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Toyoda H, Koshiyama Y, Yasuda S, Kumada T, Chayama K, Akita T, Tanaka J. Effect of previous infection with hepatitis B virus on the incidence of hepatocellular carcinoma after sustained virologic response in patients with chronic hepatitis C virus infection. J Viral Hepat 2024; 31:137-142. [PMID: 38146596 DOI: 10.1111/jvh.13907] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Revised: 10/30/2023] [Accepted: 12/08/2023] [Indexed: 12/27/2023]
Abstract
Previous infection with hepatitis B virus (HBV), which is assessed by HBV core antibody (HBcAb) or surface antibody (HBsAb) titres, has reportedly been associated with an increased risk of developing hepatocellular carcinoma (HCC). We investigated the influence of previous HBV infection on the incidence of HCC in patients with hepatitis C virus (HCV) infection who achieved eradication of HCV, that is sustained virologic response (SVR). Both HBcAb and HBsAb were measured in a total of 1214 patients with HCV infection who had not been coinfected with HBV, as determined by both negative HBs antigen and HBV DNA, and in whom SVR was confirmed. Patients were followed up for a median of 5.7 years, and the incidence of post-SVR HCC was compared based on HBcAb and/or HBsAb. In both univariate and multivariate analyses, the incidence of post-SVR HCC did not differ based on the presence of HBcAb or HBsAb. In conclusion, previous HBV infection has no impact on the incidence of HCC in patients with HCV after SVR.
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Affiliation(s)
- Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Yuichi Koshiyama
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Satoshi Yasuda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Takashi Kumada
- Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan
| | - Kazuaki Chayama
- Hiroshima Institute of Life Sciences, Hiroshima, Japan
- RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
- Collaborative Research Laboratory of Medical Innovation, Hiroshima University, Hiroshima, Japan
| | - Tomoyuki Akita
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
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Yeo SJ, Lee HS, Jang BI, Kim ES, Jeon SW, Kim SK, Kim KO, Lee YJ, Lee HJ, Park KS, Jung YJ, Kim EY, Yang CH. Nonimmunity against hepatitis B virus infection in patients newly diagnosed with inflammatory bowel disease. Intest Res 2018; 16:400-408. [PMID: 30090039 PMCID: PMC6077318 DOI: 10.5217/ir.2018.16.3.400] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2017] [Revised: 01/15/2018] [Accepted: 01/16/2018] [Indexed: 12/16/2022] Open
Abstract
Background/Aims This study aimed to elucidate the prevalence of hepatitis B virus (HBV) serologic markers in Korean patients newly diagnosed with, but not yet treated for inflammatory bowel disease (IBD). Methods We prospectively enrolled 210 patients newly diagnosed with IBD (109 with ulcerative colitis and 101 with Crohn's disease). Hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc) levels were measured and compared with those of 1,100 sex- and age-matched controls. Results The prevalence of chronic HBV infection (positive HBsAg, positive anti-HBc, and negative anti-HBs results) and past infection (negative HBsAg, positive anti-HBc, and positive or negative anti-HBs results) were not significantly different between the patients and controls (chronic HBV infection: IBD, 3.8% vs. control, 4.9%, P=0.596; past infection: IBD, 26.2% vs. control, 28.8%, P=0.625). The patients with IBD aged <20 years were at a higher susceptibility risk (nonimmune) for HBV infection than the controls (IBD, 41.5% vs. control, 22.4%; P=0.018). In the multivariate analysis, an age of <20 years (P=0.024) and symptom duration of ≥12 months before diagnosis (P=0.027) were identified as independent risk factors for nonimmunity against HBV infection. Conclusions The patients newly diagnosed with IBD were susceptible to HBV infection. The frequency of nonimmunity was high, especially in the patients aged <20 years and those with a longer duration of symptoms before diagnosis. Therefore, it is necessary to screen for HBV serologic markers and generate a detailed vaccination plan for patients newly diagnosed with IBD.
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Affiliation(s)
- Seong Jae Yeo
- Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Hyun Seok Lee
- Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Byung Ik Jang
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | - Eun Soo Kim
- Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Seong Woo Jeon
- Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Sung Kook Kim
- Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Kyeong Ok Kim
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | - Yoo Jin Lee
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Hyun Jik Lee
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Kyung Sik Park
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Yun Jin Jung
- Department of Internal Medicine, Daegu Fatima Hospital, Daegu, Korea
| | - Eun Young Kim
- Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, Korea
| | - Chang Heon Yang
- Department of Internal Medicine, Dongguk University School of Medicine, Gyeongju, Korea
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Loggi E, Gitto S, Galli S, Minichiello M, Conti F, Grandini E, Scuteri A, Vitale G, Di Donato R, Cursaro C, Furlini G, Andreone P. Hepatitis B virus reactivation among hepatitis C patients treated with direct-acting antiviral therapies in routine clinical practice. J Clin Virol 2017; 93:66-70. [PMID: 28654775 DOI: 10.1016/j.jcv.2017.05.021] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2017] [Revised: 05/22/2017] [Accepted: 05/30/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND Hepatitis B (HBV) reactivation in chronic hepatitis C (CHC) patients treated with IFN-free direct acting antiviral (DAA) therapies has recently emerged as a potential risk. Given the potential burden of this issue, further data are needed to establish its actual clinical impact. OBJECTIVES The aim of the present study was to analyze the occurrence of HBV reactivation in a cohort of CHC patient treated with DAAs in routine clinical practice. STUDY DESIGN Consecutive CHC patients with different genotypes, treated with DAA between January 2015 and January 2016 were included in the study. Subjects had been tested for HBsAg and anti-HBc antibodies before antiviral therapy. HBV-DNA levels were examined in anti-HBc positive patients at baseline and 24 weeks after the end of treatment. Post-treatment HBsAg determination was performed in case of HBV-DNA positivity. Serum anti-HBs kinetics was analysed in anti-HBs and anti-HBc positive subjects. RESULTS A cohort of 137 consecutive HCV patients treated with IFN-free regimens in routine clinical practice was evaluated. From this cohort, plasma samples of 44 subjects with positive serology for HBV (anti-HBc positive) were tested for HBV-DNA levels at baseline and 24 weeks after the end of treatment. Two of them were HBsAg-positive, while the others had signs of a past HBV exposure (HBsAg-negative±HBsAb-positive). No reactivation was found in HBcAb-positive and HBsAg-negative subjects. In the two HBsAg-positive, one experienced an increase in HBV-DNA levels of ≥2 log10 IU/mL during treatment. However, the reactivation was without clinical impact and, most important, was followed by HBsAg loss. CONCLUSIONS Based on our experience, a past HBV infection seems not to be a condition predisposing to HBV reactivation. On the contrary, in HBsAg-positive subjects not in suppressive treatment with nucleos(t)ide analogs, regular monitoring of HBV-DNA during and after DAA treatment should be considered.
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Affiliation(s)
- Elisabetta Loggi
- Dipartimento di Scienze Mediche e Chirurgiche & Centro Studi Ricerche sulle Epatiti, Programma Dipartimentale ITEC, Azienda Ospedaliero-Universitaria Policlinico di Sant'Orsola, Bologna, Italy; Unità Operativa di Microbiologia e Virologia, Azienda Ospedaliero-Universitaria Sant'Orsola-Malpighi, Bologna, Italy
| | - Stefano Gitto
- Dipartimento di Scienze Mediche e Chirurgiche & Centro Studi Ricerche sulle Epatiti, Programma Dipartimentale ITEC, Azienda Ospedaliero-Universitaria Policlinico di Sant'Orsola, Bologna, Italy
| | - Silvia Galli
- Unità Operativa di Microbiologia e Virologia, Azienda Ospedaliero-Universitaria Sant'Orsola-Malpighi, Bologna, Italy
| | - Mario Minichiello
- Unità Operativa di Microbiologia e Virologia, Azienda Ospedaliero-Universitaria Sant'Orsola-Malpighi, Bologna, Italy
| | - Fabio Conti
- Dipartimento di Scienze Mediche e Chirurgiche & Centro Studi Ricerche sulle Epatiti, Programma Dipartimentale ITEC, Azienda Ospedaliero-Universitaria Policlinico di Sant'Orsola, Bologna, Italy
| | - Elena Grandini
- Dipartimento di Scienze Mediche e Chirurgiche & Centro Studi Ricerche sulle Epatiti, Programma Dipartimentale ITEC, Azienda Ospedaliero-Universitaria Policlinico di Sant'Orsola, Bologna, Italy
| | - Alessandra Scuteri
- Dipartimento di Scienze Mediche e Chirurgiche & Centro Studi Ricerche sulle Epatiti, Programma Dipartimentale ITEC, Azienda Ospedaliero-Universitaria Policlinico di Sant'Orsola, Bologna, Italy
| | - Giovanni Vitale
- Dipartimento di Scienze Mediche e Chirurgiche & Centro Studi Ricerche sulle Epatiti, Programma Dipartimentale ITEC, Azienda Ospedaliero-Universitaria Policlinico di Sant'Orsola, Bologna, Italy
| | - Roberto Di Donato
- Dipartimento di Scienze Mediche e Chirurgiche & Centro Studi Ricerche sulle Epatiti, Programma Dipartimentale ITEC, Azienda Ospedaliero-Universitaria Policlinico di Sant'Orsola, Bologna, Italy
| | - Carmela Cursaro
- Dipartimento di Scienze Mediche e Chirurgiche & Centro Studi Ricerche sulle Epatiti, Programma Dipartimentale ITEC, Azienda Ospedaliero-Universitaria Policlinico di Sant'Orsola, Bologna, Italy
| | - Giuliano Furlini
- Unità Operativa di Microbiologia e Virologia, Azienda Ospedaliero-Universitaria Sant'Orsola-Malpighi, Bologna, Italy
| | - Pietro Andreone
- Dipartimento di Scienze Mediche e Chirurgiche & Centro Studi Ricerche sulle Epatiti, Programma Dipartimentale ITEC, Azienda Ospedaliero-Universitaria Policlinico di Sant'Orsola, Bologna, Italy.
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Wang Q, Klenerman P, Semmo N. Significance of anti-HBc alone serological status in clinical practice. Lancet Gastroenterol Hepatol 2017; 2:123-134. [DOI: 10.1016/s2468-1253(16)30076-0] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2016] [Revised: 07/26/2016] [Accepted: 07/29/2016] [Indexed: 02/07/2023]
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Sagnelli C, Macera M, Pisaturo M, Zampino R, Coppola M, Sagnelli E. Occult HBV infection in the oncohematological setting. Infection 2016; 44:575-582. [PMID: 27076347 DOI: 10.1007/s15010-016-0891-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2015] [Accepted: 03/07/2016] [Indexed: 12/15/2022]
Abstract
INTRODUCTION Occult hepatitis B infection (OBI), a virological condition characterized by a low release of Hepatitis B Virus (HBV) from liver cells and low HBV-DNA levels in serum and/or liver tissue of HBsAg-negative subjects, may reactivate in oncohematological patients undergoing immunosuppression by aggressive chemotherapy or hematopoietic stem cell transplantation. The entity of OBI reactivation varies from an increase in HBV replication without liver damage to an active HBV replication followed by liver cell necrosis, frequently severe and in some cases life threatening. Because of a possible severe outcome associated with OBI reactivation (hepatic failure or death due to the discontinuation of chemotherapy), prophylaxis with anti-HBV nucleot(s)ide analogues is recommended in relation to the foreseeable degree of immunosuppression. MATERIALS AND METHODS This review article focuses on the clinical impact of OBI in the oncohematological setting and is addressed to all health care workers having in care oncohematological patients or involved in the treatment of HBV infection and OBI prophylaxis. CONCLUSION International guidelines have indicated lamivudine prophylaxis in hematopoietic stem cell transplantation and when high-dose corticosteroids or anti-CD20 or anti-CD52 monoclonal antibodies are used. Entecavir or tenofovir should replace lamivudine for patients with advanced liver diseases for whom reactivation of OBI may be life threatening. When anti-CD20 or anti-CD52 sparing schedules or other non-aggressive chemotherapies are used, monitoring may be indicated, but very early treatment with highly effective antiviral drugs (entecavir or tenofovir) should be administered once a reactivation of OBI has occurred.
