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Al-Shuaili HH, Al-Busafi SA, Al-Naamani K, Al-Naamani Z. Predictors of survival among patients with chronic hepatitis C at a tertiary care center in Oman. Saudi J Gastroenterol 2024; 30:45-52. [PMID: 38190454 PMCID: PMC10852148 DOI: 10.4103/sjg.sjg_201_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Revised: 08/09/2023] [Accepted: 08/26/2023] [Indexed: 01/10/2024] Open
Abstract
BACKGROUND Chronic hepatitis C (CHC) is a leading cause of cirrhosis and hepatocellular carcinoma (HCC) worldwide. This study aimed to determine rates and predictors of survival among Omani patients with CHC at a tertiary hospital in Muscat, Oman. METHODS This ambidirectional cohort study included all CHC patients who presented to the Sultan Qaboos University Hospital between January 2009 and December 2017. Baseline demographic, clinical, laboratory, and radiological data were analyzed. Patients were followed-up until death or the endpoint of the study (April 2022) to determine survival and associations with other parameters. RESULTS A total of 702 CHC patients were included, of which 398 (56.7%) were under 50 years of age and 477 (67.9%) were male. Overall, 180 patients (25.6%) died by the study endpoint. The mean duration of follow-up was 93.3 ± 48.0 months. The 5-year survival rate was estimated to be 80.5%, while the 10-year survival was 73%. Sustained virological response and the absence of diabetes mellitus, chronic kidney disease, HCC, or other malignancies were associated with significantly better overall survival. The 3- and 5-year survival rate of patients with hepatitis C virus (HCV)-related HCC was 46.5% and 27.6%, respectively, with a median survival of 29.5 months. Co-infection with hepatitis B was associated with poor survival among this subgroup; conversely, early HCV screening and the presence of a single HCC lesion were associated with better overall survival. CONCLUSIONS National policies for early CHC screening and rapid treatment are needed to improve survival rates in this population.
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Affiliation(s)
| | - Said A. Al-Busafi
- Department of Medicine, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman
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Gömer A, Delarocque J, Puff C, Nocke MK, Reinecke B, Baumgärtner W, Cavalleri JMV, Feige K, Steinmann E, Todt D. Dose-Dependent Hepacivirus Infection Reveals Linkage between Infectious Dose and Immune Response. Microbiol Spectr 2022; 10:e0168622. [PMID: 35993785 PMCID: PMC9602444 DOI: 10.1128/spectrum.01686-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 08/03/2022] [Indexed: 12/31/2022] Open
Abstract
More than 70 million people worldwide are still infected with the hepatitis C virus 30 years after its discovery, underscoring the need for a vaccine. To develop an effective prophylactic vaccine, detailed knowledge of the correlates of protection and an immunocompetent surrogate model are needed. In this study, we describe the minimum dose required for robust equine hepacivirus (EqHV) infection in equids and examined how this relates to duration of infection, seroconversion, and transcriptomic responses. To investigate mechanisms of hepaciviral persistence, immune response, and immune-mediated pathology, we inoculated eight EqHV naive horses with doses ranging from 1-2 copies to 1.3 × 106 RNA copies per inoculation. We characterized infection kinetics, pathology, and transcriptomic responses via next generation sequencing. The minimal infectious dose of EqHV in horses was estimated at 13 RNA copies, whereas 6 to 7 copies were insufficient to cause infection. Peak viremia did not correlate with infectious dose, while seroconversion and duration of infection appeared to be affected. Notably, seroconversion was undetectable in the low-dose infections within the surveillance period (40 to 50 days). In addition, transcriptomic analysis revealed a nearly dose-dependent effect, with greater immune activation and inflammatory response observed in high-dose infections than in low-dose infections. Interestingly, inoculation with 6-7 copies of RNA that did not result in productive infection, but was associated with a strong immune response, similar to that observed in the high-dose infections. IMPORTANCE We demonstrate that the EqHV dose of infection plays an important role for inducing immune responses, possibly linked to early clearance in high-dose and prolonged viremia in low-dose infections. In particular, pathways associated with innate and adaptive immune responses, as well as inflammatory responses, were more strongly upregulated in high-dose infections than in lower doses. Hence, inoculation with low doses may enable EqHV to evade strong immune responses in the early phase and therefore promote robust, long-lasting infection.
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Affiliation(s)
- André Gömer
- Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany
- Institute of Virology, University of Veterinary Medicine Hannover, Hanover, Germany
| | - Julien Delarocque
- Clinic for Horses, University of Veterinary Medicine Hannover, Hanover, Germany
| | - Christina Puff
- Department of Pathology, University of Veterinary Medicine Hannover, Hanover, Germany
| | - Maximilian K. Nocke
- Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany
| | - Birthe Reinecke
- Institute of Experimental Virology, TWINCORE Centre for Experimental and Clinical Infection Research, Hanover, Germany
| | - Wolfgang Baumgärtner
- Department of Pathology, University of Veterinary Medicine Hannover, Hanover, Germany
| | - Jessika M. V. Cavalleri
- Clinical Section of Equine Internal Medicine, Department of Companion Animals and Horses, University of Veterinary Medicine Vienna, Vienna, Austria
| | - Karsten Feige
- Clinic for Horses, University of Veterinary Medicine Hannover, Hanover, Germany
| | - Eike Steinmann
- Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany
| | - Daniel Todt
- Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany
- European Virus Bioinformatics Center (EVBC), Jena, Germany
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Tarao K, Nozaki A, Ikeda T, Sato A, Komatsu H, Komatsu T, Taguri M, Tanaka K. Real impact of liver cirrhosis on the development of hepatocellular carcinoma in various liver diseases-meta-analytic assessment. Cancer Med 2019; 8:1054-1065. [PMID: 30791221 PMCID: PMC6434205 DOI: 10.1002/cam4.1998] [Citation(s) in RCA: 102] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2018] [Revised: 12/27/2018] [Accepted: 01/06/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND It is well known that the incidence of developing hepatocelluler carcinoma (HCC) is increased in liver cirrhosis of different etiologies. However, comparison of HCC incidence in various liver diseases has not yet been estimated. We surveyed this comparison. METHODS The PubMed database was examined (1989-2017) for studies published in English language regarding the prospective follow-up results for the development of HCC in various liver diseases. A meta-analysis was performed for each liver disease. RESULTS The annual incidence (%) of HCC in the non-cirrhotic stage and cirrhotic stage, and the ratio of HCC incidence in the cirrhotic stage/non-cirrhotic stage were as follows. (a) hepatitis B virus liver disease: 0.37%→3.23% (8.73-fold), (b) hepatitis C virus liver diseases: 0.68%→4.81% (7.07-fold), (c) primary biliary cholangitis (0.26%→1.79%, 6.88-fold), (d) autoimmune hepatitis (0.19%→0.53%, 2.79-fold), and (e) NASH (0.03%→1.35%, 45.00-fold). Regarding primary hemochromatosis and alcoholic liver diseases, only follow-up studies in the cirrhotic stage were presented, 1.20% and 2.06%, respectively. CONCLUSIONS When the liver diseases advance to cirrhosis, the incidence of HCC is markedly increased. The development of HCC must be closely monitored by ultrasonography, magnetic resonance imaging, and computed tomography, irrespective of the different kinds of liver diseases.
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Affiliation(s)
- Kazuo Tarao
- Tarao’s Gastroenterological ClinicYokohamaJapan
| | - Akito Nozaki
- Gastroenterological Center, Medical CenterYokohama City UniversityYokohamaJapan
| | - Takaaki Ikeda
- Gastroenterology DepartmentYokosuka General Hospital UwamachiYokosukaJapan
| | - Akira Sato
- Division of Gastroenterology, Department of Internal MedicineSt. Marianna University, Yokohama City Seibu HospitalYokohamaJapan
| | - Hirokazu Komatsu
- Department of GastroenterologyYokohama Municipal Citizen’s HospitalYokohamaJapan
| | - Tatsuji Komatsu
- Department Clinical ResearchNational Hospital Organization, Yokohama Medical CenterYokohamaJapan
| | - Masataka Taguri
- Department of Data ScienceYokohama City UniversityYokohamaJapan
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Mahajan R, Midha V, Goyal O, Mehta V, Narang V, Kaur K, Singh A, Singh D, Bhanot R, Sood A. Clinical profile of hepatitis C virus infection in a developing country: India. J Gastroenterol Hepatol 2018; 33:926-933. [PMID: 28921677 DOI: 10.1111/jgh.13995] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2017] [Revised: 08/20/2017] [Accepted: 09/11/2017] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND AIM The epidemiology and clinical profile of hepatitis C virus (HCV) varies worldwide, and data from developing countries are sparse. The aim of the present study was to assess the clinical profile of HCV infection in a developing country in South-East Asia (India). METHODS This observational study assessed patient demographics, viral characteristics, risk factors for virus acquisition, and disease characteristics in HCV patients diagnosed between January 2004 and December 2015. RESULTS Of 8035 patients who were diagnosed with HCV infection, a majority were men (68.3%), middle aged (52.2%), and from low (34%) to middle (46%) socioeconomic status and rural population (69.8%). Eighty-two percent had identifiable risk factors, the most common being history of dental treatment (52%) and therapeutic injections with reusable syringes/needles (45%). Household contacts of index patients had high prevalence of HCV (15.3%). Common genotypes were genotype 3 (70.4%) and genotype 1 (19.3%). Although a majority of patients were either asymptomatic (54.8%) or had non-specific symptoms (6.7%) at presentation, a significant proportion (9.3%) had advanced liver disease. Presentation with cirrhosis (38.8%) was associated with male gender, higher age at time of virus detection, rural residence, alcohol or opium intake, and coinfections with hepatitis B virus or human immunodeficiency virus. CONCLUSIONS Hepatitis C virus infection in northern India is seen more commonly in men, the middle aged and people from rural background and low to middle socioeconomic status. The common possible risk factors are dental treatment and exposure to reused syringes and needles. Although the most common presentation is incidental detection, a large number of patients present with advanced liver disease.
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Affiliation(s)
- Ramit Mahajan
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | - Vandana Midha
- Department of Internal Medicine, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | - Omesh Goyal
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | - Varun Mehta
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | - Vikram Narang
- Department of Pathology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | - Kirandeep Kaur
- Department of Pharmacology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | - Arshdeep Singh
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | - Dharmatma Singh
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | - Rishu Bhanot
- Department of Internal Medicine, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | - Ajit Sood
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
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Abstract
It is critical to recognize that hepatitis C virus (HCV) infection is, in fact, a multifaceted systemic disease with both hepatic and extrahepatic complications. It is also important to recognize that the comprehensive burden of HCV should include not only its clinical burden but also its burden on the economic and patient-reported outcomes. It is only through this comprehensive approach to HCV infection that we can fully appreciate its true burden and understand the full benefit of curing HCV for the patient and the society.
