Liu Z, Hong GF. Detecting AFP mRNA in peripheral blood of the patients with hepatocellular carcinoma, liver cirrhosis and hepatitis. Clin Chim Acta 2005; 361:119-27. [PMID: 15993394 DOI: 10.1016/j.cccn.2005.05.005] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2005] [Revised: 05/03/2005] [Accepted: 05/05/2005] [Indexed: 12/27/2022]
Abstract
BACKGROUND The low frequency of disseminated carcinoma cells in the blood now makes immunomagnetic bead sorting and reverse transcriptase-polymerase chain reaction (RT-PCR) technique more popular. METHODS Three milliliters of peripheral blood were collected from 91 patients and 18 normal donors. The circulating carcinoma cells were enriched with CD45 and Ber-EP4 immunomagnetic beads. The alpha-fetoprotein (AFP) mRNA was amplified with nested RT-PCR. RESULTS The total positive detection rate was 72.1%, 43.8%, 25.0%, 100%, and 66.7% in patients with hepatocellular carcinoma (HCC) untreated, liver cirrhosis (LC), hepatitis, metastasis liver cancer, and postsurgery of hepatocellular carcinoma, respectively. There was a significant difference among the patients with HCC, LC and hepatitis (HCC vs. LC, P<0.05; HCC vs. hepatitis, P<0.01) and between Class A and B of the HCC patients (P<0.05). Meanwhile, AFP mRNA was markedly expressed in HCC patients compared to the patients with no HCC (LC and hepatitis). The levels of aspartate transaminase (AST) and gamma-glutamyltranspeptidase (GGT) were significantly different in AFP mRNA-positive patients with autoimmune chronic active hepatitis B (CAHB) or LC in contrast to the corresponding negative patients. CONCLUSION Combining negative and positive immunomagnetic bead sorting and RT-PCR technique can effectively detect circulating tumor cells. AFP mRNA is a more reliable marker of metastasis compared to serum AFP.
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Affiliation(s)
- Feng Yao
- Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China
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Zhou SF, Xie XX, Bin YH, Lan L, Chen F, Luo GR. Identification of HCC-22-5 tumor-associated antigen and antibody response in patients. Clin Chim Acta 2005; 366:274-80. [PMID: 16356486 DOI: 10.1016/j.cca.2005.10.026] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2005] [Revised: 10/19/2005] [Accepted: 10/26/2005] [Indexed: 02/07/2023]
Abstract
BACKGROUND Serological identification of antigens by recombinant expression cloning (SEREX) is a promising method used to analyze tumor-associated antigen (TAA). Nineteen primary HCC-associated antigens have been found from a HCC cDNA library using autogenous serum by the SEREX approach. We searched for HCC-associated antigens and applied them to HCC diagnosis. METHODS Nine of 19 primaries HCC-associated antigens identified by SEREX method were tested their immune response again with distinct allogeneic sera. One of the screened HCC-associated antigens, HCC-22-5 was recombined and expressed and made the frequency analysis of its seropositivity in various patients using the methods of Western-blot and ELISA. RESULTS SEREX analysis showed that 9 primary HCC-associated antigens had high-titered IgG antibody in the majority of HCC patients. Western-Blot method confirmed that 3/7 HCC patients had antibodies against HCC-22-5, which demonstrated that expressed HCC-22-5 antigen had the character of antigen. Sera samples from 341 patients and 80 normal individuals have been tested for autoantibodies against HCC-22-5 by ELISA method. The results found that 51/128 of HCC, 11/76 of chronic hepatitis, 11/22 of liver cirrhosis and 8/54 of nasopharynx cancer patients had antibodies against HCC-22-5. No antibody response to HCC-22-5 had been found in the sera of 7 lung cancers, 54 gastric-intestine patients and 80 normal individuals. The groups of HCC and liver cirrhosis had higher antibody positive rate than that of other groups (p<0.05). In the HCC sera with alpha-fetoprotein (AFP) negative, the positive rate of HCC-22-5 was as high as 78.9%. CONCLUSIONS HCC-22-5 can be used for HCC serologic screening, especially for the patients with AFP negative.
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MESH Headings
- Amino Acid Sequence
- Antibody Formation/immunology
- Antigens, Neoplasm/genetics
- Antigens, Neoplasm/immunology
- Antigens, Neoplasm/metabolism
- Base Sequence
- Blotting, Western
- Carcinoma, Hepatocellular/blood
- Carcinoma, Hepatocellular/genetics
- Carcinoma, Hepatocellular/immunology
- Carrier Proteins/genetics
- DNA, Complementary/chemistry
- DNA, Complementary/genetics
- Electrophoresis, Polyacrylamide Gel
- Enzyme-Linked Immunosorbent Assay
- Hepatitis, Chronic/blood
- Hepatitis, Chronic/immunology
- Humans
- Immunoglobulin G/blood
- Immunoglobulin G/immunology
- Liver Cirrhosis/blood
- Liver Cirrhosis/immunology
- Liver Neoplasms/blood
- Liver Neoplasms/genetics
- Liver Neoplasms/immunology
- Maltose-Binding Proteins
- Molecular Sequence Data
- Recombinant Fusion Proteins/genetics
- Recombinant Fusion Proteins/immunology
- Recombinant Fusion Proteins/metabolism
- Sequence Analysis, DNA
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Affiliation(s)
- Su-Fang Zhou
- The School of Pre-clinical Sciences, Guangxi Medical University, 22 Shuangrong Road, Nanning 530021, China.
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