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Affiliation(s)
- C Sagnelli
- Department of Clinical and Experimental Medicine and Surgery "F. Magrassi e A. Lanzara", Second University of Naples, 80131, Naples, Italy
| | - M Macera
- Azienda Ospedaliera Universitaria-Second University of Naples, 80131, Naples, Italy
| | - M Pisaturo
- Division of Infectious Diseases, AORN Sant'Anna e San Sebastiano di Caserta, 81100, Caserta, Italy
| | - R Zampino
- Department of Medical, Surgical, Neurological, Metabolic and Geriatric Sciences, Second University of Naples, 80131, Naples, Italy
| | - M Coppola
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, Second University of Naples, Via: L. Armanni 5, 80131, Naples, Italy
| | - E Sagnelli
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, Second University of Naples, Via: L. Armanni 5, 80131, Naples, Italy.
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El Din Ahmed Elsawaf G, Abd El Kader Mahmoud O, Mohamed Shawky S, Mostafa Mostafa Mohamed H, Hezam Ahmed Alsumairy H. Impact of occult hepatitis B virus infection on antiviral therapy in chronic hepatitis C patients. ALEXANDRIA JOURNAL OF MEDICINE 2015. [DOI: 10.1016/j.ajme.2014.10.001] [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: 10/24/2022] Open
Affiliation(s)
| | | | | | | | - Hafez Hezam Ahmed Alsumairy
- Master of Clinical Microbiology and Immunology, Faculty of Applied Medical Sciences, Jordan University of Science and Technology, Jordan
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Rong G, Wang H, Bowlus CL, Wang C, Lu Y, Zeng Z, Qu J, Lou M, Chen Y, An L, Yang Y, Gershwin ME. Incidence and risk factors for hepatocellular carcinoma in primary biliary cirrhosis. Clin Rev Allergy Immunol 2015; 48:132-141. [PMID: 25762349 DOI: 10.1007/s12016-015-8483-x] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The incidence, risk factors, and clinical features of hepatocellular carcinoma (HCC) in primary biliary cirrhosis (PBC) have been a long-standing subject of interest. We took advantage of a large cohort of 1865 well-defined Chinese patients with PBC for whom follow-up was conducted for up to 20 years to study the incidence of HCC. Our goal was to address the incidence and prevalence of HCC in PBC and the risk factors, including hepatitis B virus (HBV) infection, and finally to compare the tumor characteristics of PBC-related HCC, including size, location, mortality, and long-term outcomes, to that of HBV-related HCC. In this cohort, HCC occurred in 70 of 1865 PBC patients with a prevalence of 3.75 % and an incidence of 0.66 cases per 100 patient-years. The 5- and 10-year cumulative incidences were 2.6 % (95 % confidence interval (CI) 1.8-3.4) and 8.9 % (95 % CI 5.5-12.3), respectively. Age >54 years (odds ratio [OR] = 5.5, 95 % CI 3.0-10.1, p = 0.001), male sex (OR = 2.2, 95 % CI 1.2-4.0, p = 0.001), co-existence of diabetes mellitus (DM) (OR = 3.1, 95 % CI 1.6-6.2, p = 0.002), and previous HBV infection (OR = 6.6, 95 % CI 3.7-11.9, p = 0.001) were independently associated with the development of HCC. The tumor size, number, location, and 5-year survival were not significantly different in PBC-related HCC compared to HBV-related HCC. Alpha-fetoprotein was elevated in only 20 % of the cases with PBC-related HCC. Although HCC was uncommon, occurring in fewer than 5 % of patients, the risk is significantly increased by age, sex, DM, and past HBV infection.
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Affiliation(s)
- Guanghua Rong
- Center of Therapeutic Research for Hepatocellular Carcinoma, The 302 Hospital, 100 Xi Si Huan Middle Road, 100039, Beijing, China,
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Inuzuka T, Ueda Y, Morimura H, Fujii Y, Umeda M, Kou T, Osaki Y, Uemoto S, Chiba T, Marusawa H. Reactivation from occult HBV carrier status is characterized by low genetic heterogeneity with the wild-type or G1896A variant prevalence. J Hepatol 2014; 61:492-501. [PMID: 24798622 DOI: 10.1016/j.jhep.2014.04.033] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2013] [Revised: 04/07/2014] [Accepted: 04/24/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Individuals negative for hepatitis B surface antigen (HBsAg) but positive for antibodies to hepatitis B core antigen (anti-HBc) are at risk of hepatitis B virus (HBV) reactivation under immunosuppressive conditions. We investigated clinical features and viral genetics in patients with reactivation from occult HBV infection triggered by chemotherapy or immunosuppressive therapy. METHODS Clinical courses of 14 individuals originally HBsAg-negative but anti-HBc-positive that experienced HBV reactivation were examined. Ultra-deep sequencing analysis of the entire HBV genome in serum was conducted. Prevalence of the G1896A variant in latently infected livers was determined among 44 healthy individuals that were HBsAg-negative but anti-HBc-positive. RESULTS In 14 cases, HBV reactivation occurred during (n=7) and after (n=7) termination of immunosuppressive therapy. Ultra-deep sequencing revealed that the genetic heterogeneity of reactivated HBV was significantly lower in patients with reactivation from occult HBV carrier status compared with that in patients from HBsAg carrier status. The reactivated viruses in each case were almost exclusively the wild-type G1896 or G1896A variant. The G1896A variant was detected in 42.9% (6/14) of cases, including two cases with fatal liver failure. The G1896A variant was observed in the liver tissue of 11.4% (5/44) of individuals with occult HBV infection. CONCLUSIONS Reactivation from occult HBV infection is characterized by low genetic heterogeneity, with the wild-type G1896 or G1896A variant prevalent.
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Affiliation(s)
- Tadashi Inuzuka
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Yoshihide Ueda
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Hiroki Morimura
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Yosuke Fujii
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Makoto Umeda
- Department of Gastroenterology and Hepatology, Hyogo Prefectural Amagasaki Hospital, Hyogo, Japan
| | - Tadayuki Kou
- Department of Gastroenterology and Hepatology, Kitano Hospital, Osaka, Japan
| | - Yukio Osaki
- Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, Osaka, Japan
| | - Shinji Uemoto
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Tsutomu Chiba
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Hiroyuki Marusawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
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Tsubouchi N, Uto H, Kumagai K, Sasaki F, Kanmura S, Numata M, Moriuchi A, Oketani M, Ido A, Hayashi K, Kusumoto K, Shimoda K, Stuver SO, Tsubouchi H. Impact of antibody to hepatitis B core antigen on the clinical course of hepatitis C virus carriers in a hyperendemic area in Japan: A community-based cohort study. Hepatol Res 2013; 43:1130-8. [PMID: 23413835 PMCID: PMC3710530 DOI: 10.1111/hepr.12075] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2012] [Revised: 01/14/2013] [Accepted: 01/16/2013] [Indexed: 01/01/2023]
Abstract
AIM Subjects positive for antibody to hepatitis B core antigen (HBcAb) and negative for hepatitis B surface antigen (HBsAg) are considered to have occult hepatitis B virus (HBV) infection. The aim of this study was to determine the impact of occult HBV infection on aggravation of the clinical course in hepatitis C virus (HCV) carriers. METHODS A prospective cohort study was performed in 400 subjects who were positive for anti-HCV antibody and negative for HBsAg. Among these subjects, 263 were HCV core antigen positive or HCV RNA positive (HCV carriers). We examined whether the presence of HBcAb affected the clinical course in these HCV carriers from 1996-2005. RESULTS The HBcAb positive rates were 53.6% and 52.6% in HCV carriers and HCV RNA negative subjects, respectively. There were no differences in the incidence of hepatocellular carcinoma (HCC) and cumulative mortality associated with liver-related death between HCV carriers who were positive and negative for HBcAb. In multivariate analysis, age (≥65 years) and alanine aminotransferase level (≥31 IU/L) emerged as independent risk factors for HCC development and liver-related death, but the HBcAb status was not a risk factor. In addition, increased serum hepatic fibrosis markers (measured from 2001-2004) were not associated with HBcAb status. CONCLUSION In our cohort study, the presence of HBcAb had no impact on HCC development, liver-related death and hepatic fibrosis markers in HCV carriers. Thus, our results indicate that occult HBV infection has no impact on the clinical course in HCV carriers.
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Affiliation(s)
- Naoko Tsubouchi
- Digestive and Lifestyle Diseases, Department of Human and
Environmental Sciences, Kagoshima University Graduate School of Medical and Dental
Sciences, Kagoshima, Japan
| | - Hirofumi Uto
- Digestive and Lifestyle Diseases, Department of Human and
Environmental Sciences, Kagoshima University Graduate School of Medical and Dental
Sciences, Kagoshima, Japan
| | - Kotaro Kumagai
- Digestive and Lifestyle Diseases, Department of Human and
Environmental Sciences, Kagoshima University Graduate School of Medical and Dental
Sciences, Kagoshima, Japan
| | - Fumisato Sasaki
- Digestive and Lifestyle Diseases, Department of Human and
Environmental Sciences, Kagoshima University Graduate School of Medical and Dental
Sciences, Kagoshima, Japan
| | - Shuji Kanmura
- Digestive and Lifestyle Diseases, Department of Human and
Environmental Sciences, Kagoshima University Graduate School of Medical and Dental
Sciences, Kagoshima, Japan
| | - Masatsugu Numata
- Digestive and Lifestyle Diseases, Department of Human and
Environmental Sciences, Kagoshima University Graduate School of Medical and Dental
Sciences, Kagoshima, Japan
| | - Akihiro Moriuchi
- Digestive and Lifestyle Diseases, Department of Human and
Environmental Sciences, Kagoshima University Graduate School of Medical and Dental
Sciences, Kagoshima, Japan
| | - Makoto Oketani
- Digestive and Lifestyle Diseases, Department of Human and
Environmental Sciences, Kagoshima University Graduate School of Medical and Dental
Sciences, Kagoshima, Japan
| | - Akio Ido
- Digestive and Lifestyle Diseases, Department of Human and
Environmental Sciences, Kagoshima University Graduate School of Medical and Dental
Sciences, Kagoshima, Japan
| | - Katsuhiro Hayashi
- Center for Medical Education, Faculty of Medicine, University of
Miyazaki, Miyazaki, Japan
| | - Kazunori Kusumoto
- Division of Gastroenterology and Hematology, Department of Internal
Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Kazuya Shimoda
- Division of Gastroenterology and Hematology, Department of Internal
Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Sherri O Stuver
- Department of Epidemiology, Boston University School of Public
Health, Boston, MA
| | - Hirohito Tsubouchi
- Digestive and Lifestyle Diseases, Department of Human and
Environmental Sciences, Kagoshima University Graduate School of Medical and Dental
Sciences, Kagoshima, Japan
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Vedham V, Divi RL, Starks VL, Verma M. Multiple infections and cancer: implications in epidemiology. Technol Cancer Res Treat 2013; 13:177-94. [PMID: 23919392 DOI: 10.7785/tcrt.2012.500366] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Approximately 18% of the global cancer burden has been attributed to infectious agents, with estimates ranging from 7% in developed countries to about 22% in developing countries. Chronic infections caused by the hepatitis B and C viruses, human papilloma viruses (HPV), and Helicobacter pylori (H. pylori) are reported to be responsible for approximately 15% of all human cancers. Interestingly, although many of the infectious agents that have been associated with cancer--such as HPV, Epstein-Barr virus (EBV), and H. pylori--are highly prevalent in the world, most infected individuals do not develop cancer but remain lifelong carriers. Malignancies associated with infectious agents may result from prolonged latency as a result of chronic infections. Pathogenic infections are necessary but are not sufficient for cancer initiation or progression. Cancer initiation may require additional cofactors, including secondary infections. Therefore, in patients with chronic infection with one agent, secondary co-infection with another agent may serve as an important co-factor that may cause cancer initiation and progression. Additionally, opportunistic co-infections could significantly inhibit response to cancer treatment and increase cancer mortality. Co-infections are relatively common in areas with a high prevalence of infectious agents, especially in developing countries. These co-infections can cause an imbalance in the host immune system by affecting persistence of and susceptibility to malignant infections. Several articles have been published that focus on infectious agents and cancer. In this article, we discuss the role of infectious agents in malignancies, highlight the role of multiple/co-infections in cancer etiology, and review implications for cancer epidemiology.