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Affiliation(s)
- Zobair M Younossi
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, 3300 Gallows Road, Falls Church, VA 22042, USA; Department of Medicine, Center for Liver Disease, Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA 22042, USA.
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Ahmed KT, Almashhrawi AA, Ibdah JA, Tahan V. Is the 25-year hepatitis C marathon coming to an end to declare victory? World J Hepatol 2017; 9:921-929. [PMID: 28824743 PMCID: PMC5545137 DOI: 10.4254/wjh.v9.i21.921] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2017] [Revised: 06/04/2017] [Accepted: 07/10/2017] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) which was originally recognized as posttransfusion non-A, non-B hepatitis has been a major global health problem affecting 3% of the world population. Interferon/peginterferon and ribavirin combination therapy was the backbone of chronic HCV therapy for two decades of the journey. However, the interferon based treatment success rate was around 50% with many side effects. Many chronic HCV patients with psychiatric diseases, or even cytopenias, were ineligible for HCV treatment. Now, we no longer need any injectable medicine. New direct-acting antiviral agents against HCV allowed the advance of interferon-free and ribavirin-free oral regimens with high rates of response and tolerability. The cost of the medications should not be a barrier to their access in certain parts of the world. While we are getting closer, we should still focus on preventing the spread of the disease, screening and delivering the cure globally to those in need. In the near future, development of an effective vaccine against HCV would make it possible to eradicate HCV infection worldwide completely.
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Younossi ZM, Birerdinc A, Henry L. Hepatitis C infection: A multi-faceted systemic disease with clinical, patient reported and economic consequences. J Hepatol 2016; 65:S109-S119. [PMID: 27641981 DOI: 10.1016/j.jhep.2016.07.005] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2016] [Revised: 07/02/2016] [Accepted: 07/04/2016] [Indexed: 12/21/2022]
Abstract
Hepatitis C virus infection (HCV) affects approximately 170-200 million individuals globally. HCV is one of the primary causes of hepatocellular carcinoma (HCC) and cirrhosis and has been identified as the leading indication for liver transplantation in most Western countries. Because HCV is a systemic disease with hepatic, extrahepatic, economic and patient reported consequences, it is important for healthcare practitioners to understand the comprehensive and multi-faceted picture of this disease. In this context, it is important to fully appreciate the impact of HCV on the individual patient and the society. With the recent advent of the new generation of direct antiviral agents, the long standing goal of eradicating HCV in most infected patients has been accomplished. Therefore, now more than ever, it is critical to assess the total benefits of sustained virological response in a comprehensive manner. This should not be limited to the clinical benefits of HCV cure, but also to account for the improvement of patient reported health and economic outcomes of HCV cure. It is only through this comprehensive approach to HCV and its treatment that we will understand the full impact of this disease and the tremendous gains that have been achieved with the new antiviral regimens.
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Affiliation(s)
- Zobair M Younossi
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, USA.
| | - Aybike Birerdinc
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, USA
| | - Linda Henry
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, USA
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Abstract
Hepatocellular carcinoma (HCC) is the seventh most common malignancy worldwide. HCC meets all the criteria established by the World Health Organization for performing surveillance on those at-risk for developing cancer. Although there are consensus guidelines in the United States, Europe, and Asia for HCC surveillance, it is unclear if these guidelines are regularly implemented in routine practice to optimize real-life clinical outcomes. We reviewed the current literature on the adherence to current HCC practice guidelines by the American Association for the Study of Liver Diseases (2009), the European Association for the Study of the Liver (2012), and the Asia Pacific Association for the Study of the Liver (2010) for screening/surveillance and outcomes of optimal versus poor adherence. We performed PubMed search for relevant articles regarding HCC surveillance and screening worldwide. Currently, HCC screening is underutilized to a large extent. In most studies, the adherence to HCC screening and surveillance is suboptimal. Various patient, provider, and health care system factors may have all contributed to such nonadherence. Strategies to improve HCC screening and surveillance are urgently needed for early HCC detection and improved survival of HCC patients. Further research is needed to elucidate the various medical and/or cultural knowledge, belief, and practice patterns that can lead to barriers to HCC screening and surveillance at both patient and provider levels. These data will help focus and target advocacy and educational efforts to improve HCC surveillance at all levels: patients, providers, and health care system/government.
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9
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Perumpail RB, Hahambis TA, Aggarwal A, Younossi ZM, Ahmed A. Treatment strategies for chronic hepatitis C prior to and following liver transplantation. World J Hepatol 2016; 8:69-73. [PMID: 26783422 PMCID: PMC4705454 DOI: 10.4254/wjh.v8.i1.69] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2015] [Revised: 10/30/2015] [Accepted: 12/18/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV)-related liver disease is the leading indication for liver transplantation (LT) worldwide. However, HCV is an independent predictor of lower survival following LT, and recurrence of HCV post-LT is virtually universal. The historic standard of care during the interferon era of HCV therapy was expectant management-initiation of antiviral therapy in the setting of documented disease progression following LT. With the advent of new direct acting antiviral (DAA) therapies for HCV, the paradigm of expectant treatment for recurrent HCV infection post-LT is shifting. The safety, tolerability, and efficacy of DAAs, even among the sickest patients with advanced liver disease, enables treatment of HCV in the pre-transplant setting among LT waitlist registrants. Finally, emerging data are supportive of preemptive therapy with DAAs in liver transplant recipients as the preferred approach. Expectant management of HCV following LT can rarely be justified in the modern era of HCV therapy.
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Sheiko MA, Rosen HR. Hepatic Fibrosis in Hepatitis C. HEPATITIS C VIRUS II 2016:79-108. [DOI: 10.1007/978-4-431-56101-9_3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Smith DJ, Combellick J, Jordan AE, Hagan H. Hepatitis C virus (HCV) disease progression in people who inject drugs (PWID): A systematic review and meta-analysis. THE INTERNATIONAL JOURNAL OF DRUG POLICY 2015; 26:911-21. [PMID: 26298331 PMCID: PMC4577462 DOI: 10.1016/j.drugpo.2015.07.004] [Citation(s) in RCA: 78] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2015] [Revised: 05/27/2015] [Accepted: 07/07/2015] [Indexed: 12/12/2022]
Abstract
BACKGROUND Understanding HCV disease progression rates among people who inject drugs (PWID) is important to setting policy to expand access to detection, diagnosis and treatment, and in forecasting the burden of disease. In this paper we synthesize existing data on the natural history of HCV among PWID, including fibrosis progression rates (FPR) and the incidence of compensated cirrhosis (CC), decompensated cirrhosis (DC), and hepatocellular carcinoma (HCC). METHODS We conducted electronic and manual searches for published and unpublished literature. Reports were eligible if they (i) included participants who were chronically infected with HCV and reported current or previous injection drug use; (ii) presented original data on disease progression in a study sample comprised of at least 90% PWID; (iii) published between January 1, 1990, and December 31, 2013; and (iv) included data from upper-middle- or high-income countries. Quality ratings were assigned using an adaptation of the Quality In Prognosis Studies (QUIPS) tool. We estimated pooled FPRs using the stage-constant and stage-specific methods, and pooled incidence rates of CC, DC, and HCC. RESULTS Twenty-one reports met the study inclusion criteria. Based on random-effect models, the pooled stage-constant FPR was 0.117 METAVIR units per year (95% CI, 0.099-0.135), and the stage-specific FPRs were F0→F1, 0.128 (95% CI 0.080, 0.176); F1→F2, 0.059 (95% CI 0.035, 0.082); F2→F3, 0.078 (95% CI 0.056, 0.100); and F3→F4, 0.116 (95% CI 0.070, 0.161). The pooled incidence rates of CC, DC, and HCC were 6.6 (95% CI 4.8, 8.4), 1.1 (95% CI 0.8, 1.4), and 0.3 (95% CI -0.1, 0.6) events per 1000 person-years, respectively. Following the stage-constant estimate, average time to cirrhosis is 34 years post-infection, and time to METAVIR stage F3 is 26 years; using the stage-specific estimates, time to cirrhosis is 46 years and time to F3 is 38 years. CONCLUSION Left untreated, PWID with chronic HCV infection will develop liver sequelae (including HCC) in mid- to late-adulthood. Delaying treatment with the new drug regimens until advanced fibrosis develops prolongs the period of infectiousness to perhaps thirty years. Scaling up of effective HCV prevention and early engagement in care and treatment will facilitate the elimination HCV as a source of serious disease in PWID.
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Affiliation(s)
| | | | - Ashly E Jordan
- College of Nursing, New York University, NY, NY, USA; Center for Drug Use and HIV Research, New York University, NY, NY, USA
| | - Holly Hagan
- College of Nursing, New York University, NY, NY, USA; Center for Drug Use and HIV Research, New York University, NY, NY, USA
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Gordon SC, Lamerato LE, Rupp LB, Holmberg SD, Moorman AC, Spradling PR, Teshale E, Xu F, Boscarino JA, Vijayadeva V, Schmidt MA, Oja-Tebbe N, Lu M. Prevalence of cirrhosis in hepatitis C patients in the Chronic Hepatitis Cohort Study (CHeCS): a retrospective and prospective observational study. Am J Gastroenterol 2015; 110. [PMID: 26215529 PMCID: PMC5731242 DOI: 10.1038/ajg.2015.203] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES The severity of liver disease in the hepatitis C virus (HCV)-infected population in the United States remains uncertain. We estimated the prevalence of cirrhosis in adults with chronic hepatitis C (CHC) using multiple parameters including liver biopsy, diagnosis/procedure codes, and a biomarker. METHODS Patients enrolled in the Chronic Hepatitis Cohort Study (CHeCS) who received health services during 2006-2010 were included. Cirrhosis was identified through liver biopsy reports, diagnosis/procedure codes for cirrhosis or hepatic decompensation, and Fibrosis-4 (FIB-4) scores ≥5.88. Demographic and clinical characteristics associated with cirrhosis were identified through multivariable logistic modeling. RESULTS Among 9,783 patients, 2,788 (28.5%) were cirrhotic by at least one method. Biopsy identified cirrhosis in only 661 (7%) patients, whereas FIB-4 scores and diagnosis/procedure codes for cirrhosis and hepatic decompensation identified cirrhosis in 2,194 (22%), 557 (6%), and 482 (5%) patients, respectively. Among 661 patients with biopsy-confirmed cirrhosis, only 356 (54%) had an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for cirrhosis. Older age, male gender, Asian race, Hispanic ethnicity, genotype 3 infection, HIV coinfection, diabetes, history of antiviral therapy, and history of alcohol abuse were independently associated with higher odds of cirrhosis (all, P<0.05). Conversely, private health insurance coverage, black race, and HCV genotype 2 were associated with lower odds of cirrhosis. CONCLUSIONS A high proportion of patients with biopsy-confirmed cirrhosis are not assigned ICD-9 codes for cirrhosis. Consequently, ICD-9 codes may not be reliable as the sole indicator of the prevalence of cirrhosis in cohort studies. Use of additional parameters suggests a fourfold higher prevalence of cirrhosis than is revealed by biopsy alone. These findings suggest that cirrhosis in CHC patients may be significantly underdocumented and underdiagnosed.