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Affiliation(s)
- Vidya Vedham
- Methods and Technologies Branch, Epidemiology and Genomics Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health (NIH), 6130 Executive Boulevard, Suite 5100, Bethesda, MD 20892-7324, USA.
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Nishikawa H, Arimoto A, Wakasa T, Kita R, Kimura T, Osaki Y. Lack of correlation between the antibody to hepatitis B core antigen and survival after surgical resection for hepatitis C virus-related hepatocellular carcinoma. Oncol Rep 2013; 30:91-8. [PMID: 23615658 DOI: 10.3892/or.2013.2422] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2013] [Accepted: 03/16/2013] [Indexed: 11/06/2022] Open
Abstract
The impact of antibodies to hepatitis B core antigen (anti-HBc) on survival after curative surgical resection (SR) for hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) remains unclear. The aim of the present study was to examine the relationship between anti-HBc positivity and survival of HCV-related HCC patients who underwent curative SR. A total of 222 patients with HCV-related, hepatitis B surface antigen (HBsAg)-negative HCC who underwent curative SR were analyzed. They included 119 anti-HBc-positive patients (53.6%) and 103 anti-HBc-negative patients (46.4%). Overall survival (OS) and recurrence-free survival (RFS) rates were compared between the two groups. The median follow-up periods in the anti-HBc-positive and anti-HBc-negative groups were 3.4 years (range, 0.3-10.9 years) and 3.2 years (range, 0.5-10.9 years), respectively. The 1-, 3- and 5-year cumulative OS rates were 88.8, 70.2 and 50.0%, respectively, in the anti-HBc-positive group and 95.8, 77.1 and 61.7% in the anti-HBc-negative group (P=0.300). The corresponding RFS rates were 68.7, 33.0 and 20.0%, respectively, in the anti-HBc-positive group and 74.4, 38.5 and 16.5% in the anti-HBc-negative group (P=0.482). Multivariate analyses identified serum albumin ≥3.8 g/dl (P=0.005) and the presence of microvascular invasion (P<0.001) as independent factors linked to OS, and interferon therapy after surgery (P=0.011), α-fetoprotein ≥40 ng/ml (P=0.030) and the presence of microvascular invasion (P<0.001) were significant predictors linked to RFS. In subgroup analyses according to maximum tumor size and background liver disease in terms of OS and RFS, no significant difference between the anti-HBc-positive and anti-HBc-negative groups was observed except in patients with non-cirrhotic liver in terms of RFS. In conclusion, anti-HBc-positivity is not a useful predictor for survival of patients with HCV-related HCC after curative SR.
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Affiliation(s)
- Hiroki Nishikawa
- Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, Tennoji-ku, Osaka 543-0027, Japan.
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Nishikawa H, Arimoto A, Wakasa T, Kita R, Kimura T, Osaki Y. The Relation between Obesity and Survival after Surgical Resection of Hepatitis C Virus-Related Hepatocellular Carcinoma. Gastroenterol Res Pract 2013; 2013:430438. [PMID: 23710167 PMCID: PMC3655578 DOI: 10.1155/2013/430438] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2013] [Accepted: 04/02/2013] [Indexed: 12/20/2022] Open
Abstract
Background and Aims. We aimed to investigate the relationship between obesity and survival in hepatitis C virus-(HCV-) related hepatocellular carcinoma (HCC) patients who underwent curative surgical resection (SR). Methods. A total of 233 patients with HCV-related HCC who underwent curative SR were included. They included 60 patients (25.8%) with a body mass index (BMI) of > 25 kg/m(2) (obesity group) and 173 patients with a BMI of < 25 kg/m(2) (control group). Overall survival (OS) and recurrence-free survival (RFS) rates were compared. Results. The median follow-up periods were 3.6 years in the obesity group and 3.1 years in the control group. The 1-, 3-, and 5-year cumulative OS rates were 98.3%, 81.0%, and 63.9% in the obesity group and 90.0%, 70.5%, and 50.3% in the control group (P = 0.818). The corresponding RFS rates were 70.1%, 27.0%, and 12.0% in the obesity group and 70.1%, 39.0%, and 21.7% in the control group (P = 0.124). There were no significant differences between the obesity group and the control group in terms of blood loss during surgery (P = 0.899) and surgery-related serious adverse events (P = 0.813). Conclusions. Obesity itself did not affect survival in patients with HCV-related HCC after curative SR.
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Affiliation(s)
- Hiroki Nishikawa
- Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, 5-30 Fudegasaki-cho, Tennoji-ku, Osaka 543-0027, Japan
| | - Akira Arimoto
- Department of Surgery, Osaka Red Cross Hospital, 5-30 Fudegasaki-cho, Tennoji-ku, Osaka 543-0027, Japan
| | - Tomoko Wakasa
- Department of Pathology, Osaka Red Cross Hospital, 5-30 Fudegasaki-cho, Tennoji-ku, Osaka 543-0027, Japan
| | - Ryuichi Kita
- Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, 5-30 Fudegasaki-cho, Tennoji-ku, Osaka 543-0027, Japan
| | - Toru Kimura
- Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, 5-30 Fudegasaki-cho, Tennoji-ku, Osaka 543-0027, Japan
| | - Yukio Osaki
- Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, 5-30 Fudegasaki-cho, Tennoji-ku, Osaka 543-0027, Japan
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13
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Yoshizawa K, Matsumoto A, Ichijo T, Umemura T, Joshita S, Komatsu M, Tanaka N, Tanaka E, Ota M, Katsuyama Y, Kiyosawa K, Abe M, Onji M. Long-term outcome of Japanese patients with type 1 autoimmune hepatitis. Hepatology 2012; 56:668-676. [PMID: 22334246 DOI: 10.1002/hep.25658] [Citation(s) in RCA: 81] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2011] [Accepted: 02/07/2012] [Indexed: 12/18/2022]
Abstract
UNLABELLED The long-term outcome of patients with autoimmune hepatitis (AIH) in Japan has not been well-defined. The aim of this study was to clarify the outcome of this disease over a long follow-up period compared with that of the general Japanese population as well as that among patients. A total of 203 AIH patients were enrolled for a mean follow-up period of 131 months. All patients were treated with corticosteroids with or without azathioprine. The overall survival of AIH patients was similar to that of the general population in Japan. The prognosis of AIH subgroups divided according to disease severity, sex, incidence of relapse, liver histology, presence of cirrhosis, probable or definite AIH score, antibody to hepatitis B core antigen antibody positivity, or human leukocyte antigen DR4-positivity did not differ greatly among patients. However, the prognosis of patients experiencing two or more relapses was significantly poorer than that of patients with remission or a single relapse both in univariate (P < 0.001) and multivariate (P = 0.020) analyses. The development of liver malignancy was also a possibility among AIH patients with multiple relapses. Severe adverse effects of corticosteroids were rare, even in patients who underwent long-term treatment. CONCLUSION Repeated relapses of AIH are significantly associated with a poorer long-term prognosis in Japan. AIH patients can expect a similar prognosis to that of the general population, provided they are adequately managed with continuous low doses of immunosuppressive therapy, especially after the first relapse.
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Affiliation(s)
- Kaname Yoshizawa
- Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
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14
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Japhet MO, Adesina OA, Donbraye E, Adewumi MO. Hepatitis B core IgM antibody (anti-HBcIgM) among hepatitis B surface antigen (HBsAg) negative blood donors in Nigeria. Virol J 2011; 8:513. [PMID: 22074048 PMCID: PMC3239416 DOI: 10.1186/1743-422x-8-513] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2011] [Accepted: 11/10/2011] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Transfusion associated Hepatitis B virus (TAHBV) continues to be a major problem despite mandatory screening for Hepatitis B surface Antigen (HBsAg). Presence of HBsAg is the common method for detecting hepatitis B infection. Unfortunately, this marker is not detected during the window period of the infection. Nigeria being a developing country cannot afford DNA testing of all collected units of blood which serve as the only possibility of achieving zero risk of transfusion associated HBV. Five different serological makers of hepatitis B virus (HBV) infection were therefore assessed to evaluate the reliability of using HBsAg marker alone in diagnosis of HBV infection among blood donors and to detect the serological evidence of the infection at the window period. This will preclude the possibility of transmitting hepatitis B through transfusion of Hepatitis B surface antigen (HBsAg) negative blood in Nigeria. METHODS Between July and August 2009, 92 blood donors were enrolled for the study. The prevalence of 5 different markers of Hepatitis B virus infection was detected using Enzyme Linked Immunosorbent Assay (ELISA). Demographic factors were assessed during the study. RESULTS HBsAg and its antibody (anti-HBs) was detected in 18 (19.6%) and 14(15.2%) of the 92 blood donors respectively. Anti-HBc IgM was found in 12(13.0%) of the 92 blood donors while Hepatitis B envelope antigen (HBeAg) and its antibody (anti-HBe) were detected in 4(8.9%) and 12(26.7%) respectively from 45 donors sampled. HBeAg is a marker of high infectivity and appears after HBsAg. At least one serological marker was detected in 30(32.6%) of the blood donors. Five (5.4%) of the 92 donors had anti-HBc IgM as the only serological evidence of hepatitis B virus infection. CONCLUSIONS The result of this study shows that five donors have anti-HBcIgM as the only serological evidence of HBV infection. Inclusion of anti-HBcIgM in routine screening of blood donors in Nigeria should be encouraged. This is the first study to assess anti-HBcIgM in the country.
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Jain M, Chakravarti A, Kar P. Clinical significance of isolated anti-hbc positivity in cases of chronic liver disease in new delhi, India. J Glob Infect Dis 2011; 1:29-32. [PMID: 20300383 PMCID: PMC2840942 DOI: 10.4103/0974-777x.52978] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
Background: The presence of anti-HBc IgG in the absence of HBsAg is usually indicative of a past self-limiting HBV infection. But it is frequently associated with co-infection with HCV which can worsen the existing status of chronic liver disease (CLD). Objectives: The present study was planned to evaluate the significance of isolated HBc IgG positivity in patients of CLD and look for the presence of HCV co-infection in such patients. Methods: Clinical profiles and biochemical tests were done for all the 77 CLD cases included in the study. Blood samples were taken from these patients and tested by the commercially available EIA for the presence of HBsAg, anti-HBc IgG, anti-HBs and anti-HCV. HBV DNA was detected by amplifying the surface region in all the cases. Results: Isolated anti-HBc IgG positivity defined as the presence of anti-HBc IgG in absence of any other serological markers of HBV infection was detected in 28 patients. Out of 64 patients positive for anti-HBc IgG 36 had the markers of HBV, either HBsAg, HBV DNA or anti-HBs alone or in combination. There was a significant association between isolated anti-HBc IgG positivity and HCV co-infection. Conclusion: Anti-HBc IgG should be tested in all patients with CLD as it is frequently the only marker of HBV infection in such patients and they should be monitored closely as such patients can develop CLD. Presence of co-infection with HCV should be actively searched for in such patients.
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Affiliation(s)
- Manisha Jain
- Department of Microbiology and Maulana Azad Medical College, New Delhi, India
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16
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Nan X, Shi S, Yu C, Zhuang H. Meta-analysis of the association between anti-HBc seropositivity and a poor prognosis of chronic HCV infection. Hepatol Res 2010; 40:1176-87. [PMID: 21040276 DOI: 10.1111/j.1872-034x.2010.00733.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
AIM The impact of serological HBsAg- and anti-HBc+ on the prognosis of chronic hepatitis C virus (HCV) infection is unknown. We conducted a systematic review to analyze whether anti-HBc positivity imposes any effect on the course of HCV-related chronic liver disease. METHODS We retrieved references from online databases that included PubMed and EMBASE. Data were gathered with regard to demographic information, disease progression and prognosis, and the results of serological tests. The development of hepatocellular carcinoma (HCC) was the endpoint of follow-up of all cohort studies. RESULTS Eighteen references were included in this study, of which four were cohort studies. Twelve studies were retrospective, observational and non-interventional studies. According to our meta-analysis, the rate of serological HBsAg- and anti-HBc+ was higher among HCC patients compared with non-HCC patients (odds ratio [OR], 1.55; 95% CI, 1.22-1.98). HCV patients that were anti-HBc+ had a greater chance of developing HCC than their anti-HBc- counterparts (OR, 2.15; 95% CI, 1.34-3.47). CONCLUSIONS The serological status of HBsAg- and anti-HBc+ appears to be correlated with a poor prognosis for chronic HCV infection. Though the general quality of these references was low, and multiple confounding factors existed, the likelihood of a poorer outcome of HCV patients that are positive for anti-HBc should be considered by their physicians.
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Affiliation(s)
- Xiao Nan
- Department of Microbiology Department of Public Health, Peking University Health Science Center, Peking, China
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17
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Chang KC, Tsai PS, Hsu MC, Hung SF, Tsai CC, Lu SN. Chronic hepatitis C increased the mortality rates of patients with hepatocellular carcinoma and diabetes mellitus in a triple hepatitis virus endemic community. J Gastroenterol 2010; 45:636-45. [PMID: 20054698 DOI: 10.1007/s00535-009-0189-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2008] [Accepted: 12/08/2009] [Indexed: 02/06/2023]
Abstract
BACKGROUND To elucidate the factors associated with mortality rates among older subjects with hepatocellular carcinoma (HCC) and diabetes mellitus (DM) in a triple hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis delta virus (HDV) endemic community. METHODS A total of 2,909 residents aged>or=45 years were screened for hepatitis B surface antigen (HBsAg), antibodies to HCV (anti-HCV) and alanine aminotransaminase (ALT) in 1997. Anti-HDV was detected in HBsAg-positive subjects. Those who expired from HCC and DM were identified from official mortality data sets (1997-2003). Survival was analyzed using the Kaplan-Meier survival curve with log-rank test and the Cox proportional hazard model. RESULTS Forty-one patients died of HCC and 25 of DM during the study period. Multivariate analysis indicated that age>or=65 years (hazard ratio 3.4; 95% confidence interval 1.8-6.4), HBsAg (3.3; 1.7-6.7), anti-HCV (3.8; 1.7-8.5) and ALT>or=40 IU/L (3.7; 1.9-7.0) were independent predictors of HCC mortality, while age>or=65 years (4.8; 2.1-11.0) and anti-HCV (4.2; 1.7-10.6) were two independent predictors of DM mortality. There were synergistic effects of dual viral infections for HCC, but not for DM mortality. CONCLUSIONS Old age and chronic HCV infection increase the risk of HCC and DM mortality. HBsAg and ALT levels are also risk factors for HCC mortality, but not DM. The synergistic effects of dual hepatitis viral infections are demonstrable and warrant further investigation.
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Affiliation(s)
- Kuo-Chin Chang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, #123, Ta Pei Road, Niao Sung 833, Kaohsiung, Taiwan
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18
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Prevalence of hepatitis B and C viral markers in chronic liver disease patients: A single center experience from Yemen. Arab J Gastroenterol 2010. [DOI: 10.1016/j.ajg.2010.04.006] [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: 11/23/2022]
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19
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Nasu A, Marusawa H, Ueda Y, Eso Y, Umeda M, Chiba T, Osaki Y, Mawatari H, Kirikoshi H, Inamori M, Saito S, Iwasaki T, Terauchi Y, Kubota K, Maeyama S, Nakajima A. De novo hepatitis B virus infection in hepatocellular carcinoma following eradication of hepatitis C virus by interferon therapy. Hepatol Res 2010; 40:661-5. [PMID: 20618462 DOI: 10.1111/j.1872-034x.2010.00664.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Epidemiological studies have revealed that hepatocellular carcinoma (HCC) is still observed in hepatitis C virus (HCV)-positive patients with a sustained response to interferon (IFN) treatment, although a substantial decrease in the incidence of hepatocellular carcinoma (HCC) has been achieved in those patients. Why HCC develops in patients who have a complete clearance of HCV remains unclear. Here, we provided evidence of latent hepatitis B virus (HBV) infection in an initially HCV-positive chronic hepatitis patient who developed HCC after the complete eradication of HCV by IFN therapy. Although he was initially negative for anti-hepatitis B surface antigen (HBsAg) or circulating HBV DNA but positive for anti-hepatitis B core antigen (anti-HBc) in his sera, he developed HBsAg and HBV DNA during the course of the management of a series of cancers. HBV DNA was detectable in the liver tissues before HBV reactivation and the viral sequences derived from his anti-HBc-positive liver showed 100% homology to that from the serum after HBsAg appearance. These findings indicates that HCV-positive individuals who are positive for anti-HBc in the absence of HBsAg could have latent HBV infection in their liver tissues and intrahepatic HBV infection may play a pivotal role in the development of HCC after the IFN-mediated eradication of HCV.
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Affiliation(s)
- Akihiro Nasu
- Department of Gastroenterology and Hepatology, Kyoto University, Kyoto, Japan
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20
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Ohki T, Tateishi R, Goto E, Sato T, Masuzaki R, Imamura J, Goto T, Kanai F, Kato N, Shiina S, Yoshida H, Kawabe T, Omata M. Influence of anti-HBc seropositivity on the risk of hepatocellular carcinoma in HCV-infected patients after adjusting for confounding factors. J Viral Hepat 2010; 17:91-7. [PMID: 19566786 DOI: 10.1111/j.1365-2893.2009.01152.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
It is controversial whether past hepatitis B virus infection constitutes an additional risk of hepatocellular carcinoma (HCC) among patients with hepatitis C virus (HCV). The incidence of HCC between 1994 and 2004 was analysed among 1262 patients who were only positive for HCV. The cumulative incidence of HCC was assessed by Kaplan-Meier analysis and the difference between two groups was assessed by the log-rank test. The effect of anti-HBc positivity on the risk of HCC was assessed with multivariate Cox proportional analysis. Anti-HBc was positive in 522 (41.4%) patients. The proportion of male patients (56.7 vs 46.8%, P < 0.001) and mean age (60.8 vs 56.9 years, P < 0.001) were significantly higher in the anti-HBc positive group. HCC developed in 339 patients (mean follow-up 7.0 years), with cumulative incidence rates at 3, 5 and 10 years of 12.7, 24.5 and 41.9% in the anti-HBc positive group and 10.6, 17.7 and 33.4% in the negative group, respectively (P = 0.005). However, anti-HBc seropositivity did not reach statistical significance in multivariate analysis including age and gender (hazard ratio, 1.06; 95% CI, 0.85-1.31; P = 0.63). Anti-HBc positivity and HCC incidence were confounded by male gender and older age.
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Affiliation(s)
- T Ohki
- Department of Gastroenterology, University of Tokyo, Bunkyo-ku, Tokyo, Japan
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Loulergue P, Launay O. Vaccinations chez les patients ayant une cirrhose. Presse Med 2009; 38:1134-40. [DOI: 10.1016/j.lpm.2008.11.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2008] [Revised: 11/07/2008] [Accepted: 11/19/2008] [Indexed: 01/07/2023] Open
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Loulergue P, Pol S, Mallet V, Sogni P, Launay O. Why actively promote vaccination in patients with cirrhosis? J Clin Virol 2009; 46:206-9. [PMID: 19501019 DOI: 10.1016/j.jcv.2009.05.006] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2009] [Accepted: 05/01/2009] [Indexed: 02/07/2023]
Abstract
Patients with cirrhosis are immunocompromised and have an increased risk of infection, with a worse outcome. Some of those infections may be prevented by vaccination. Immunization can reduce the morbidity and mortality associated with cirrhosis. Immunizations against hepatitis A and B viruses, influenza and pneumococcus are recommended by the French Haute Autorité de Santé since 2007. Vaccination against hepatitis A is recommended in non-immunized cirrhotic patients. Vaccination against hepatitis B is recommended in every cirrhotic patient with no serological markers, and post-vaccinal antibodies titer should be checked. Annual influenza immunization can be done in cirrhotic patients, and pneumococcal polysaccharide vaccine should be repeated after 3-5 years. Few data regarding vaccination coverage are available, but studies suggest that immunization rates are too low in this population.
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Ikeda K, Kobayashi M, Someya T, Saitoh S, Hosaka T, Akuta N, Suzuki F, Suzuki Y, Arase Y, Kumada H. Occult hepatitis B virus infection increases hepatocellular carcinogenesis by eight times in patients with non-B, non-C liver cirrhosis: a cohort study. J Viral Hepat 2009; 16:437-43. [PMID: 19226331 DOI: 10.1111/j.1365-2893.2009.01085.x] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
An impact of serum hepatitis B virus (HBV) DNA on hepatocarcinogenesis has not been investigated in a cohort of patients with non-B, non-C cirrhosis. Eighty-two consecutive Japanese patients with cirrhosis, who showed negative hepatitis B surface antigen and negative anti-hepatitis C virus, were observed for a median of 5.8 years. Hepatitis B virus core (HBc) region and HBx region were assayed with nested polymerase chain reaction. Both of HBc and HBx DNA were positive in 9 patients (11.0%) and both were negative in 73. Carcinogenesis rates in the whole patients were 13.5% at the end of the 5th year and 24.6% at the 10th year. The carcinogenesis rates in the patients with positive DNA group and negative DNA group were 27.0% and 11.8% at the end of the 5th year, and 100% and 17.6% at the 10th year, respectively (P = 0.0078). Multivariate analysis showed that men (P = 0.04), presence of HBc and HBx DNA (hazard ratio: 8.25, P = 0.003), less total alcohol intake (P = 0.010), older age (P = 0.010), and association of diabetes (P = 0.005) were independently associated with hepatocellular carcinogenesis. Existence of serum HBV DNA predicted a high hepatocellular carcinogenesis rate in a cohort of patients with non-B, non-C cirrhosis.
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Affiliation(s)
- K Ikeda
- Department of Hepatology, Toranomon Hospital, Minato-ku, Tokyo, Japan.
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24
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Tamori A, Hayashi T, Shinzaki M, Kobayashi S, Iwai S, Enomoto M, Morikawa H, Sakaguchi H, Shiomi S, Takemura S, Kubo S, Kawada N. Frequent detection of hepatitis B virus DNA in hepatocellular carcinoma of patients with sustained virologic response for hepatitis C virus. J Med Virol 2009; 81:1009-1014. [PMID: 19382258 DOI: 10.1002/jmv.21488] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Hepatocellular carcinoma (HCC) develops several years after the eradication of hepatitis C virus (HCV) by interferon therapy. Risk factors for the development of HCC are only partly understood. To elucidate the role of occult hepatitis B virus (HBV) infection in hepatocarcinogenesis in patients with sustained virologic response, the prevalences of HBV-related makers were examined. Study group comprised 16 patients with sustained virologic response (group A) and 50 with HCV (group B). Anti-HBc and anti-HBs in serum were examined by enzyme-linked immunoassay. HBV DNA in liver was examined by nested polymerase chain reaction, using primers specific for genes encoding for HBx, HBsAg, HBcAg, and HBV cccDNA. Sequence of the amplified HBV DNA for 'a' determinant of HBsAg was determined in HCC. Anti-HBc was positive in 10 of 16 in group A and 25 of 50 in group B. HBV DNA in liver was detected in 12 of 16 in group A and 21 of 50 in group B (P = 0.044). In group A, HBV DNA in liver was detected frequently in patients without cirrhosis and in those with a longer period from the time of HCV eradication to the development of HCC. Mutation in 'a' determinant of HBsAg was found in three HCC of group A. Occult HBV infection may be one of the most important risk factors in hepatocarcinogenesis of Japanese patients with sustained virologic response.
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Affiliation(s)
- Akihiro Tamori
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan.