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Affiliation(s)
- Stuart C. Gordon
- Division of Gastroenterology and Hepatology, Henry Ford Health System, Detroit, Michigan, USA
| | - Lois E. Lamerato
- Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan, USA
| | - Loralee B. Rupp
- Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, Michigan, USA
| | - Scott D. Holmberg
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Anne C. Moorman
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Philip R. Spradling
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Eyasu Teshale
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Fujie Xu
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Joseph A. Boscarino
- Center for Health Research, Geisinger Health System, Danville, Pennsylvania, USA
| | - Vinutha Vijayadeva
- Center for Health Research, Kaiser Permanente-Hawaii, Honolulu, Hawaii, USA
| | - Mark A. Schmidt
- Center For Health Research, Kaiser Permanente-Northwest, Portland, Oregon, USA
| | - Nancy Oja-Tebbe
- Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan, USA
| | - Mei Lu
- Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan, USA
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Tokunaga M, Uto H, Oda K, Tokunaga M, Mawatari S, Kumagai K, Haraguchi K, Oketani M, Ido A, Ohnou N, Utsunomiya A, Tsubouchi H. Influence of human T-lymphotropic virus type 1 coinfection on the development of hepatocellular carcinoma in patients with hepatitis C virus infection. J Gastroenterol 2014; 49:1567-77. [PMID: 24463696 DOI: 10.1007/s00535-013-0928-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2013] [Accepted: 12/13/2013] [Indexed: 02/04/2023]
Abstract
BACKGROUND Human T-lymphotropic virus type 1 (HTLV-1) may worsen the clinical course of hepatitis C virus (HCV) infection. The aim of this study was to investigate whether HTLV-1 coinfection influences the clinical characteristics of patients with HCV infection. METHODS This retrospective study included 523 consecutive patients from January 2001 to December 2010 with chronic liver disease due to HCV infection, in whom serum anti-HTLV-1 antibodies were examined. Among these patients, 265 were diagnosed with hepatocellular carcinoma (HCC). RESULTS The seroprevalence of anti-HTLV-1 antibodies was significantly higher in patients with HCC (21.1%) than those without HCC (10.5%, P = 0.001). This significant difference was observed in female patients (29.5 vs. 8.5%, P < 0.001), but not in male patients (16.5 vs. 12.9%, P = 0.501). In multivariate analysis, anti-HTLV-1 antibody positivity was independently associated with HCC in female patients [odds ratio (OR), 5.029; 95% confidence interval (95% CI), 1.760-14.369; P = 0.003], in addition to age (≥65 years; OR, 10.297; 95% CI, 4.322-24.533; P < 0.001), platelet count (<15 × 10(4)/μL; OR, 2.715; 95% CI, 1.050-7.017; P = 0.039), total bilirubin (≥1 mg/dL; OR, 3.155; 95% CI, 1.365-7.292; P = 0.007), and total cholesterol (≤160 mg/dL; OR, 2.916; 95% CI, 1.341-6.342; P = 0.007). In contrast, HTLV-1 coinfection was not associated with HCC in male patients, although age, alcohol consumption, platelet count, and albumin were independently associated with HCC. CONCLUSIONS HTLV-1 coinfection may contribute to the development of HCC in patients with chronic HCV infection, especially in females.
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Affiliation(s)
- Mayumi Tokunaga
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
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Li JF, Liu S, Ren F, Liu M, Wu HL, Chen Y, Zou HB, Bai L, Li Y, Zheng SJ, Duan ZP. Fibrosis progression in interferon treatment-naive Chinese plasma donors with chronic hepatitis C for 20 years: a cohort study. Int J Infect Dis 2014; 27:49-53. [PMID: 25168642 DOI: 10.1016/j.ijid.2014.07.003] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2014] [Revised: 07/03/2014] [Accepted: 07/03/2014] [Indexed: 12/22/2022] Open
Abstract
OBJECTIVES To evaluate the progression of fibrosis and factors influencing this in interferon (IFN) treatment-naive Chinese plasma donors infected with hepatitis C virus (HCV) for approximately 20 years. METHODS From July 2010 to June 2011, we investigated 122 IFN treatment-naive chronic hepatitis C (CHC) patients infected by plasma donation in 1992-1995. Liver fibrosis stage and inflammation grade were evaluated by Metavir and Scheuer scoring systems, respectively. RESULTS One hundred and twenty patients underwent liver biopsy. Liver biopsy was not performed in one patient with cirrhosis due to ascites, and another patient was excluded because of an invalid biopsy specimen. Cirrhosis was observed in three patients (fibrosis stage F4 in two patients revealed by biopsy, and one patient with ascites confirmed by physical and Doppler ultrasound examination). Fibrosis stages F1 and F2 were present in 55 and 50 patients, respectively. The severity of liver inflammation was independently related to moderate to severe fibrosis (F ≥2). Older age and male sex showed an increasing tendency for more severe fibrosis (F3/F4) in the present cohort. CONCLUSIONS Based on histopathology results, the progression of fibrosis in patients with CHC infected by repeated plasma donation is slow after HCV infection of approximately 20 years. Liver inflammation is closely related to the development of moderate to severe liver fibrosis.
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Affiliation(s)
- Jun-Feng Li
- Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, 8 Xitoutiao, Youwai Street, Beijing 100069, China; The First Clinical Medical School, Lanzhou University, 1 Donggangxi Road, Lanzhou 730000, China
| | - Shuang Liu
- Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, 8 Xitoutiao, Youwai Street, Beijing 100069, China
| | - Feng Ren
- Institute of Liver Diseases, Beijing YouAn Hospital, Capital Medical University, 8 Xitoutiao, Youwai Street, Beijing 100069, China
| | - Mei Liu
- Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, 8 Xitoutiao, Youwai Street, Beijing 100069, China
| | - Hui-Li Wu
- Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, 8 Xitoutiao, Youwai Street, Beijing 100069, China
| | - Yu Chen
- Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, 8 Xitoutiao, Youwai Street, Beijing 100069, China
| | - Huai-Bin Zou
- Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, 8 Xitoutiao, Youwai Street, Beijing 100069, China
| | - Li Bai
- Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, 8 Xitoutiao, Youwai Street, Beijing 100069, China
| | - Ying Li
- Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, 8 Xitoutiao, Youwai Street, Beijing 100069, China
| | - Su-Jun Zheng
- Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, 8 Xitoutiao, Youwai Street, Beijing 100069, China.
| | - Zhong-Ping Duan
- Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, 8 Xitoutiao, Youwai Street, Beijing 100069, China.
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Yan MX, Yang J, Sun Q, Liu CH, Wang YG, Wang WQ. Hepatocellular carcinoma that arose from primary Sjögren’s syndrome. Ann Hepatol 2013; 12:824-829. [DOI: 10.1016/s1665-2681(19)31327-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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Regulation of hepatitis C virus replication by nuclear translocation of nonstructural 5A protein and transcriptional activation of host genes. J Virol 2013; 87:5523-39. [PMID: 23468497 DOI: 10.1128/jvi.00585-12] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is involved in regulating viral replication through its direct interaction with the HCV RNA-dependent RNA polymerase. NS5A also alters infected cell metabolism through complex interactions with numerous host cell proteins. NS5A has furthermore been suggested to act as a transcriptional activator, although the impact on viral replication is unclear. To study this, HCV NS5A variants were amplified from hepatic tissue from an HCV-infected patient, and their abilities to activate gene transcription were analyzed in a single-hybrid yeast (Saccharomyces cerevisiae) model. Different variants isolated from the same patient displayed different transactivational activities. When these variants were inserted into the HCV subgenomic replicon system, they demonstrated various levels of RNA replication, which correlated with their transactivational activities. We showed that the C-terminal fragment of NS5A was localized to the nucleus and that a functional NS5A nuclear localization signal and cellular caspase activity were required for this process. Furthermore, nuclear localization of NS5A was necessary for viral replication. Finally, we demonstrate that nuclear NS5A binds to host cell promoters of several genes previously identified as important for efficient HCV RNA replication, inducing their transcription. Taken together, these results demonstrate a new mechanism by which HCV modulates its cellular environment, thereby enhancing viral replication.
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17
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Ghosh S, Kaplan KJ, Schrum LW, Bonkovsky HL. Cytoskeletal proteins: shaping progression of hepatitis C virus-induced liver disease. INTERNATIONAL REVIEW OF CELL AND MOLECULAR BIOLOGY 2013; 302:279-319. [PMID: 23351713 DOI: 10.1016/b978-0-12-407699-0.00005-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Hepatitis C virus (HCV) infection, which results in chronic hepatitis C (CHC) in most patients (70-85%), is a major cause of liver disease and remains a major therapeutic challenge. The mechanisms determining liver damage and the key factors that lead to a high rate of CHC remain imperfectly understood. The precise role of cytoskeletal (CS) proteins in HCV infection remains to be determined. Some studies including our recent study have demonstrated that changes occur in the expression of CS proteins in HCV-infected hepatocytes. A variety of host proteins interact with HCV proteins. Association between CS and HCV proteins may have implications in future design of CS protein-targeted therapy for the treatment for HCV infection. This chapter will focus on the interaction between host CS and viral proteins to signify the importance of this event in HCV entry, replication and transportation.
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Affiliation(s)
- Sriparna Ghosh
- Liver-Biliary-Pancreatic Center, Carolinas Medical Center, and School of Medicine, University of North Carolina, Carolinas Medical Center, Charlotte, NC, USA.
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18
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Incidence of hepatocellular carcinoma among US patients with cirrhosis of viral or nonviral etiologies. Clin Gastroenterol Hepatol 2012; 10:1412-7. [PMID: 22902757 PMCID: PMC3511850 DOI: 10.1016/j.cgh.2012.08.011] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2012] [Revised: 08/01/2012] [Accepted: 08/06/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS We aimed to identify risk factors for hepatocellular carcinoma (HCC) in patients with cirrhosis in the United States. We performed a prospective study to identify associations between etiologies of cirrhosis and ethnicity with HCC incidence. METHODS We used convenience sampling to select a cohort of 379 patients with cirrhosis who visited the liver clinic at the Stanford University Medical Center from 2001 to 2009 (65% male, 75% white or Hispanic, and 20% Asian). Study end points were HCC diagnosis by histology or noninvasive criteria, liver transplantation, or last screening without HCC. Patients were followed up, with ultrasound or computed tomographic imaging analyses and measurements of serum levels of α-fetoprotein, approximately every 6 months, for a median time of 34 months (range, 6-99 mo). RESULTS The etiologies of cirrhosis in the cohort were 68% hepatitis C, 7% hepatitis B, and 25% nonviral. Forty-four patients (12%) were diagnosed with HCC during the follow-up period. Patients with cirrhosis related to viral hepatitis had a statistically significantly higher incidence of HCC than those with nonviral diseases in Kaplan-Meier analysis (P = .04). There was no statistically significant difference in HCC incidence between Asian and non-Asian patients. In a multivariate Cox proportional hazards model that included age, sex, ethnicity, etiology, and Child-Pugh-Turcotte score, viral cirrhosis was associated significantly with HCC, compared with nonviral cirrhosis (hazard ratio, 3.6; 95% confidence interval, 1.3-10.1; P = .02) but Asian ethnicity was not. CONCLUSIONS In a diverse cohort of patients in the United States with cirrhosis, a viral etiology of cirrhosis was associated with increased incidence of HCC, but Asian ethnicity was not. These findings indicate the importance of cirrhosis etiology in determining risk for HCC.
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19
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Ydreborg M, Söderström A, Håkanson A, Alsiö Å, Arnholm B, Malmström P, Hellstrand K, Westin J, Lagging M. Look-back screening for the identification of transfusion-induced hepatitis C virus infection in Sweden. ACTA ACUST UNITED AC 2011; 43:522-7. [DOI: 10.3109/00365548.2011.562526] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Teufel A, Weinmann A, Centner C, Piendl A, Lohse AW, Galle PR, Kanzler S. Hepatocellular carcinoma in patients with autoimmune hepatitis. World J Gastroenterol 2009; 15:578-82. [PMID: 19195059 PMCID: PMC2653348 DOI: 10.3748/wjg.15.578] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate and confirm the low incidence of hepatocellular carcinoma (HCC) in patients with autoimmune hepatitis (AIH). At present only very few cases of HCC in patients with AIH and definite exclusion of chronic viral hepatitis have been published, suggesting that HCC due to AIH is rare.
METHODS: In order to further investigate the incidence of HCC in patients with AIH, we reviewed our large cohort of 278 patients with AIH.
RESULTS: Eighty-nine patients (32%) were diagnosed with liver cirrhosis, a preneoplastic condition for HCC. We studied a total of 431 patient years of cirrhosis in these patients, an average 4.8 years per patient. During this period none of the patients of our own study cohort developed HCC. However, three patients with HCC due to AIH associated liver cirrhosis were referred to our department for further treatment of HCC. In all three patients chronic viral hepatitis was excluded.
CONCLUSION: We conclude that HCC may under rare circumstances develop due to chronic AIH dependent liver cirrhosis. Compared to other causes of liver cirrhosis such as chronic viral hepatitis, alcohol, or hemochromatosis, the incidence of HCC is significantly lower. Pathophysiological differences between AIH and chronic viral hepatitis responsible for differences in the incidence of HCC are yet to be further characterized and may lead to new therapeutic concepts in prevention and treatment of liver cancer.
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21
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PATEL H, HEATHCOTE EJ. When to treat and the benefits of treating hepatitis C in patients with haemophilia. Haemophilia 2009; 15:20-32. [DOI: 10.1111/j.1365-2516.2008.01917.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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22
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Missiha SB, Ostrowski M, Heathcote EJ. Disease progression in chronic hepatitis C: modifiable and nonmodifiable factors. Gastroenterology 2008; 134:1699-714. [PMID: 18471548 DOI: 10.1053/j.gastro.2008.02.069] [Citation(s) in RCA: 159] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2007] [Revised: 02/15/2008] [Accepted: 02/21/2008] [Indexed: 12/13/2022]
Abstract
The hepatic complications of chronic hepatitis C (CHC) usually occur only after progression to cirrhosis has taken place. Progression to cirrhosis, however, is extremely variable and depends on a broad set of host and viral factors that modify the rate at which fibrosis develops in a given individual. Despite their inherent limitations, studies of the natural history of CHC have identified several nonmodifiable factors associated with disease progression. These include age at acquisition of infection, sex, and race. More recent reports suggest important roles for host genetic polymorphisms and viral factors. Of greater immediate relevance to patients and their clinicians are the potentially modifiable factors, which include excessive alcohol consumption; smoking (tobacco and marijuana); insulin resistance; and coinfection with hepatitis B virus, human immunodeficiency virus type 1, or schistosomiasis. Unfortunately, to date, there are no reliable predictive models that can accurately estimate the risk of CHC disease progression.
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Affiliation(s)
- Sharif B Missiha
- Division of Gastroenterology, University Health Network, University of Toronto, Toronto, Ontario, Canada
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23
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Nouso K, Tanaka H, Uematsu S, Shiraga K, Okamoto R, Onishi H, Nakamura SI, Kobayashi Y, Araki Y, Aoki N, Shiratori Y. Cost-effectiveness of the surveillance program of hepatocellular carcinoma depends on the medical circumstances. J Gastroenterol Hepatol 2008; 23:437-44. [PMID: 17683496 DOI: 10.1111/j.1440-1746.2007.05054.x] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIM The clinical features of hepatocellular carcinoma (HCC) and the medical environment are diverse in different geographic areas. The aim of this study is to evaluate the cost-effectiveness of the surveillance of HCC in different medical circumstances. METHODS The Markov model focused on variables that differ from country to country and may change in the future, especially in regards to the proportion of small HCC detected incidentally. The target population was 45-year-old patients with Child-Pugh class A cirrhosis, and the intervention was surveillance with ultrasonography every 6 months. RESULTS The additional cost of the surveillance was $US15 100, the gain in quality-adjusted life years (QALYs) was 0.50 years, and the incremental cost-effectiveness ratio (ICER) was $US29 900/QALY in a base-case analysis (annual incidence of HCC = 4%). If 40% of small HCC were detected incidentally without surveillance, the gain in QALY decreased to 0.15 and the ICER increased to $US47 900/QALY. The increase in the annual incidence of HCC to 8% resulted in the increase of QALYs to 0.81, and the decrease of the ICER to $US25 400/QALY. The adoption of liver transplantation increased the gain in QALYs and the ICER to 0.84 and $US59 900/QALY, respectively. CONCLUSIONS The gain in QALYs and the ICER due to the surveillance of HCC varies between different patient subgroups and it critically depends on the rate of small HCC detected incidentally without surveillance, as well as the annual incidence of HCC and the adoption of liver transplantation.
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Affiliation(s)
- Kazuhiro Nouso
- Department of Internal Medicine, Hiroshima City Hospital, Hiroshima, Japan.
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Abstract
To describe the spontaneous clearance rate of childhood hepatitis C virus (HCV) infection, to determine whether route of transmission affects the clearance rate and to identify other predictors of clearance. Children with chronic hepatitis C were identified between 1990 and 2001. The rate of spontaneous clearance (defined as >or=2 positive anti-HCV antibody test but negative HCV RNA) was calculated using survival analysis. Univariate and multivariate predictor variables [route of transmission, age at infection, age at last follow-up, alanine aminotransferase (ALT) and gender] for clearance were evaluated. Of 157 patients, 28% of children cleared infection (34 transfusional and 10 nontransfusional cases). The 123 transfusional cases were older at time of infection and at follow-up, compared with the 34 nontransfusional cases. Younger age at follow-up (p < 0.0001) and normal ALT levels (p < 0.0001) favoured clearance. Among cases of neonatal infection, 25% demonstrated spontaneous clearance by 7.3 years. The rate of spontaneous clearance of childhood HCV infection was comparable between transfusional and nontransfusional cases. If clearance occurs, it tends to occur early in infection, at a younger age.
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Affiliation(s)
- L T F Yeung
- Rouge Valley Health System, Centenary Health Centre, Galaxy 12 Child & Teen Clinic, Scarborough, ON, Canada.
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25
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Lurie Y, Landau DA, Blendis L, Baruch Y, Veitsman E, Ackermann Z, Zelber-Sagie S, Halpern Z, Oren R. Acute hepatitis C in Israel: a predominantly iatrogenic disease? J Gastroenterol Hepatol 2007; 22:158-64. [PMID: 17295865 DOI: 10.1111/j.1440-1746.2006.04491.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS Acute hepatitis C virus infection in the era of universal screening of blood products has not disappeared, and is thought to be transmitted primarily via injecting drug use. A growing body of evidence supports iatrogenic transmission as an important mode of transmission. The aim of this study was to examine transmission routes and clinical characteristics in a group of patients with acute hepatitis C in Israel. METHODS A retrospective chart review was conducted in three different liver clinics in Israel, of all new hepatitis C patients. Patients identified as possible acute hepatitis C were re-interviewed and all other sources such as blood bank records and pre-employment check-ups reviewed in order to establish the diagnosis of acute hepatitis C infection and to identify the transmission route. RESULTS Twenty-nine patients were found to have acute hepatitis C, representing 0.75% of all new referrals for hepatitis C. The most frequent (65%) mode of transmission was iatrogenic involving several, often minimal, procedures and clinical settings. The group in which iatrogenic transmission was suspected was older and the patients more often in monogamous relationship compared with other transmission routes groups. Injecting drug use was the second most common route of infection. Spontaneous seroconversion has occurred in approximately one third of the patients. CONCLUSIONS Acute hepatitis C in the post universal blood products screening era was found to be predominantly an iatrogenic disease in the investigated localities. This finding should direct attention and resources towards the development and implementation of preventive measures.