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25
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El-Sherif A, Abou-Shady M, Abou-Zeid H, Elwassief A, Elbahrawy A, Ueda Y, Chiba T, Hosney AM. Antibody to hepatitis B core antigen as a screening test for occult hepatitis B virus infection in Egyptian chronic hepatitis C patients. J Gastroenterol 2009; 44:359-364. [PMID: 19271112 DOI: 10.1007/s00535-009-0020-3] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2008] [Accepted: 12/07/2008] [Indexed: 02/06/2023]
Abstract
PURPOSE The presence of hepatitis B virus (HBV) DNA in liver tissue and/or in serum in the absence of detectable hepatitis B surface antigen (HBsAg) is called occult HBV infection. This pattern was identified in patients with chronic hepatitis C virus (HCV) infection. The aim of this study was to determine the role of antibodies to hepatitis B core antigen (anti-HBc) as a screening test for occult HBV infection in Egyptian chronic HCV patients. METHODS One hundred chronic HCV patients negative for HBsAg were included and subdivided into two groups according to anti-HBc-IgG seroreactivity. Group A included 71 patients positive for anti-HBc (53 men and 18 women, mean age +/- SD 48.8 +/- 9.6 years), and group B included 29 patients negative for anti-HBc (18 men and 11 women, mean age +/- SD 46.6 +/- 11.7 years). All patients were subjected to full clinical assessment, routine laboratory investigations, abdominal ultrasonography and quantification of HBV-DNA by real-time PCR. RESULTS Chronic HCV patients positive for anti-HBc have more severe liver disease compared with anti-HBc negative patients. Although HBV-DNA in the serum was detected in 22.5% of anti-HBc-positive chronic HCV patients, it was not detected in any of anti-HBc-negative chronic HCV patients. There was no significant difference in any of the clinical and laboratory data tested between anti-HBc-positive patients with and without HBV-DNA in the serum. CONCLUSION A significant number of patients with anti-HBc had detectable levels of HBV-DNA in the serum. Egyptian chronic HCV patients have a high prevalence of occult HBV infection.
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Affiliation(s)
- Assem El-Sherif
- Department of Internal Medicine, Al-Azhar University, Cairo, Egypt
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Georgiadou SP, Zachou K, Liaskos C, Gabeta S, Rigopoulou EI, Dalekos GN. Occult hepatitis B virus infection in patients with autoimmune liver diseases. Liver Int 2009; 29:434-42. [PMID: 18694399 DOI: 10.1111/j.1478-3231.2008.01851.x] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
BACKGROUND Occult hepatitis B virus (HBV) infection is characterized by undetectable serum HBV surface antigen (HBsAg) but detectable HBV-DNA in serum or liver. AIMS To determine the prevalence and clinical impact of occult HBV in autoimmune liver diseases as similar data are missing. METHODS One hundred and ninety-six sera samples from HBsAg-negative patients, including 66 autoimmune hepatitis (AIH), 93 primary biliary cirrhosis (PBC) and 37 primary sclerosing cholangitis (PSC), were investigated for HBV-DNA using the polymerase chain reaction (PCR) before treatment initiation. One hundred and three serial samples from 38 AIH patients under immunosuppression and 282 selected blood donors (HBsAg negative; antibodies to HBV-core antigen positive) were also investigated. Fourteen available paraffin-embedded AIH liver samples were also investigated for HBV-DNA by nested-PCR. RESULTS Hepatitis B virus DNA was detected in the serum of 24/196 patients (12.2%) and 0/282 donors (P=0.0000). Nine patients had AIH (13.6%), eight had PBC (8.6%) and seven had PSC (18.9%) (P=0.0000 vs healthy). HBV-DNA detection in AIH livers was higher than in serum. HBV-DNA was associated neither with HBV markers nor with epidemiological, laboratory and clinical data. Serial testing of AIH patients revealed two HBV-DNA-negative patients before treatment becoming positive during treatment, while all HBV-DNA-positive patients before immunosuppression became negative. CONCLUSION Based mainly on serum HBV-DNA, we found a significant proportion of autoimmune liver disease patients with occult HBV compared with donors. However, taking into account our results in a small number of liver tissues, it should be emphasized that occult HBV could be even higher when both serum and liver specimens are investigated. Occult HBV does not seem to affect the clinical and laboratory features of the diseases, while AIH patients with occult HBV under immunosuppression do not deteriorate during follow-up.
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Affiliation(s)
- Sarah P Georgiadou
- Department of Medicine, Academic Liver Unit, Research Laboratory of Internal Medicine, Medical School, University of Thessaly, Larissa, Greece
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Carvalho-Filho RJ, de Lucca Schiavon L, Narciso-Schiavon JL, Sampaio JP, Lanzoni VP, Gomes Ferraz ML, Benedito Silva AE. Clinical and histological impact of previous hepatitis B virus infection in patients with chronic hepatitis C. Liver Int 2009; 29:133-140. [PMID: 18507759 DOI: 10.1111/j.1478-3231.2008.01786.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
BACKGROUND Recent reports suggest that hepatitis C virus (HCV) carriers with serological markers of prior hepatitis B virus (HBV) infection have more advanced liver fibrosis, irrespective of HBV-DNA detection. AIMS We sought to assess the prevalence and impact of previous HBV infection in patients with HCV chronic infection. METHODS This cross-sectional study included hepatitis B surface antigen- and human immunodeficiency virus-negative subjects with positive HCV-RNA. All patients had prior parenteral exposure as the probable source of HCV infection. Serum samples were tested for HBV-DNA using a commercial assay. The METAVIR system was used for histological analysis. RESULTS One-hundred and eleven patients were evaluated. Thirty-one out of 111 patients (28%) tested positive for antihepatitis B core antigen (anti-HBc). HBV-DNA was not detected in any sample. Anti-HBc-positive patients showed higher histological grading, staging and a higher fibrosis progression rate. By multivariate analysis, anti-HBc-positivity was predictive of moderate to severe activity [odds ratio (OR)=3.532; P=0.032] and significant hepatic fibrosis (OR=3.364; P=0.017). After approximately 20 years of infection, advanced liver fibrosis (F3/F4) can be expected in 13% of anti-HBc-negative subjects who acquired HCV before the age of 30 and in 57% of those anti-HBc-positive patients who were infected by HCV after 30 years of age (P<0.001). CONCLUSION Previous HBV infection is common among HCV carriers and may exert a negative impact on the natural history of HCV infection, independently of the presence of significant HBV replication.
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Affiliation(s)
- Roberto J Carvalho-Filho
- Division of Gastroenterology, Hepatitis Section, Federal University of Sao Paulo, Sao Paulo, Brazil.
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Adachi S, Shibuya A, Miura Y, Takeuchi A, Nakazawa T, Saigenji K. Impact of occult hepatitis B virus infection and prior hepatitis B virus infection on development of hepatocellular carcinoma in patients with liver cirrhosis due to hepatitis C virus. Scand J Gastroenterol 2008; 43:849-56. [PMID: 18584524 DOI: 10.1080/00365520801935459] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Although hepatitis B virus (HBV) DNA can be detected in liver or sera of patients without serum hepatitis B surface antigen (HBsAg), its clinical relevance in hepatocarcinogenesis remains controversial. This observational cohort study was conducted to clarify the risk factors, including the presence of serum HBV DNA and hepatitis B core antibody (anti-HBc), for hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related liver cirrhosis (LC). MATERIAL AND METHODS The study comprised 123 patients with LC due to HCV, and negative for HBsAg. The risk factors for HCC development were analyzed by univariate and multivariate analysis. Serum samples were assayed for HBV DNA using real-time polymerase chain reaction. RESULTS Serum HBV DNA was detectable in 14 patients (11.4%) and serum anti-HBc in 96 (78.0%). During the follow-up period (mean 53.3 months), 80 patients (65.0%) developed HCC. The cumulative HCC development rate was significantly higher in the anti-HBc-positive group than in the anti-HBc-negative group (p=0.0039), but did not differ between the serum HBV DNA-positive and -negative groups (p=0.8570). The multivariate analysis indicated that male gender, alpha-fetoprotein (AFP) 20 ng/ml or greater, average serum alanine aminotransferase (ALAT) 80 IU/l or greater and the presence of anti-HBc were independent risk factors for development of HCC (p=0.038, p=0.013, p=0.020 and p=0.001, respectively). CONCLUSIONS Serum anti-HBc, which indicates a previous HBV infection, has clinical significance in hepatocarcinogenesis in patients with HCV-related LC, but serum HBV DNA does not. Therefore, anti-HBc in serum is a significant predictor for HCC.
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Affiliation(s)
- Shigeru Adachi
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
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Soejima Y, Shimada M, Taketomi A, Yoshizumi T, Uchiyama H, Ikegami T, Nakamuta M, Maehara Y. Successful living donor liver transplantation using a graft from a hepatitis B surface antigen-positive donor. Liver Int 2007; 27:1282-6. [PMID: 17919241 DOI: 10.1111/j.1478-3231.2007.01528.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
BACKGROUND/AIMS Liver transplantation using a graft from a donor with a positive hepatitis B surface antigen (HBsAg) has been contraindicated owing to the extremely high risk for recurrent disease leading to graft loss. However, the severe shortage of donors often forces the transplant community to utilize suboptimal donors, especially in the setting of living donor liver transplantation (LDLT). METHOD Here, we report a case of successful LDLT for a patient with hepatitis B-related cirrhosis utilizing a graft from an HBsAg-positive 'healthy carrier' donor using a combination prophylaxis of lamivudine and adefovir dipivoxil. RESULTS To date, the patient has been doing well with normal liver function tests and liver histological findings at 4 years after the transplantation and the donor has also been doing well. CONCLUSIONS Although virological recurrence appears to be universal despite prophylaxis, re-evaluation of the use of a graft from a healthy HBsAg-positive donor is warranted in this era of combination prophylaxis.
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Affiliation(s)
- Yuji Soejima
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
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Soejima Y, Ikegami T, Taketomi A, Yoshizumi T, Uchiyama H, Harada N, Yamashita Y, Maehara Y. Hepatitis B vaccination after living donor liver transplantation. Liver Int 2007; 27:977-82. [PMID: 17696937 DOI: 10.1111/j.1478-3231.2007.01521.x] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
BACKGROUND The efficacy of hepatitis B vaccination after living donor liver transplantation (LDLT) in patients transplanted anti-HBc-positive grafts or in patients who underwent LDLT for fulminant hepatitis B remains unknown. METHOD A total of 11 recipients who underwent LDLT between October 1996 and October 2002 prospectively received hepatitis B vaccination three times within 6 months, starting a few weeks after the cessation of hepatitis B immunoglobulin (HBIG) prophylaxis. Serial quantification of the hepatitis B surface antibody (HBsAb) was performed. RESULTS At the last follow-up, six out of 11 patients (54.5%) had seroconversion and were free from HBIG thereafter. Four out of those six responders had a peak HBsAb level of more than 1000 IU/L, while the other two patients had peak HbsAb levels below 1000 IU/L. Five patients never responded to the treatment and were back to HBIG prophylaxis. The average age of the six responders was 25.5 years, which was significantly younger than that of non-responders (44.4 years, P<0.05). None had side effects or hepatitis B infection during the study period. CONCLUSIONS In conclusion, the use of this treatment modality could be used to reduce the cost of HBIG.
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Affiliation(s)
- Yuji Soejima
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
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Hatanaka K, Kudo M, Fukunaga T, Ueshima K, Chung H, Minami Y, Sakaguchi Y, Hagiwara S, Orino A, Osaki Y. Clinical characteristics of NonBNonC- HCC: Comparison with HBV and HCV related HCC. Intervirology 2006; 50:24-31. [PMID: 17164554 DOI: 10.1159/000096309] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2005] [Accepted: 01/10/2006] [Indexed: 01/03/2023] Open
Abstract
OBJECTIVE To clarify the frequency and trends of both HBsAg and HCVAb negative hepatocellular carcinoma (NonBNonC-HCC) in all HCC, to clarify the etiology of NonBNonC-HCC, and to elucidate the clinical characteristics of NonBNonC-HCC compared with those of HBsAg-positive HCC (B-HCC) and HCVAb-positive HCC (C-HCC). METHODS A total of 2,542 patients with HCC examined at three institutions between 1991 and 2004 were categorized based on their serum viral antigen/antibody positivities, and compared between groups for the etiology, annual trend of the incidence, and clinical characteristics. RESULTS For the etiology, C-HCC was most prevalent, followed by B-HCC, NonBNonC-HCC, and both HBsAg and HCVAb-positive HCC (BC-HCC) in order. For survival, C-HCC had the most favorable prognosis, followed by NonBNonC-HCC, and B-HCC patients had the poorest prognosis in the three groups (C-HCC, B-HCC, and NonBNonC-HCC). In tumor-node metastasis (TNM) stages I+II, however, NonBNonC-HCC patients took the most favorable clinical course. The incidence of NonBNonC-HCC in all HCC was 5-8% from 1991 to 1998, and has increased to 10-12% since 1999. Additionally, the incidence of HBcAb-positive HCC in NonBNonC-HCC declined each year. Among NonBNonC-HCC patients, the morbidity of diabetic complications was significantly higher in HBcAb-negative patients than in HBcAb-positive patients. CONCLUSION Although the incidence of NonBNonC-HCC among all HCC has an increasing trend recently, the incidence of HBcAb-positive HCC in NonBNonC-HCC has a tendency of decreasing. This fact suggest its etiology might be changing from occult HBV related HCC to unknown etiology such as nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) related HCC. The prognosis of NonBNonC-HCC was fairly good if the HCC was found in its early stage.