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Affiliation(s)
- Yoav Lurie
- Liver Disease Unit, Gastroenterology Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
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26
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Lodato F, Mazzella G, Festi D, Azzaroli F, Colecchia A, Roda E. Hepatocellular carcinoma prevention: A worldwide emergence between the opulence of developed countries and the economic constraints of developing nations. World J Gastroenterol 2006; 12:7239-49. [PMID: 17143937 PMCID: PMC4087479 DOI: 10.3748/wjg.v12.i45.7239] [Citation(s) in RCA: 61] [Impact Index Per Article: 3.2] [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
Hepatocellular carcinoma (HCC) is the fifth most common neoplasm, the major cause of death in patients with liver cirrhosis, and the third most common cause of cancer-related death in the world. The geographic distribution of HCC varies significantly and 80% of cases occur in developing countries (Far East and South Asia) where the prevalence of viral hepatitis is higher. The treatment of HCC is difficult because most patients are diagnosed when the tumour is in an advanced stage and is not amenable to potential curative therapy, thus prevention is the key to reducing HCC and its related morbidity and mortality. HCC is unique among cancers, occurring mostly in patients with a known risk factor. Ninety percent of HCCs develop in the context of chronic liver diseases and mainly in patients with cirrhosis. Viral hepatitis is the most common cause of HCC worldwide, followed by alcoholic liver disease (ALD) and other causes such as non-alcoholic fatty liver disease (NAFLD), genetic haemocromatosis (GH) and primary biliary cirrhosis in an advanced stage (III-V). In certain areas of the People’s Republic of China, exposure to aflatoxin and HBV infection are thought to be responsible for the extraordinary high risk of HCC. Substantial progresses in the prevention of virusl-related hepatitis (screening of blood units, use of disposable sanitary tools, HBV vaccination) have been achieved in developed countries, but in the same areas, alcohol- and dysmetabolism-related HCCs are emerging problems which require specific interventions in terms of public health measures. In developing countries, economic constraints limit the development of any program for the prevention of viral hepatitis transmission (including health education campaigns, healthcare politics, primary prevention and the improvement of hygienic and sanitary conditions). When viral liver disease is established, only a minority of patients are treated worldwide and benefit a possible preventive effect of medical treatment on HCC development. Thus the real contribution of medical treatment to HCC prevention in patients with chronic viral hepatitis is small. Great efforts are needed to identify more effective medical measures for primary and secondary prevention of HCC.
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Affiliation(s)
- Francesca Lodato
- Dipartimento di Medicina Interna e Gastroenterologia, UO di Gastroenterologia, Via Massarenti 9, Bologna 40138, Italy.
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Cheng JT, Hsien C, Sun HEJ, Tong MJ. The emerging importance of chronic hepatitis C infection in Asian Americans. Am J Gastroenterol 2006; 101:2737-43. [PMID: 17227521 DOI: 10.1111/j.1572-0241.2006.00831.x] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVES To study the demographics, epidemiology, and natural history of chronic hepatitis C in Asian Americans. METHODS This retrospective survey describes 260 Asian Americans with chronic hepatitis C referred to one tertiary center. RESULTS Ninety-two percent of patients were born in Asia. Fifty-one percent reported a history of unsafe therapeutic injections, which was a risk factor only in those with exposure outside the United States (p < 0.0001). A history of transfusion was reported in 41% of patients and was more frequent in those with exposure within the Unites States (p < 0.0001). Only 3.8% reported a history of intravenous drug abuse, which was more frequent in those with exposure within the United States (p < 0.0001). Hepatitis C genotype 1 was detected in 64.2% of patients, genotype 2 in 18.3%, and genotype 6 in 11.3%. Genotype 1 had a significantly lower sustained virologic response rate (32.8%) to interferon treatment, compared with genotype 2 (77.8%) or 6 (69.2%). During a mean follow-up of 6 yr, 26 patients developed hepatocellular carcinoma (HCC). Logistic regression model revealed fibrosis stage 4 (odds ratio [OR] 8.87, 95% confidence interval [CI] 2.97-26.48, p < 0.0001), age at presentation (55 vs 35 yr--OR 3.45, 95% CI 1.22-9.75, p= 0.0194), and baseline albumin level (3.0 vs 4.0 mg/dL--OR 3.47, 95% CI 1.02-11.76, p= 0.0464) were independent predictive factors for HCC development. CONCLUSIONS Asian Americans with a history of unsafe therapeutic injections must be screened for chronic hepatitis C. Antiviral treatment should be initiated prior to development of cirrhosis. Surveillance for HCC must be routinely performed in cirrhosis patients.
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Affiliation(s)
- Jason Tzuying Cheng
- The Liver Center, Huntington Medical Research Institutes, Pasadena, California 91105, USA
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Elefsiniotis IS, Pantazis KD, Ketikoglou ID, Koutsounas SI, Tsianos EV. Changing serological status and low vaccination-induced protection rates against hepatitis B characterize chronic hepatitis C virus-infected injecting drug users in Greece: need for immunization policy. Eur J Gastroenterol Hepatol 2006; 18:1227-31. [PMID: 17033445 DOI: 10.1097/01.meg.0000236888.51838.36] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVE To evaluate the serological status of hepatitis B virus infection among Greek injecting drug users with chronic hepatitis C virus infection; to correlate hepatitis B virus infection status with the possible time of infection and the principal genotype of hepatitis C virus infection. METHODS Two hundred and thirty consecutive injecting drug users with chronic hepatitis C virus infection were evaluated for serological markers of hepatitis B virus infection. One hundred and three of them (44.8%) reported intravenous drug use beginning before 1992 (group A) and 127/230 (55.2%) after 1992 (group B). Statistical analysis of data was based on Student's t-test and chi analyses. RESULTS Eighty-five of 103 patients from group A (82.5%) and 28/127 (22%) from group B had serological markers of previous hepatitis B virus infection (P<0.001). Eleven patients from group A (10.6%) and 78 (61.4%) from group B were seronegative for all hepatitis B virus markers (P<0.001). Only 3.8% (4/103) of group A patients and 16.5% (21/127) of group B had vaccination-induced protective antibody levels (anti-HBs) against hepatitis B (P=0.02). The majority of patients were infected with hepatitis C virus genotype-3 (64.7% from group A vs 56.7% from group B, P=0.42). The percentages of patients infected with genotype-1 were also comparable in both groups (15.5% from group A vs 30.8% from group B, P=0.09). A significantly higher percentage of group A patients were infected with genotype-4 (19.7%) than those in group B (4.9%, P=0.02). CONCLUSION The serological profile of hepatitis B virus infection among Greek hepatitis C virus-infected injecting drug users is changing. The proportion of successfully vaccinated hepatitis B virus injecting drug users, although significantly higher than the previous decades, is still relatively low. Vaccination policy in this high-risk group for viral hepatitis is urgently needed.
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Affiliation(s)
- Ioannis S Elefsiniotis
- Department of Internal Medicine, Hepatology Unit, Hippokration Hospital, Athens, Greece.
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Bialek SR, Terrault NA. The changing epidemiology and natural history of hepatitis C virus infection. Clin Liver Dis 2006; 10:697-715. [PMID: 17164113 DOI: 10.1016/j.cld.2006.08.003] [Citation(s) in RCA: 76] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Injection drug use remains the predominant mode of transmission of hepatitis C virus (HCV) infection. Growing numbers of persons who have been chronically infected with HCV for 20 or more years are coming to medical attention and are at risk for serious complications of chronic infection, including cirrhosis and hepatocellular carcinoma. Factors linked with the development of advanced fibrosis and cirrhosis include age at infection, duration of infection, heavy alcohol use, coinfections with HIV or hepatitis B virus, and male sex. Emerging risk factors for disease progression include steatosis, insulin resistance (and factors associated with the metabolic syndrome), and host genetics.
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Affiliation(s)
- Stephanie R Bialek
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, USA
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McKillop IH, Moran DM, Jin X, Koniaris LG. Molecular pathogenesis of hepatocellular carcinoma. J Surg Res 2006; 136:125-35. [PMID: 17023002 DOI: 10.1016/j.jss.2006.04.013] [Citation(s) in RCA: 85] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2006] [Revised: 04/04/2006] [Accepted: 04/11/2006] [Indexed: 12/13/2022]
Abstract
Hepatocellular carcinoma (HCC) is one of the most common life-threatening malignancies in the world. This cancer generally arises within the boundaries of well-defined causal factors, of which viral hepatitis infection, aflatoxin exposure, chronic alcohol abuse, and nonalcoholic steatohepatitis are the major risk factors. Despite the identification of these etiological agents, hepatocarcinogenesis remains poorly understood. The molecular mechanisms leading to the development of HCC appear extremely complex and only recently have begun to be elucidated. Currently, surgical resection or liver transplantation offer the best chance of cure for the patient with HCC; however, these therapies are hindered by inability of many of these patients to undergo liver resection, by tumor recurrence and by donor shortages. A lack of suitable therapeutic strategies has led to a greater focus on prevention of HCC using antiviral agents and vaccination. Overall, the current outlook for patients with HCC is bleak; however, a better understanding of the molecular and genetic basis of this cancer should lead to the development of more efficacious therapies.
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Affiliation(s)
- Iain H McKillop
- Department of Biology, University of North Carolina at Charlotte, Charlotte, North Carolina 28223, USA.
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Hajiani E, Hashemi J, Masjedizadeh R, Shayesteh AA, Idani E, Rajabi T. Seroepidemiology of hepatitis C and its risk factors in Khuzestan Province, South-West of Iran: A case-control study. World J Gastroenterol 2006; 12:4884-7. [PMID: 16937474 PMCID: PMC4087626 DOI: 10.3748/wjg.v12.i30.4884] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [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: To evaluate possible risk factors for the spread of hepatitis C infection and to analyze the characteristics of the epidemiological and clinical patterns among the patients with hepatitis C infection.
METHODS: During a five-year period a cross-sectional study was conducted among HCV positive individuals referred to the Ahwaz JundiShapour University Hospitals (AJSUH) and Hepatitis Clinic from 1 Sept 1999 to 1 Sept 2003. The control group consisted of first time blood donors referred to the Regional Blood Transfusion organization. Enzyme-linked immunosorbent assay and recombinant immunoblot assay anti-hepatitis C virus (HCV) tests were performed for two groups. Positive serum specimens were retested using polymerase chain reaction (PCR) for HCV RNA. Risk factors were evaluated using a questionnaire. Reported risk factors among infected subjects (“HCV-positive”) were compared to those of subjects never exposed (“HCV-negative”) to HCV.
RESULTS: A total of 514 subjects were studied for HCV, of which 254 were HCV-positive and 260 HCV-negative donors comprised the control group. Mean age of the patients was 28.4 (Std 15.22) years. HCV-positive subjects were more likely to be of male gender (63% versus 37%). Transfusion 132 (52%), non-intravenous (n-iv) drug abuse and iv drug abuse 37 (14.5%), haemodialysis 25 (10%), receiving wounds at war and extramarital sexual activities (2.4%), tattooing (3.6%) were found to be independent risk factors of being HCV-positive. No apparent risk factors could be demonstrated in 29 (11.2%) of the positive cases.
CONCLUSION: Our data indicate that a history of transfusion and iv drug abuse and haemodialysis are important risk factors for HCV infection in our area and that more careful pretransfusion screening of blood for anti-HCV must be introduced in our blood banks. Improvements in certain lifestyle patterns, and customs in this area may be essential to prevent transmission of the infection.
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Affiliation(s)
- Eskandar Hajiani
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Golestan Hospital, Ahwaz Jundishapur University of Medical Sciences, Ahwaz, PO Box 89, Ahwaz, Iran.
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Abstract
Combination therapy with polyethylene glycosylated IFN-alpha2a or IFN-alpha2b and ribavirin is currently the standard therapy for chronic hepatitis C. However, even with this therapy, hepatitis C virus cannot be eradicated in 50% of patients with refractory chronic hepatitis C. In addition, withdrawal or dose reduction occurs in approximately 40% of patients due to adverse effects. This treatment is also a contraindication in some patients, such as in patients with coexisting diseases or in elderly patients. For these patients, standard IFN-alpha monotherapy is even safer and more effective. In patients with chronic hepatitis C, IFN-alpha monotherapy results in a significant increase in the cumulative survival rate by suppressing the progression to hepatocellular carcinoma or liver failure. In addition, other efficacious therapeutic regimens have been employed, such as prolonged administration of standard IFN-alpha in elderly patients; prolonged low-dose continuous administration in patients with decompensated cirrhosis or hepatocellular carcinoma postoperative patients; and combination therapy with 5-fluorouracil and standard IFN-alpha for advanced hepatocellular carcinoma. Monotherapy with standard IFN-alpha should thus be recognised as one of the important therapeutic strategies for chronic hepatitis C.
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Affiliation(s)
- Mitsuhiko Moriyama
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-Kamimachi, Itabashi-ku, Tokyo 173-8610, Japan.
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Moeremans K, Warie H, Annemans L. Assessment of the economic value of the INTERCEPT blood system in Belgium. Transfus Med 2006; 16:17-30. [PMID: 16480436 DOI: 10.1111/j.1365-3148.2006.00644.x] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Emerging pathogens continue to threaten blood safety, requiring novel safety approaches. INTERCEPT Blood System for platelets (IBSP) inactivates pathogens, aiming at eliminating the risk of transmitting current and emerging pathogens. The objective was to evaluate the incremental cost-effectiveness ratio (ICER) for IBSP in Belgium. A decision model comparing a 'world with IBSP' to a 'world without IBSP' calculates lifetime costs and 'quality adjusted life years' (QALYs) following platelet transfusion in different indications. Disease-specific life expectancy and consequences of transfusion-transmitted infections were obtained from literature. Transfusion safety and costs were obtained from official sources. Hepatitis C virus-like emerging pathogen was simulated. A wide range of ICERs was observed, highly sensitive to the risk of emerging pathogen trans- mission, underlying disease and age. In the most conservative approach, ICER ranged from 3,459,201 Euro/QALY in absence of emerging pathogen to 195,364 Euro/QALY. The mean threshold of emerging infection risk for IBSP dominance (saving money and producing health gains) ranged from 1/1,079 to 1/2,858 transfusions. Considering the high value authorities appear to place on preventing accidental injury, and ICER of recent implementations in transfusion medicine (NAT: up to 2.3 million Euro per lifeyear), IBSP can be considered cost-effective, taking into account the potential risk of emerging pathogens.
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Affiliation(s)
- K Moeremans
- HEDM, Health economics and Disease Management, Brussels, Belgium.
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Chen SL, Morgan TR. The natural history of hepatitis C virus (HCV) infection. Int J Med Sci 2006; 3:47-52. [PMID: 16614742 PMCID: PMC1415841 DOI: 10.7150/ijms.3.47] [Citation(s) in RCA: 515] [Impact Index Per Article: 27.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2005] [Accepted: 03/06/2006] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) is a leading cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma, as well as the most common indication for liver transplantation in many countries. Although the incidence of hepatitis C infection has dramatically decreased during the past decade, the worldwide reservoir of chronically infected persons is estimated at 170 million, or 3% of the global population. There is much controversy surrounding the natural history of hepatitis C infection. The rate of chronic HCV infection is affected by a person's age, gender, race, and viral immune response. Approximately 75%-85% of HCV-infected persons will progress to chronic HCV infection, and are at risk for the development of extrahepatic manifestations, compensated and decompensated cirrhosis, and hepatocellular carcinoma (HCC). The rate of progression to cirrhosis is highly variable, and is influenced by several factors, including the amount of alcohol consumption, age of initial HCV infection, degree of inflammation and fibrosis on liver biopsy, HIV and HBV coinfection, and comordid conditions. An estimated 10%-15% of HCV-infected persons will advance to cirrhosis within the first 20 years. Persons with cirrhosis are at increased risk of developing HCC. An understanding of the natural history of hepatitis C is essential to effectively manage, treat, and counsel individuals with HCV infection.
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Affiliation(s)
- Stephen L. Chen
- 1. Gastroenterology Section, VA Medical Center, Long Beach, California
- 2. Division of Gastroenterology and Hepatology, University of California-Irvine, Irvine, California
| | - Timothy R. Morgan
- 1. Gastroenterology Section, VA Medical Center, Long Beach, California
- 2. Division of Gastroenterology and Hepatology, University of California-Irvine, Irvine, California
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Elefsiniotis IS, Hero B, Mariolis A, Pantazis KD, Fotos NV, Ketikoglou I, Saroglou G. Serological profile of HBV infection and liver histopathology among injecting drug users with chronic HCV infection in Greece. Eur J Intern Med 2005; 16:496-500. [PMID: 16275544 DOI: 10.1016/j.ejim.2005.05.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2004] [Revised: 04/29/2005] [Accepted: 05/26/2005] [Indexed: 10/25/2022]
Abstract
BACKGROUND The aim of this study was to evaluate the serological status of HBV infection and liver histology in chronic HCV-infected injecting drug users (IDUs) and to correlate them with the possible time of infection and the principal HCV genotype. METHODS Some 130 prior IDUs with chronic HCV infection were consecutively evaluated for the serological status of HBV infection. Fifty-eight (44.62%) reported intravenous drug use beginning before 1992 (group A) and 72 (55.38%) after 1992 (group B). HCV genotyping was available in 86 patients (PCR). Liver biopsy was performed in 48 patients (Ishak scoring system). There was no available data about alcohol consumption in the study population. Statistical analysis was based on the t-test and the chi(2) test (p<0.05). RESULTS Some 82.8% of group A patients had previous HBV infection, whereas only 22.2% of group B patients did (p<0.001). Among group A patients, 10.3% were HBV-seronegative whereas 61.1% of group B patients were (p<0.001). Only 3.4% of group A patients were HBV-vaccinated compared to 16.7% in group B (p=0.016). HCV genotype was not associated with HBV serological status. No significant differences were detected in age, sex, possible time of infection, HBV serological status, or HCV genotype among those with higher vs. lower total grading scores. Seventy-five percent of patients had mild or no detectable fibrosis unrelated to the possible period of infection, the HBV serological status, and the HCV genotype. CONCLUSIONS The serological profile of HBV infection is changing among Greek chronic HCV-infected IDUs, while the percentages of successfully HBV-vaccinated IDUs are relatively low. Severe liver disease is an uncommon finding in these patients, irrespective of the possible time of infection, the HBV serological status, and the HCV genotype.
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Yeh MM, Buskell ZJ, Seeff LB, Strader D, Wright EC, Goodman ZD. More severe parenchymal injury in chronic hepatitis C acquired by recent injection drug use. J Clin Gastroenterol 2005; 39:722-7. [PMID: 16082284 DOI: 10.1097/01.mcg.0000173852.70419.21] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
OBJECTIVE Histologic liver injury is reported to be less severe in persons who acquire hepatitis C through injection drug use (IDU) than by blood transfusion. Because age correlates with histologic severity, it may be that differences between routes of acquisition reflect the younger age of most drug abusers. The early histopathologic changes of hepatitis C acquired through IDU are less defined, probably because of the lack of liver biopsy material from a cohort of patients not long after initial exposure. The availability of material from a cohort of patients who had liver biopsy for IDU-related hepatitis C in the 1970s enabled us to compare the histology with that of current patients. METHODS Liver biopsies of a group of injection drug users (n=70, all males; mean age, 27.6 years, designated as Group 1) in the 1970s cohort were compared with biopsies of patients (n=63, all males; mean age, 48 years, designated as Group 2, 23 who admitted past IDU) entering a treatment trial in 1999. All patients were positive for anti-HCV at the time of biopsy. RESULTS The histologic features of the 23 patients in Group 2 with a history of IDU did not differ significantly from the other 40 patients who denied past IDU. Using a modified Histologic Activity Index (HAI), there was no difference between Group 1 and Group 2 in portal inflammation or periportal injury. However, parenchymal (lobular) injury and inflammation was significantly (P<0.0001) greater in Group 1 than Group 2. Fibrosis was significantly (P=0.014) greater in Group 2. CONCLUSIONS The degree of parenchymal injury was greater in Group 1 than Group 2, perhaps because they were closer to the time of exposure or possibly because of a stronger immunologic response in younger patients. The degree of hepatic fibrosis was greater in Group 2, suggesting that progression with age may be the natural history of chronic hepatitis C.
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Affiliation(s)
- Matthew M Yeh
- Department of Pathology, George Washington University School of Medicine, Washington, DC, and the Department of Medicine, Veterans Affairs Medical Center, Washington, DC, USA.
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Imazeki F, Yokosuka O, Fukai K, Kawai S, Kanda T, Kojima H, Saisho H. Lower incidence of hepatic failure than hepatocellular carcinoma in Japanese patients with chronic hepatitis C. Liver Int 2005; 25:772-8. [PMID: 15998428 DOI: 10.1111/j.1478-3231.2005.01062.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
BACKGROUND Previous studies have shown that the development of hepatic failure was found more frequently than that of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C in the United States and European countries. We investigated the status in Japan in a retrospective cohort study. METHODS The incidences of HCC and hepatic failure were accessed in 459 patients with biopsy-proven C-viral chronic liver disease with a mean follow-up period of 8.9+/-3.2 years and the cause of death was also analyzed in the cohort. RESULTS HCC developed in 63 patients, 46 of 355 interferon (IFN)-treated and 17 of 104 untreated patients. In contrast, the development of hepatic failure was found in 18 patients, 12 of 355 IFN-treated and six of 104 untreated patients. HCC developed in four of 116 with sustained virological response (SVR), and hepatic failure developed in one of them. Thirty-two of 63 patients developing HCC and eight of 18 patients developing hepatic failure died. CONCLUSIONS Development of hepatic failure was less frequent than that of HCC in Japan. It is important for a favorable prognosis of patients with C viral chronic liver disease to achieve a higher SVR and thus inhibit the development of HCC in Japan.