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Affiliation(s)
- Kinuyo Hatanaka
- Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Osaka, Japan
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MUELLER NANCYE, BIRMANN BRENDAM, PARSONNET JULIE, SCHIFFMAN MARKH, STUVER SHERRIO. Infectious Agents. CANCER EPIDEMIOLOGY AND PREVENTION 2006:507-548. [DOI: 10.1093/acprof:oso/9780195149616.003.0026] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
AbstractThere is substantial evidence that infectious agents play a causal role in a variety of human malignancies. These cancers include the liver, cervix, stomach, nasopharynx, bladder, and bile duct as well as Kaposi sarcoma (KS) and several lymphomas. This chapter summarizes the biological and epidemiologic features of each of the major oncogenic infections, beginning with the viruses, followed by H. pylori, and with a brief summary of the relevant parasites.
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Liu Z, Hou J. Hepatitis B virus (HBV) and hepatitis C virus (HCV) dual infection. Int J Med Sci 2006; 3:57-62. [PMID: 16614744 PMCID: PMC1415845 DOI: 10.7150/ijms.3.57] [Citation(s) in RCA: 55] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2005] [Accepted: 03/15/2006] [Indexed: 12/22/2022] Open
Abstract
Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections account for a substantial proportion of liver diseases worldwide. Because the two hepatotropic viruses share same modes of transmission, coinfection with the two viruses is not uncommon, especially in areas with a high prevalence of HBV infection and among people at high risk for parenteral infection. Patients with dual HBV and HCV infection have more severe liver disease, and are at an increased risk for progression to hepatocellular carcinoma (HCC). Treatment of viral hepatitis due to dual HBV/HCV infection represents a challenge.
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Umeda M, Marusawa H, Seno H, Katsurada A, Nabeshima M, Egawa H, Uemoto S, Inomata Y, Tanaka K, Chiba T. Hepatitis B virus infection in lymphatic tissues in inactive hepatitis B carriers. J Hepatol 2005; 42:806-12. [PMID: 15885350 DOI: 10.1016/j.jhep.2005.01.016] [Citation(s) in RCA: 54] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2004] [Revised: 01/11/2005] [Accepted: 01/27/2005] [Indexed: 12/13/2022]
Abstract
BACKGROUND/AIMS Hepatitis B virus (HBV) infection in extrahepatic tissues is controversial. To clarify whether episomal HBV can infect nonhepatic tissues, we investigated the molecular forms of HBV in the lymphatic cells of inactive HBV carriers who lacked viremia, thus avoiding contamination with HBV genomes originating from the viral particles present in the serum. METHODS We assessed HBV genome, replicative forms, and viral integrants in the liver, serum, peripheral blood mononuclear cells (PBMC), and lymph nodes of 21 inactive HBV carriers who tested positive for antibodies against the HBV core antigen (anti-HBc). RESULTS Of the 21 anti-HBc positive individuals, HBV-DNA was detected in liver samples of 15 (71.4%), in the lymph nodes of 11 (52.4%), and in PBMC of three (14.3%). However, none of the detected HBV genomes from lymphatic tissues included the replicative forms of HBV. In one case, integrated HBV was present in the lymphatic tissues and the host-viral junction was present in the intronic sequences of chromosome 17. CONCLUSIONS These data suggest that human lymphatic tissues cannot support viral replication in anti-HBc positive inactive HBV carriers, while retaining the viral genome as an integrated form.
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Affiliation(s)
- Makoto Umeda
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Kawara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
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35
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Tanaka H, Iwasaki Y, Nouso K, Kobayashi Y, Nakamura SI, Matsumoto E, Toshikuni N, Kaneyoshi T, Ohsawa T, Takaguchi K, Fujio K, Senoh T, Ohnishi T, Sakaguchi K, Shiratori Y. Possible contribution of prior hepatitis B virus infection to the development of hepatocellular carcinoma. J Gastroenterol Hepatol 2005; 20:850-856. [PMID: 15946131 DOI: 10.1111/j.1440-1746.2005.03823.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
BACKGROUND The prevalence of prior hepatitis B virus (HBV) infection in hepatocellular carcinoma (HCC) patients and its role in hepatocarcinogenesis are not clear. The aim of the present study is to clarify the importance of prior HBV infection in development of HCC. METHODS Of 1288 consecutive HCC patients between January 1999 and October 2002, 1008 patients were enrolled. To determine the influence of prior HBV infection in hepatitis B surface antigen (HBsAg)-negative HCC, the prevalence of antibody to hepatitis B core antigen (anti-HBc) was examined according to age, and the clinical features were compared between the anti-HBc positive and the negative groups. RESULTS The proportion of HBsAg-negative HCC patients, HCC patients with antibody to hepatitis C virus (anti-HCV; C-HCC) and HCC patients negative for both HBsAg and anti-HCV (nBnC-HCC), increased with age. The anti-HBc-positive rates in C-HCC patients also increased with age. Those rates in nBnC-HCC patients were >50% in all age groups. Furthermore, it was found that the anti-HBc-positive rates of these patients were higher than those of corresponding control patients. Tumor size and a positive rate for vessel involvement both in C-HCC and nBnC-HCC patients were larger and higher, respectively, in anti-HBc-positive patients compared with anti-HBc-negative patients, although the difference in nBnC-HCC did not reach statistical significance because of the small numbers. These tumor characteristics were similar to those of B-HCC patients. CONCLUSION A possible contribution of prior HBV infection to the development of HCC is indicated.
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Affiliation(s)
- Hironori Tanaka
- Department of Gastroenterology, Hepatology and Infectious Disease, Okayama University School of Medicine, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
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Michielsen PP, Francque SM, van Dongen JL. Viral hepatitis and hepatocellular carcinoma. World J Surg Oncol 2005; 3:27. [PMID: 15907199 PMCID: PMC1166580 DOI: 10.1186/1477-7819-3-27] [Citation(s) in RCA: 102] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2004] [Accepted: 05/20/2005] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. The incidence of HCC varies considerably with the geographic area because of differences in the major causative factors. Chronic hepatitis B and C, mostly in the cirrhotic stage, are responsible for the great majority of cases of HCC worldwide. The geographic areas at the highest risk are South-East Asia and sub-Saharan Africa, here hepatitis B is highly endemic and is the main cause of HCC. In areas with an intermediate rate of HCC such as Southern Europe and Japan, hepatitis C is the predominant cause, whereas in low rate areas such as Northern Europe and the USA, HCC is often related to other factors as alcoholic liver disease. There is a rising incidence in HCC in developed countries during the last two decades, due to the increasing rate of hepatitis C infection and improvement of the clinical management of cirrhosis. METHODS This article reviews the literature on hepatitis and hepatocellular carcinoma. The Medline search was carried out using these key words and articles were selected on epidemiology, risk factors, screening, and prevention of hepatocellular carcinoma. RESULTS Screening of patients with advanced chronic hepatitis B and C with hepatic ultrasound and determination of serum alfa-fetoprotein may improve the detection of HCC, but further studies are needed whether screening improves clinical outcome. Hepatitis B and C viruses (HBV/HCV) can be implicated in the development of HCC in an indirect way, through induction of chronic inflammation, or directly by means of viral proteins or, in the case of HBV, by creation of mutations by integration into the genome of the hepatocyte. CONCLUSION The most effective tool to prevent HCC is avoidance of the risk factors such as viral infection. For HBV, a very effective vaccine is available. Preliminary data from Taiwan indicate a protective effect of universal vaccination on the development of HCC. Vaccination against HBV should therefore be a health priority. In patients with chronic hepatitis B or C, interferon-alfa treatment in a noncirrhotic stage is protective for HCC development in responders, probably by prevention of cirrhosis development. When cirrhosis is already present, the protective effect is less clear. For cirrhosis due to hepatitis B, a protective effect was demonstrated in Oriental, but not in European patients. For cirrhosis due to hepatitis C, interferon-alfa treatment showed to be protective in some studies, especially in Japan with a high incidence of HCC in untreated patients. Virological, but also merely biochemical response, seems to be associated with a lower risk of development of HCC. As most studies are not randomized controlled trials, no definitive conclusions on the long-term effects of interferon-alfa in HBV or HCV cirrhosis can be established. Especially in hepatitis C, prospective studies should be performed using the more potent reference treatments for cirrhotics, namely the combination of peginterferon and ribavirin.
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Affiliation(s)
- Peter P Michielsen
- Division of Gastroenterology and Hepatology University Hospital Antwerp, Belgium
| | - Sven M Francque
- Division of Gastroenterology and Hepatology University Hospital Antwerp, Belgium
| | - Jurgen L van Dongen
- Division of Gastroenterology and Hepatology University Hospital Antwerp, Belgium
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Tokita H, Fukui H, Tanaka A, Kamitsukasa H, Yagura M, Harada H, Okamoto H. Risk factors for the development of hepatocellular carcinoma among patients with chronic hepatitis C who achieved a sustained virological response to interferon therapy. J Gastroenterol Hepatol 2005; 20:752-8. [PMID: 15853990 DOI: 10.1111/j.1440-1746.2005.03800.x] [Citation(s) in RCA: 76] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM Hepatitis C virus (HCV)-infected patients who responded to interferon (IFN) treatment with clearance of serum HCV RNA may rarely develop hepatocellular carcinoma (HCC). The aim of the present study was to elucidate the risk factors for liver carcinogenesis among such patients. METHODS In total, 126 patients with chronic hepatitis C (CHC) who achieved a sustained virological response (SVR) to IFN monotherapy, which was defined as the absence of detectable HCV RNA in the serum at 6 months after completion of treatment, were enrolled and possible risk factors for HCC were analyzed. RESULTS During the observation period of 66 +/- 36 months after cessation of IFN treatment, five (4.0%) of the 126 patients developed HCC. The cumulative incidence of HCC at 3, 5 and 10 years was estimated to be 0.9, 4.7 and 7.5%, respectively. The cumulative incidence of HCC was significantly higher among patients with severe fibrosis (F3 or F4) than among patients with no or mild fibrosis (F0 to F2) in the liver before treatment (P = 0.007); among patients with alcohol intake of > or = 27 g/day than among patients with that of < 27 g/day (P = 0.015); and among patients who were > or = 65 years old than among patients who were < 65 years old at the start of treatment (P = 0.026). CONCLUSIONS Patients with CHC who had severe fibrosis, who had regularly taken moderate amounts of alcohol, or who were > or = 65 years at the start of IFN treatment should be carefully followed to detect small and controllable HCC, even after eradication of HCV.
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Affiliation(s)
- Hajime Tokita
- Department of Gastroenterology, National Tokyo Hospital, Tokyo, Japan
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Chlabicz S, Lapinski TW, Grzeszczuk A, Prokopowicz D. Four-year follow up of hepatitis C patients vaccinated against hepatitis B virus. World J Gastroenterol 2005; 11:1798-801. [PMID: 15793867 PMCID: PMC4305877 DOI: 10.3748/wjg.v11.i12.1798] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: Patients with chronic hepatitis C have been recommended to receive vaccinations against hepatitis B. Our study aimed at evaluating the hepatitis B immunogenicity and efficacy against hepatitis B virus infection 4 years after primary immunization series in a group of patients with chronic hepatitis C.
METHODS: We recruited 36 out of 48 hepatitis C virus (HCV) infected individuals who were vaccinated against hepatitis B virus (20 μg of recombinant HBsAg at 0-1-6 mo schedule) in 1998. Here we measured anti-HBs titers and anti-HBc 4 years after delivery of the third dose of primary immunization series.