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Affiliation(s)
- Fumio Imazeki
- Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.
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38
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Zheng Y, Ye LB, Liu J, Jing W, Timani KA, Yang XJ, Yang F, Wang W, Gao B, Wu ZH. Gene expression profiles of HeLa Cells impacted by hepatitis C virus non-structural protein NS4B. BMB Rep 2005; 38:151-60. [PMID: 15826491 DOI: 10.5483/bmbrep.2005.38.2.151] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
By a cDNA array representing 2308 signal transduction-related genes, we studied the expression profiles of HeLa cells stably transfected by Hepatitis C virus nonstructural protein 4B (HCV-NS4B). The alterations of the expression of four genes were confirmed by real-time quantitative RTPCR; and the aldo-keto reductase family 1, member C1 (AKR1C1) enzyme activity was detected in HCV-NS4B transiently transfected HeLa cells and Huh-7, a human hepatoma cell line. Of the 2,308 genes we examined, 34 were up-regulated and 56 were down-regulated. These 90 genes involved oncogenes, tumor suppressors, cell receptors, complements, adhesions, transcription and translation, cytoskeleton and cellular stress. The expression profiling suggested that multiple regulatory pathways were affected by HCV-NS4B directly or indirectly. And since these genes are related to carcinogenesis, host defense system and cell homeostatic mechanism, we can conclude that HCV-NS4B could play some important roles in the pathogenesis mechanism of HCV.
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Affiliation(s)
- Yi Zheng
- Key Laboratory of Virology, Ministry of Education, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China
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Abstract
Epidemiologic, clinical, and virologic data have shown a close association between chronic infection with hepatitis C virus (HCV) and the development of hepatocellular carcinoma (HCC). In many countries of the developed world, HCV infection accounts for more than half of the cases of HCC. HCC usually arises after 2-4 decades of infection, typically in the context of an underlying cirrhosis. Treatment of hepatitis C with interferon-alfa can lead to sustained clearance of HCV, and small prospective studies as well as larger retrospective analyses suggest that interferon therapy leads to a decrease in the incidence of HCC. Without a reliable tissue culture system or a small animal model of HCV infection, analysis of the mechanisms by which HCV leads to cancer has been difficult. Nevertheless, both in vitro expression systems and in vivo transgenic mice studies suggest that HCV has an inherent carcinogenic potential. Understanding the pathogenesis of HCV-associated HCC is important in developing effective means of prevention and treatment of this highly malignant form of cancer.
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Affiliation(s)
- T Jake Liang
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
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40
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Abstract
Emerging data indicate that the mortality rate of hepatocellular carcinoma (HCC) associated with cirrhosis is rising in some developed countries, whereas mortality from non-HCC complications of cirrhosis is decreasing or is stable. Cohort studies indicate that HCC is currently the major cause of liver-related death in patients with compensated cirrhosis. Hepatitis C virus (HCV) infection is associated with the highest HCC incidence in persons with cirrhosis, occurring twice as commonly in Japan than in the West (5-year cumulative incidence, 30% and 17%, respectively), followed by hereditary hemochromatosis (5-year cumulative incidence, 21%). In hepatitis B virus (HBV)-related cirrhosis, the 5-year cumulative HCC risk is 15% in high endemic areas and 10% in the West. In the absence of HCV and HBV infection, the HCC incidence is lower in alcoholic cirrhotics (5-year cumulative risk, 8%) and subjects with advanced biliary cirrhosis (5-year cumulative risk, 4%). There are limited data on HCC risk in cirrhosis of other causes. Older age, male sex, severity of compensated cirrhosis at presentation, and sustained activity of liver disease are important predictors of HCC, independent of etiology of cirrhosis. In viral-related cirrhosis, HBV/HCV and HBV/HDV coinfections increase the HCC risk (2- to 6-fold relative to each infection alone) as does alcohol abuse (2- to 4-fold relative to alcohol abstinence). Sustained reduction of HBV replication lowers the risk of HCC in HBV-related cirrhosis. Further studies are needed to investigate other viral factors (eg, HBV genotype/mutant, occult HBV, HIV coinfection) and preventable or treatable comorbidities (eg, obesity, diabetes) in the HCC risk in cirrhosis.
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41
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Harder J, Walter E, Riecken B, Ihling C, Bauer TM. Hepatitis C virus infection in intravenous drug users. Clin Microbiol Infect 2004; 10:768-70. [PMID: 15301685 DOI: 10.1111/j.1469-0691.2004.00934.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Intravenous drug use (IVDU) remains a major means of hepatitis C virus (HCV) transmission. In this study, 101 drug users were studied prospectively after cessation of IVDU. Of these, 75.8% were anti-HCV positive, and 71.4% had elevated levels of alanine aminotransferase. These levels decreased significantly within 1 month of IVDU cessation (p 0.02). Liver biopsies showed minimal or mild fibrosis in 32 (71%) of 45 subjects, and severe fibrosis in two (4.4%) subjects. Anti-HCV-positive intravenous drug users in this study presented with mild liver disease and variable stages of disease progression. Biochemical disease activity might be affected by IVDU.
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Affiliation(s)
- J Harder
- University Hospital, Department of Medicine II (Gastroenterology, Hepatology and Infectious Diseases), University of Freiburg, D-79106 Freiburg, Germany.
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Krahn M, Wong JB, Heathcote J, Scully L, Seeff L. Estimating the prognosis of hepatitis C patients infected by transfusion in Canada between 1986 and 1990. Med Decis Making 2004; 24:20-9. [PMID: 15005951 DOI: 10.1177/0272989x03261568] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
OBJECTIVE To develop a natural history model for chronic hepatitis C virus (HCV) infection to determine allocation of compensatory funds to Canadians who acquired HCV through the blood supply from 1986 through 1990. METHODS A Markov cohort simulation model for HCV prognosis was developed, using content experts, published data, posttransfusion look-back data, and a national survey. RESULTS The mortality rate in transfusees is high (46% at 10 years), although HCV-related deaths are rare. Only 14% develop cirrhosis at 20 years (95% confidence interval, 0%--44%), but 1 in 4 will eventually develop cirrhosis, and 1 in 8 will die of liver disease. CONCLUSIONS This unique application of Markov cohort simulation and epidemiologic methods provides a state-of-the-art estimate of HCV prognosis and has allowed compensation decisions to be based on the best available evidence.
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Affiliation(s)
- Murray Krahn
- Toronto General Hospital, ES9 408, 200 Elizabeth Street, Toronto, Ontario M5G 2C4, Canada.
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Hu KQ, Yang H, Lin YC, Lindsay KL, Redeker AG. Clinical Profiles of Chronic Hepatitis C in a Major County Medical Center Outpatient Setting in United States. Int J Med Sci 2004; 1:92-100. [PMID: 15912201 PMCID: PMC1074717 DOI: 10.7150/ijms.1.92] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2004] [Accepted: 05/05/2004] [Indexed: 12/14/2022] Open
Abstract
The estimated prevalence of hepatitis C virus (HCV) infection in the US is 1.8 %. Data are limited on the clinical profile of the disease at first presentation and dynamic follow-up of ALT level, especially in publicly-funded patients. This information is critical for optimal management of these patients. The present study is aimed to assess the clinical profiles of chronic hepatitis C (CHC) at first presentation and clinical implication of dynamic follow-up of ALT level in a county medical center setting. A total of 294 patients were selected from the population consecutively evaluated in the Hepatitis Clinic at Los Angeles County-USC Medical Center between Jan. 1990 and Dec. 1998. Ethnicity of the patients was Hispanics-49.0%, Caucasian-28.6%, African American-13.6%, and Asian-8.8%. Risk factors were identifiable in 84.0% of patients, and injection drug use (IDU) represented the leading risk factor for HCV acquisition (47.4%). History of alcoholism was present in 39.1%. The initial clinical diagnoses were chronic hepatitis 76.9%; compensated cirrhosis 20.4%; and decompensated cirrhosis 2.7%. Elevation of ALT, alpha fetoprotein (AFP), ferritin, and anti-nuclear antibody (ANA) titer were seen in 219/294 (74.5%), 60/194 (30.9%), 20/83 (24.1%), and 35/97 (36.1%) patients, respectively. Anti-HBc (total) test was positive in 65/129 (50.5%) patients. The presence of cirrhosis was significantly associated with age greater than 55 years at entry, female gender, non-African American ethnicity, history of transfusion, lower level of albumin and elevated level of AFP. Longitudinal observation of ALT changes in 178 patients who had neither evidence of cirrhosis at entry nor received interferon treatment showed persistently normal, intermittently or persistently elevated ALT level in 15.2%, 38.3%, and 46.6% patients, respectively. The frequency of developing clinical evidence of cirrhosis during follow-up was significantly higher in patients with persistently (16.0%) or intermittently (7.0%) elevated ALT than that in patients with persistently normal ALT (4.0%). In conclusion, the present study analyzed the clinical profiles of CHC, assessed risk factors for developing cirrhosis, and demonstrated the clinical value of dynamic follow-up of ALT level in a cohort of publicly-funded patients. These data have major implications in designing optimal strategies for disease management, antiviral therapy, and screening for hepatocellular carcinoma in patients with CHC.
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Affiliation(s)
- Ke-Qin Hu
- 1 Division of Gastroenterology and Hepatology, University of California, Irvine, College of Medicine, Orange, CA, USA
| | - Huiying Yang
- 2 Division of Medical Genetics, Cedars-Sinai Medical Center/UCLA, Los Angeles, CA, USA
| | - Ying-Chao Lin
- 2 Division of Medical Genetics, Cedars-Sinai Medical Center/UCLA, Los Angeles, CA, USA
| | - Karen L Lindsay
- and 3 Division of GI/Liver, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Allan G Redeker
- and 3 Division of GI/Liver, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
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Casiraghi MA, De Paschale M, Romanò L, Biffi R, Assi A, Binelli G, Zanetti AR. Long-term outcome (35 years) of hepatitis C after acquisition of infection through mini transfusions of blood given at birth. Hepatology 2004; 39:90-6. [PMID: 14752827 DOI: 10.1002/hep.20030] [Citation(s) in RCA: 101] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Long-term follow up studies of hepatitis C virus (HCV) infection rarely exceed 20-25 yr. We studied the outcome of HCV infection in 35-yr-old adults infected at birth (1968) through mini transfusions of blood. A retrospective-prospective study was carried out. The cohort included 31 individuals who were given mini blood transfusions (21-30 ml) collected from a donor subsequently revealed to be HCV infected. At enrollment (1998), 18 of 31 (58.1%) recipients had anti-HCV antibody and 16 (88.9%) of them were HCV-RNA positive. All viremic recipients and the infectious donor had the same genotype 1b. Sequence analysis of E1/E2 and NS5b regions, coupled with phylogenetic analysis, indicated that HCV isolates from donor/recipients were linked. Eleven of the 16 viremic recipients gave consent to liver biopsy. Nine had no fibrosis or mild portal fibrosis and 2 had either discrete (Ishak's staging 3) or marked (Ishak's staging 4) fibrosis. During the prospective follow-up period (1998-2003), 2 patients were given therapy, one of whom achieved sustained clinical and virologic response. A second biopsy, performed in 5 patients at a 5 yr interval, revealed no substantial modifications in 4 cases and progression from absence of fibrosis to mild portal fibrosis in the fifth. In conclusion, taking into account the limited study sample, these findings suggest that HCV infection acquired early in life shows a slow progression and mild outcome during the first 35 yr of infection.
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Abstract
1. Hepatitis C is a global health problem affecting over 170 million people worldwide. 2. There is wide geographic variation in both prevalence and genotype distribution of hepatitis C virus on a global level. 3. Most hepatitis C virus is spread parenterally, either through intravenous drug use or, in lesser-developed countries, through blood contamination during medical procedures. 4. Hepatitis C is a leading cause of end-stage liver disease and hepatocellular carcinoma. 5. Despite a declining incidence of new infections, the burden of disease, both in terms of mortality and in terms of cost, is expected to increase over the next decade.
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Affiliation(s)
- Robert S Brown
- Department of Medicine, Columbia University College of Physicians & Surgeons, and Center for Liver Disease and Transplantation, New York-Presbyterian Hospital, New York, NY 10032, USA.
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46
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Hiraoka T, Katayama K, Tanaka J, Ohno N, Joko K, Komiya Y, Kumagai J, Mizui M, Hino K, Miyakawa Y, Yoshizawa H. Lack of epidemiological evidence for a role of resolved hepatitis B virus infection in hepatocarcinogenesis in patients infected with hepatitis C virus in Japan. Intervirology 2003; 46:171-6. [PMID: 12867755 DOI: 10.1159/000071458] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2003] [Accepted: 03/24/2003] [Indexed: 11/19/2022] Open
Abstract
OBJECTIVE The role of resolved hepatitis B virus (HBV) infection in promoting hepatocellular carcinoma (HCC) in patients infected with hepatitis C virus (HCV) in Japan was evaluated by epidemiological surveys. METHODS Antibody to hepatitis B core (anti-HBc) was determined in age-matched blood donors, and the frequency was compared with that in patients with HCV-associated HCC in Japan. RESULTS Anti-HBc was detected significantly more frequently in the blood donors with than without antibody to HCV (anti-HCV; 76/135 or 56.3% vs. 65/255 or 25.5%, p < 0.001). In the patients with HCV-associated HCC, anti-HBc was detected in 109 of 202 (54.0%), which was comparable to the frequency in anti-HCV-positive blood donors (56.3%). Among the blood donors with anti-HCV, the prevalence of anti-HBc was no different between those with and without HCV RNA in serum (40/77 or 51.9% vs. 36/58 or 62.1%). CONCLUSIONS The individuals of an age with high cancer frequency (>or=40 years) in Japan would have been exposed to HBV frequently (>50%), whether or not they have developed HCV-associated HCC. Despite repeated assertions in the literature, no epidemiological evidence was obtained for a role of past HBV infection in hepatocarcinogenesis in patients infected with HCV in Japan.
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Affiliation(s)
- Tetsuro Hiraoka
- Department of Epidemiology and Control of Infectious Diseases, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan
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Hartman C, Berkowitz D, Rimon N, Shamir R. The effect of early treatment in children with chronic hepatitis. J Pediatr Gastroenterol Nutr 2003; 37:252-7. [PMID: 12960645 DOI: 10.1097/00005176-200309000-00010] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND The aim of this study was to compare the efficacy of interferon alpha (IFN) or IFN and ribavirin (IFN+RIB) combination therapy in children with chronic hepatitis C (CHC). Most children were infected during treatment for pediatric malignancies. PATIENTS AND METHODS We reviewed the charts of 20 patients (11 boys and 9 girls) aged 10.6 +/- 3.7 years with CHC who were treated between 1995 and 2001. Seven patients diagnosed with CHC before 1998 were treated with 3 million units of IFN three times weekly for 6 to 12 months. Thirteen children diagnosed after 1998 were treated with 3 million units of IFN three times weekly plus 15 mg/kg of ribavirin daily for 6 months (IFN+RIB). RESULTS Demographic and clinical characteristics were not different between the two treatment groups. A sustained complete response defined as serum alanine aminotransferase normalization and hepatitis C virus RNA clearance at 6 and 12 months after termination of treatment occurred in three of seven children (43%) treated with IFN monotherapy compared with 7 of 12 children (54%) in the group treated with IFN+RIB combination therapy (not significant). The only difference between responders and nonresponders was the duration of infection before the initiation of therapy, which was significantly shorter in responders (1 +/- 0.3 vs. 5.6 +/- 2.2; P = 0.001). CONCLUSIONS In this small cohort of children with CHC, early initiation of antiviral treatment was associated with a sustained response rate independent of treatment type. Regular follow-up of children at risk of acquiring hepatitis C virus infection should assist in the early diagnosis. Early initiation of antiviral treatment may improve the rate of sustained response.
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Affiliation(s)
- Corina Hartman
- Division of Pediatric Gastroenterology and Nutrition, Meyer Children's Hospital of Haifa, Haifa, Israel
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Dore GJ, Freeman AJ, Law M, Kaldor JM. Natural History Models for Hepatitis C-Related Liver Disease: Different Disease Progression Parameters for Different Settings. Antivir Ther 2003. [DOI: 10.1177/135965350300800502] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
An understanding of the natural history of hepatitis C virus (HCV) infection has improved in recent years. Estimates of liver disease progression among people with chronic hepatitis C have been developed from various study populations, including liver clinics, post-transfusion hepatitis C cohorts and community-based cohorts. These estimates can be used in hepatitis C natural history models; however, they need to be matched to differing requirements. Estimation and projection of liver disease burden at the population level requires estimates of HCV prevalence and incidence, and disease progression among all people with chronic hepatitis C. Liver disease progression based on community cohorts would appear the most appropriate for a population level model. In contrast, models that examine the cost-effectiveness of antiviral therapy for people with chronic hepatitis C require disease progression estimates from the treatment setting. Further models are required to determine individual prognosis and should be based on an assessment of cofactors for liver disease progression.
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Affiliation(s)
- Gregory J Dore
- National Centre in HIV Epidemiology and Clinical Research, The University of New South Wales, Sydney, Australia
| | - Anthony J Freeman
- National Centre in HIV Epidemiology and Clinical Research, The University of New South Wales, Sydney, Australia
| | - Matthew Law
- National Centre in HIV Epidemiology and Clinical Research, The University of New South Wales, Sydney, Australia
| | - John M Kaldor
- National Centre in HIV Epidemiology and Clinical Research, The University of New South Wales, Sydney, Australia
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Serra MA, Rodríguez F, del Olmo JA, Escudero A, Rodrigo JM. Influence of age and date of infection on distribution of hepatitis C virus genotypes and fibrosis stage. J Viral Hepat 2003; 10:183-8. [PMID: 12753336 DOI: 10.1046/j.1365-2893.2003.00372.x] [Citation(s) in RCA: 39] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The objective of this study was to assess the influence of age and date of acquisition of hepatitis C virus (HCV) infection on the distribution of genotypes and the progression of fibrosis in HCV-infected patients who were born in Spain and had their habitual place of residence in this country. Genotypic analysis was performed in 375 patients in whom it was possible to establish the year of HCV infection because the mode of transmission was known (transfusion, injection drug use, blood donor, or epidemic outbreak). In 298 patients with liver biopsy, fibrosis stage was related to age at infection, duration of infection, alcohol consumption, and HCV genotype. HCV subtype 1b was almost exclusively detected among transfusion recipients, but the onset of intravenous drug addiction was associated with the introduction of HCV genotypes other than 1b among injecting users with subsequent spread to other exposure risk groups. Fibrosis progression was influenced by alcohol consumption, increased duration of infection, and older age at infection. In summary, spread of intravenous drug use determined HCV infection by genotypes other than 1b. The risk of fibrosis progression was influenced more by age at viral acquisition and alcohol consumption than by the infecting genotype.
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Affiliation(s)
- M A Serra
- Service of Hepatology, Hospital Clínico Universitario, Facultad de Medicina, Avda. Blasco Ibáñez 15, E-46010 Valencia, Spain.
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Florese RH, Nagano-Fujii M, Iwanaga Y, Hidajat R, Hotta H. Inhibition of protein synthesis by the nonstructural proteins NS4A and NS4B of hepatitis C virus. Virus Res 2002; 90:119-31. [PMID: 12457968 DOI: 10.1016/s0168-1702(02)00146-6] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Possible inhibitory effects of hepatitis C virus (HCV) proteins on cellular protein synthesis were analyzed using transient expression system. The core protein, the nonstructural protein 4A (NS4A) and NS4B, but not NS3, NS5A or NS5B, inhibited p21/Waf1 expression post-transcriptionally. Further analysis revealed that the inhibition by NS4A and NS4B was mediated at least partly, if not entirely, at the translation level. NS4A-mediated translational inhibition was counteracted to some extent by NS3 co-expressed either in trans or cis. Co-expression of NS4A and NS4B exerted an additive effect on the translational inhibition. The N-terminal two-thirds of NS4A (amino acids 1-40) was shown to be involved in the translational inhibition. We also tested possible inhibitory effects of NS4A and NS4B on synthesis of other cellular proteins in parallel with p21/Waf1. NS4A and NS4B inhibited p21/Waf1 most strongly, followed by RNase L, p53, a C-terminally truncated form of CREB-RP and 2'-5' oligoadenylate synthetase. p21/Waf1, RNase L and p53 are known to have the PEST (proline-glutamic acid-serine-threonine) motif with relatively high scores in their sequences and considered to be sensitive to intracellular degradation. Taken together, our results suggest that NS4A and NS4B each mediate translational inhibition and, probably, increased degradation of certain cellular proteins.
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Affiliation(s)
- Ruth H Florese
- Department of Microbiology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan
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