RESULTS: After 4 years a total of 13/36 (36%) HCV infected patients had seroprotective titers of anti-HBs compared with 9/10 (90%) in the control group, (P<0.05). Similarly the mean concentration of anti-HBs found in hepatitis C patients was significantly lower than that found in healthy subjects (18.3 and 156.0 mIU/mL respectively (P<0.05). None of the HCV infected patients or controls became infected with HBV during the study period as confirmed by anti-HBc negativity.
CONCLUSION: We demonstrated that 4 years after HBV immunizations’ more than 60% of vaccinated HCV patients did not maintain seroprotective levels of anti-HBs, which might put them at risk of clinically significant breakthrough infections. Further follow-up studies are required to clarify whether memory B and T lymphocytes can provide protection in chronic hepatitis C patients in the absence or inadequate titers of anti-HBs.
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Abstract
BACKGROUND AND AIM To estimate the risk of hepatocellular carcinoma (HCC) in non-alcoholic patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, 118 patients who were admitted to a regional hospital in Saudi Arabia were compared with 118 age- and sex-matched healthy individuals. RESULTS The prevalence of HBsAg in HCC patients (67%; 95% confidence interval (CI): 57.7-75.3) was significantly higher than the rate (6.7%; 95%CI: 3.0-12.9) in the controls (OR: 28.4; 95%CI: 12.6-63.9; P < 0.001). There was a high risk of HCC in the presence of HBsAg alone (OR: 34.3; 95%CI: 14.8-79.1, P < 0.001) and anti-HCV alone (OR: 12.2; 95%CI: 3.2-47.2; P < 0.001). Although HBV and HCV were independent risk factors in the development of HCC, there was no interactive relationship between the two viruses. Dual infections occurred in only 3.4% and were associated with only a moderate increase in the risk of HCC (OR: 14.6; 95%CI: 1.57-135.9). In 24.6% of the cases no virus was identified as the etiologic factor. CONCLUSION Hepatitis B virus constitutes a major risk factor and HCV contributes a less significant role in the development of HCC. The ongoing program of HBV vaccination may significantly decrease the prevalence of HBV-associated HCC in this population.
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Affiliation(s)
- Ephraim A Ayoola
- Department of Medicine, King Fahd Central Hospital, Gizan, Saudi Arabia.
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Xu B, Hu DC, Rosenberg DM, Jiang QW, Lin XM, Lu JL, Robinson NJ. Chronic hepatitis B: a long-term retrospective cohort study of disease progression in Shanghai, China. J Gastroenterol Hepatol 2003; 18:1345-52. [PMID: 14675261 DOI: 10.1046/j.1440-1746.2003.03187.x] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
BACKGROUND AND AIMS The present study aimed to describe the disease progression of chronic hepatitis B patients without or with compensated cirrhosis at baseline, to estimate the risk of progression to decompensated cirrhosis, hepatocellular carcinoma and death, and to determine prognostic factors of disease progression in patients in Shanghai, China. METHODS Stored medical records from 322 biopsy-confirmed chronic hepatitis B cases diagnosed between 1981 and 1993 were selected, and the status of patients was tracked in 1999-2000. Among consenting patients, ultrasound examination and laboratory tests were conducted. Person-year incidence rates, Kaplan-Meier analysis, log-rank tests, and Cox regression analysis were conducted. RESULTS Among chronic hepatitis B patients without compensated cirrhosis, the incidence rates of decompensated cirrhosis, hepatocellular carcinoma, and death were 6.3, 2.8, and 7.6 per 1000 person-years, respectively, while for patients with compensated cirrhosis, the rates were 35.6, 8.2, and 35.2 per 1000 person-years, respectively. The 15-year survival rate was 88% for patients without compensated cirrhosis, compared with 56% for patients with compensated cirrhosis (P < 0.001). Cox regression analysis demonstrated that increased alpha-fetoprotein (AFP) (P < 0.01), gamma-globulin (P < 0.05), and high-level severity of hepatic fibrosis (P < 0.01) at baseline were risk factors of decompensated cirrhosis. Factors associated with a high risk of death included elevated AFP at baseline (P < 0.01), severity of hepatic fibrosis (P < 0.003), and sustained positivity for hepatitis B surface antigen (P < 0.004). CONCLUSION Increased AFP and severity of hepatic fibrosis at baseline were associated with higher risk of decompensated cirrhosis and death. These data provide rare empirical estimates of the negative long-term outcomes for patients with chronic hepatitis B in Shanghai, China.
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Affiliation(s)
- Biao Xu
- Department of Epidemiology, School of Public Health, Singapore.
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41
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Tamori A, Nishiguchi S, Kubo S, Narimatsu T, Habu D, Takeda T, Hirohashi K, Shiomi S. HBV DNA integration and HBV-transcript expression in non-B, non-C hepatocellular carcinoma in Japan. J Med Virol 2003; 71:492-498. [PMID: 14556260 DOI: 10.1002/jmv.10514] [Citation(s) in RCA: 39] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Few studies have examined the etiology of hepatocellular carcinoma (HCC) in patients without hepatitis virus infection. We evaluated the role of occult hepatitis B virus (HBV) infection in the development of HCC in Japanese patients without hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C antigen (anti-HCV). Twenty-one HBsAg negative and anti-HCV negative (non-B, non-C) patients with HCC were studied. HBV DNA in serum and HBV transcripts in liver were examined by polymerase chain reaction (PCR) or reverse transcription and PCR. HBV DNA integration was examined by Southern blot analysis or cassette-ligation-mediated PCR as described previously. p53 mutations were examined by direct sequencing. HBV DNA was not detected in serum from any patients. HBV-related transcripts were detected in 5 of 7 HCCs from patients with antibodies to hepatitis core antigen (anti-HBc) and in 3 of 14 HCCs from patients without anti-HBc (P = 0.0261). HBV DNA was integrated into human genome in two non-B, non-C HCCs. Of the 14 patients without anti-HBc, 5 had a history of excessive alcohol intake. In exons 5 through 8 of the p53 gene, mutations were detected in 2 of 8 HCCs with HBV-transcripts and in 5 of 13 HCCs without such transcripts. p53 mutation at codon 159 was found in 2 of 6 patients with excessive alcohol intake without HBV-transcripts. These results suggested that occult HBV infection might play an important role in hepatocarcinogenesis in non-B, non-C patients with anti-HBc and that excessive alcohol intake might be related to HCC in non-B, non-C patients in Japan.
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MESH Headings
- Adult
- Aged
- Base Sequence
- Carcinoma, Hepatocellular/etiology
- Carcinoma, Hepatocellular/virology
- DNA, Viral/genetics
- DNA, Viral/isolation & purification
- Female
- Genes, p53
- Hepatitis B/complications
- Hepatitis B/virology
- Hepatitis B Antibodies/blood
- Hepatitis B Surface Antigens/blood
- Hepatitis B virus/genetics
- Hepatitis B virus/isolation & purification
- Hepatitis B virus/pathogenicity
- Hepatitis C Antibodies/blood
- Humans
- Japan
- Liver Neoplasms/etiology
- Liver Neoplasms/virology
- Male
- Middle Aged
- Molecular Sequence Data
- Mutation
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- RNA, Viral/genetics
- RNA, Viral/metabolism
- Transcription, Genetic
- Virus Integration/genetics
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Affiliation(s)
- Akihiro Tamori
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan.
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42
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Casato M, Lilli D, Donato G, Granata M, Conti V, Del Giudice G, Rivanera D, Scagnolari C, Antonelli G, Fiorilli M. Occult hepatitis C virus infection in type II mixed cryoglobulinaemia. J Viral Hepat 2003; 10:455-9. [PMID: 14633180 DOI: 10.1046/j.1365-2893.2003.00462.x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
Mixed cryoglobulinaemia, when not secondary to other well-defined immunological disorders, is commonly associated with hepatitis C virus (HCV) infection. However, a minority of cases lack evidence of HCV infection and are, therefore, defined as 'true essential' mixed cryoglobulinaemias. We thoroughly investigated three such patients to determine the aetiology of this disorder. Antibodies to HCV (anti-HCV) and HCV RNA, detected by sensitive enzyme-linked immunosorbent and polymerase chain reaction assays in serum and in concentrated cryoglobulins, were repeatedly negative in the three patients. Despite the lack of evidence for HCV infection, two of them were still treated with interferon alpha-2a assuming unrecognized viral infection. Both patients demonstrated excellent clinical and laboratory responses, but cryoglobulinaemia relapsed after the withdrawal of therapy. At the time of relapse, HCV RNA genomic sequences were detected for the first time in the cryoprecipitates of both patients. In the third case, HCV RNA was demonstrated for the first time during a flare of cryoglobulinaemia coincident with varicella infection. In all three patients anti-HCV antibodies remained negative throughout follow-up. We conclude that some apparently 'essential' forms of mixed cryoglobulinaemia can be caused by occult HCV infection. Interferon therapy can be taken into consideration in such HCV-negative cases.
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Affiliation(s)
- M Casato
- Department of Clinical Medicine, University of Rome La Sapienza, Rome, Italy
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43
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Wang KX, Peng JL, Wang XF, Tian Y, Wang J, Li CP. Detection of T lymphocyte subsets and mIL-2R on surface of PBMC in patients with hepatitis B. World J Gastroenterol 2003; 9:2017-20. [PMID: 12970897 PMCID: PMC4656665 DOI: 10.3748/wjg.v9.i9.2017] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the levels of T lymphocyte subsets and membrane interleukin-2 receptor (mIL-2R) on surface of peripheral blood mononuclear cells (PBMCs) of patients with hepatitis B and its role in the pathogenesis of hepatitis B.
METHODS: The levels of T lymphocyte subsets and mIL-2R in PBMC before and after being stimulated with PHA were detected by biotin-streptavidin (BSA) technique in 196 cases of hepatitis B.
RESULTS: In patients with hepatitis B, the levels of CD3+, CD4+ cells, and the ratio of CD4+ cells/CD8+ cells were lower, but the level of CD8+ cells was higher than those in normal controls (42.20 ± 6.01 vs 65.96 ± 6.54, 38.17 ± 5.93 vs 41.73 ± 6.40, 0.91 ± 0.28 vs 1.44 ± 0.31, 39.86 ± 6.36 vs 30.02 ± 4.54, P < 0.01). The total expression level of mIL-2R in PBMC before and after being stimulated with PHA was also lower than those in normal controls (3.47 ± 1.55 vs 4.52 ± 1.49, 34.03 ± 2.94 vs 37.95 ± 3.00, P < 0.01). In all the patients with hepatitis B, the levels of T lymphocyte subsets and mIL-2R in PBMC with HBV-DNA (+) were lower than those with HBV-DNA (-), which were significantly different (39.57 ± 7.11 vs 44.36 ± 5.43, 34.36 ± 7.16 vs 40.75 ± 5.87, 37.82 ± 6.54 vs 41.72 ± 6.21, 0.88 ± 0.33 vs 0.99 ± 0.27, 2.82 ± 1.62 vs 3.85 ± 1.47, 31.56 ± 3.00 vs 35.84 ± 2.83, P < 0.01). In addition, the levels of CD3+, CD4+, CD8+ cells, the ratio of CD4+ cells/CD8+ cells and mIL-2R among different courses of hepatitis B were all significantly different (F = 3723.18, P < 0.01. F = 130.43, P < 0.01. F = 54.01, P < 0.01. F = 2.99, P < 0.05. F = 7.16, P < 0.01).
CONCLUSION: Both cellular and humoral immune functions are obviously in disorder in patients with hepatitis B, which might be closely associated with the chronicity in patients.
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Affiliation(s)
- Ke-Xia Wang
- School of Medicine, Anhui University of Science and Technology, Huainan 232001, Anhui Province, China
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44
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Yano Y, Yamashita F, Sumie S, Kuwaki K, Yamamoto H, Toyoda N, Ando E, Tanaka M, Sata M. Clinical significance of antibody against hepatitis B virus core antigen in patients with hepatitis C virus-related hepatocellular carcinoma. Liver Int 2003; 23:227-31. [PMID: 12895261 DOI: 10.1034/j.1600-0676.2003.00831.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
PURPOSE We investigated the unsettled issue of whether seropositivity for antibody to hepatitis B core antigen (anti-HBc) affects characteristics of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). METHODS Antibody status was determined by enzyme immunoassay in 243 patients with this cancer, and associations with clinicopathologic characteristics and outcome were analysed. Serum hepatitis B virus (HBV) DNA was determined by real-time polymerase chain reaction. RESULTS Of 235 patients with unequivocal serologic status, 142 were seropositive and 93 were seronegative. Clinicopathologic characteristics and overall cumulative survival rates were comparable between the two groups. However, seropositivity tended to predict poor outcome for patients in Child class B or C (P=0.068), those in tumour-nodes-metastasis-based stage 3 or 4 (P=0.081), those with tumours exceeding 25 mm (P=0.068), and those with a past history of clinical liver disease (P=0.088). Multivariate analysis identified serum albumin, portal vein tumour thrombosis, and tumour size as independent determinants of survival. Serum HBV DNA was below 1.7 log copies/ml in all 40 patients tested. CONCLUSIONS Overall, the clinical features of HCV-HCC were unaffected by seropositivity for anti-HBc. Seropositivity tended to worsen prognosis for subgroup with poor hepatic reserve or advanced tumours.
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Affiliation(s)
- Yoichi Yano
- Department of Medicine, Saga Social Insurance Hospital, Saga-City, Japan
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45
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Kaplan DE, Reddy KR. Rising incidence of hepatocellular carcinoma: the role of hepatitis B and C; the impact on transplantation and outcomes. Clin Liver Dis 2003; 7:683-714. [PMID: 14509534 DOI: 10.1016/s1089-3261(03)00060-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma caused by hepatitis B and hepatitis C are global scourges but are likely to peak in incidence in the next 2 decades and then decline. Universal vaccination has been effective in stemming the incidence of chronic hepatitis B and early-onset HCC in regions of high endemicity where implemented, but preventive measures in HCV are not yet available. After the attrition of older affected generations, the incidence of HCC will likely decline rapidly. While no vaccine is currently available for hepatitis C, cases are projected to peak and decline because of a marked reduction in transmission as a result of behavioral modification and safeguarding of blood supplies. Until these epidemiologic projections come to pass, management of hepatocellular carcinoma will continue to become a progressively more frequently encountered clinical challenge. Therapy for chronic hepatitis may ameliorate but will not eliminate the development of tumors. The demand for orthotopic liver transplantation will continue to climb, and palliative therapies for non-resectable cases will require studies aimed at optimization of benefit. LDLT may remain an option for high-risk patients affording tumor-free survival for some otherwise terminal patients.
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Affiliation(s)
- David E Kaplan
- Division of Gastroenterology and Hepatology, University of Pennsylvania School of Medicine, 3 Raydin, 3400 Spruce Street, Philadelphia, PA 19104, USA
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46
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Santagostino E, Colombo M, Rivi M, Rumi MG, Rocino A, Linari S, Mannucci PM. A 6-month versus a 12-month surveillance for hepatocellular carcinoma in 559 hemophiliacs infected with the hepatitis C virus. Blood 2003; 102:78-82. [PMID: 12649165 DOI: 10.1182/blood-2002-10-3310] [Citation(s) in RCA: 84] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is an increasingly frequent cause of mortality in hemophiliacs with chronic viral hepatitis. Early diagnosis of the tumor at an initial stage is known to improve the outcome of HCC treatment. Because all HCC cases detected in a previous study based upon annual ultrasound (US) surveillance of hemophiliacs with elevated alanine aminotransferase levels were multinodular, this study was designed to evaluate if a more intense surveillance with US and alphafetoprotein (AFP) serum levels of all the patients infected with the hepatitis C virus (HCV) improved the identification of single nodule tumors. A multicenter cohort of 559 HCV-infected hemophiliacs was divided into 2 arms, one followed up at 6-month intervals and one at 12-month intervals depending on the choice and available facilities of each treatment center. During a 6-year surveillance period, HCC was diagnosed in 5 (2.4%) of 210 patients in the 6-month group and in 3 (0.9%) of 349 patients in the 12-month group. The overall incidence rate of HCC was 239 per 100 000 per year (397 per 100 000 per year in the 6-month group and 143 per 100 000 per year in the 12-month group; differences not statistically significant). By multivariate analysis, HCC risk was increased 12.9-fold with alcohol intake more than 80 g/d and 15.2-fold with AFP levels higher than 11 ng/mL. Liver-related death occurred in 8 cases (1.4%), including 3 with HCC. Still alive and tumor free after 24 to 34 months from diagnosis are 3 patients with multinodular tumors treated with repeat chemoembolization followed by orthotopic liver transplantation. In conclusion, 6-month surveillance with US did not increase the chances of detection of single nodule tumors, but it is reasonable to assume that successful treatment of multinodular tumors based upon debulking with chemoembolization and liver transplantation was facilitated by this approach.
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Affiliation(s)
- Elena Santagostino
- Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Internal Medicine, Division of Hepatology, IRCCS Maggiore Hospital, University of Milan, Via Pace 9, 20122 Milan, Italy
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47
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Tamori A, Nishiguchi S, Kubo S, Enomoto M, Koh N, Takeda T, Shiomi S, Hirohashi K, Kinoshita H, Otani S. Sequencing of human-viral DNA junctions in hepatocellular carcinoma from patients with HCV and occult HBV infection. J Med Virol 2003; 69:475-481. [PMID: 12601754 DOI: 10.1002/jmv.10334] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
DNA of free hepatitis B viruses (HBV) has been detected in the liver of patients infected with hepatitis C virus (HCV). It is unknown whether HBV DNA is integrated into such livers; if so, it may affect hepatocarcinogenesis. Hepatocellular carcinomas (HCCs) from 34 patients without HBV surface antigen (HBsAg) and with anti-HCV, and from 7 patients with HBsAg and without anti-HCV as controls, were examined, using the cassette-ligation-mediated polymerase chain reaction and primers based on HBV DNA sequence. In the controls, HBV DNA had been integrated into human DNA of all HCCs. On the basis of HBV DNA in tumor tissue, 23 of the 34 patients with anti-HCV had occult infection. Junctions between human DNA and HBV DNA were detected in 10 of the 34 patients without HBsAg and with anti-HCV. HBV DNA was integrated into chromosome 11q in 4 of the 10 HCCs with junctions. The DNA to either side of the human-viral junctions was sequenced. Clinically, the mean tumor size of these 10 HCCs was 39 mm; that of the 24 HCCs without integrated HBV was 25 mm. The surrounding tissue was cirrhotic in 2 of the 10 former HCCs and in 16 of the latter 24 HCCs. In conclusion, integrated HBV was detected in some patients with HCV infection; in these patients, the integrated DNA was associated with accelerated hepatocarcinogenesis.
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Affiliation(s)
- Akihiro Tamori
- Department of Hepatology, Osaka City University Graduate School of Medicine, Japan
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48
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Abstract
Occult hepatitis B virus (HBV) infection is characterized by presence of HBV infection with undetectable hepatitis B surface antigen (HBsAg). Serum HBV level is usually less than 104 copies/mL in these patients. Diagnosis of occult HBV infection requires sensitive HBV-DNA PCR assay. Several possibilities have been hypothesized as the mechanisms of occult HBV infection. These include: (i) mutations of HBV-DNA sequence; (ii) integration of HBV-DNA into host's chromosomes; (iii) infection of peripheral blood mononuclear cells by HBV; (iv) formation of HBV-containing immune complex; (v) altered host immune response; and (vi) interference of HBV by other viruses. The precise prevalence of occult HBV infection remains to be defined. The clinical implications of occult HBV infection involve different clinical aspects. First of all, occult HBV infection harbours potential risk of HBV transmission through blood transfusion, haemodialysis, and organ transplantation. Second, it may serve as the cause of cryptogenic liver disease, contribute to acute exacerbation of chronic hepatitis B, or even fulminant hepatitis. Third, it is associated with development of hepatocellular carcinoma. Fourth, it may affect disease progression and treatment response of chronic hepatitis C. Most of the previous studies utilized retrospective observation without control groups, and lacked direct association of occult HBV infection with specific pathological changes and disease progression. Highly sensitive, quantitative, and functional molecular analyses of HBV, combined with a well-designed prospective clinical assessment will provide the best approach for the future study of occult HBV infection.
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Affiliation(s)
- Ke-Qin Hu
- Transplantation Institute and Division of Gastroenterology, Loma Linda University Medical Center and Jerry L. Pettis Memorial VA Medical Center, Loma Linda, California 92354, USA.
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Chlabicz S, Grzeszczuk A. Prevalence of hepatitis B markers in patients with hepatitis C infection in north-eastern Poland: risk factors and vaccine use. Eur J Epidemiol 2002; 17:267-70. [PMID: 11680546 DOI: 10.1023/a:1017934410028] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
We evaluated the prevalence of hepatitis B virus (HBV) markers and established HBV vaccination status among 111 patients with hepatitis C virus (HCV) infection. A history of HBV immunisation was recorded in 30 patients (27.0%) and only 17/30 (66.7%) had anti-HBs level > or =10 mIU/ml. All patients were HBsAg-negative and 22.2% of nonvaccinated subjects had evidence of HBV infection as determined by anti-HBc presence. Among patients with anti-HBc in 7/18 cases (38.9%) anti-HBc was the only marker of HBV infection (without anti-HBs). The prevalence of anti-HBc was significantly higher among patients who reported a history of acute hepatitis. In conclusion the prevalence of HBV markers in patients with HCV infection in north-eastern Poland is similar to the prevalence in general population, which suggests no increased risk for nosocomial HBV infection among those individuals. HCV infection seems to favour unusual serological pattern of HBV infection with anti-HBc as the only marker. HBV vaccine use is low among patients with HCV infection in north-eastern Poland.
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Affiliation(s)
- S Chlabicz
- Department of Infectious Diseases, University Medical School in Białystok, Poland.
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50
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Yano Y, Yamashita F, Sumie S, Ando E, Fukumori K, Kiyama M, Oyama T, Kuroki S, Kato O, Yamamoto H, Tanaka M, Sata M. Clinical features of hepatocellular carcinoma seronegative for both HBsAg and anti-HCV antibody but positive for anti-HBc antibody in Japan. Am J Gastroenterol 2002; 97:156-61. [PMID: 11808941 DOI: 10.1111/j.1572-0241.2002.05440.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE We determined the prevalence of patients with hepatocellular carcinoma (HCC) who were positive for only anti-hepatitis B core (anti-HBc) antibody among 284 Japanese patients and compared their clinical features to those who were hepatitis B surface antigen positive [HBsAg(+)]. METHODS Serum HBsAg and anti-hepatitis C virus (anti-HCV) antibody were examined for all HCC patients. Testing for anti-HBc antibody was performed in the HBsAg(-)/anti-HCV(-) patients. The clinical factors and the survival rate were compared between the HBsAg(+) patients (HCC-B) and those positive for anti-HBc alone (HCC-PB). RESULTS There were 19 (6.7%) HBsAg(+), 236 (83.1%) anti-HCV(+), seven (2.5%) HBsAg(+)/anti-HCV(+), and 22 (7.7%) HBsAg(-)/anti-HCV(-) among the 284 patients tested. Sixteen (72.7%) of the 22 HBsAg(-)/anti-HCV(-) patients were assigned to the HCC-PB group. The prevalence of positivity for anti-HBc alone among all 284 HCC patients was 5.6%. Significant differences between the HCC-PB and HCC-B groups were that age at diagnosis was higher in the HCC-PB group (72.1 yr) than in the HCC-B group (56.2 yr) (p < 0.001), the serum alpha-fetoprotein concentrations were lower in the HCC-PB group (8.2 ng/ml) than in the HCC-B group (43 ng/ml) (p = 0.0488), and a higher familial history of liver disease was observed in the HCC-B group (p = 0.0373). However, there was no significant difference in the cumulative survival rate. CONCLUSIONS Positivity for anti-HBc alone is not rare compared to HBsAg(+), and the clinical features of positivity for anti-HBc alone are similar to those of HBsAg(+). Some differences in the clinical features between the two groups may be explained by differences in the time of first exposure to hepatitis B virus. Therefore, the natural course of acute hepatitis B may be reconsidered.
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Affiliation(s)
- Yoichi Yano
- Saga Social Insurance Hospital, Hyogo-minami, Saga-shi, Japan
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