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1
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Deep A, Swaroop S, Dubey D, Rawat A, Verma A, Baisya B, Parihar R, Goel A, Rungta S. The metabolic fingerprint of chronic hepatitis C progression: Metabolome shifts and cutting-edge diagnostic options. J Mol Recognit 2024; 37:e3066. [PMID: 37916582 DOI: 10.1002/jmr.3066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 09/23/2023] [Accepted: 10/12/2023] [Indexed: 11/03/2023]
Abstract
Hepatitis C virus infection causes chronic diseases such as cirrhosis and hepatocellular carcinoma. Metabolomics research has been shown to be linked to pathophysiologic pathways in liver illnesses. The aim of this study was to investigate the serum metabolic profile of patients with chronic hepatitis C (CHC) infection and to identify underlying mechanisms as well as potential biomarkers associated with the disease. Nuclear magnetic resonance (NMR) was used to evaluate the sera of 83 patients with CHC virus and 52 healthy control volunteers (NMR). Then, multivariate statistical analysis was used to find distinguishing metabolites between the two groups. Sixteen out of 40 metabolites including include 3-HB, betaine, carnitine, creatinine, fucose, glutamine, glycerol, isopropanol, lysine, mannose, methanol, methionine, ornithine, proline, serine, and valine-were shown to be significantly different between the CHC and normal control (NC) groups (variable importance in projection >1 and p < 0.05). All the metabolic perturbations in this disease are associated with pathways of Glycine, serine, and threonine metabolism, glycerolipid metabolism, arginine and proline metabolism, aminoacyl-tRNA biosynthesis, cysteine and methionine metabolism, alanine, aspartate, and glutamate metabolism. Multivariate statistical analysis constructed using these expressed metabolites showed CHC patients can be discriminated from NCs with high sensitivity (90%) and specificity (99%). The metabolomics approach may expand the diagnostic armamentarium for patients with CHC while contributing to a comprehensive understanding of disease mechanisms.
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Affiliation(s)
- Amar Deep
- Department of Medical Gastroenterology, KGMU, Lucknow, India
- Experimental and Public Health Laboratory, Department of Zoology, Lucknow University, Lucknow, India
| | - Suchit Swaroop
- Experimental and Public Health Laboratory, Department of Zoology, Lucknow University, Lucknow, India
| | | | - Atul Rawat
- Centre of Biomedical Research, Lucknow, India
| | - Ajay Verma
- Centre of Biomedical Research, Lucknow, India
| | | | | | - Amit Goel
- Department of Medical Gastroenterology, SGPGIMS, Lucknow, India
| | - Sumit Rungta
- Department of Medical Gastroenterology, KGMU, Lucknow, India
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2
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Impact of COVID-19 fear on Hepatitis C management. JOURNAL OF SURGERY AND MEDICINE 2023. [DOI: 10.28982/josam.7697] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/04/2023] Open
Abstract
Background/Aim: Hepatitis C virus (HCV) infection, a major cause of cirrhosis worldwide, is the most common cause of cirrhosis and hepatocellular carcinoma in Turkey. Today, HCV infection can be treated effectively and safely using direct-acting antiviral drugs, and therefore, the World Health Organization has announced elimination targets by 2030. During the pandemic, many social and personal restrictions were applied for fear of increasing the prevalence of coronavirus disease 2019 (COVID-19) infection. Here we investigate the effects of these restrictions on managing HCV infection in internal medicine departments that deal with both infections.
Methods: Patients who applied to the internal medicine departments of our hospital and tested for anti-HCV between 11 March 2020 and 09 April 2022, which was the time interval when official restrictions were applied in Turkey during the COVID-19 pandemic, were included in the study. Patients who were not tested for anti-HCV were excluded from the study. The study was planned as a retrospective cohort study, and patients’ files tested for anti-HCV were scanned. Anti-HCV positivity, HCV RNA PCR testing, and treatment status in HCV RNA-positive patients were evaluated.
Results: During the official pandemic period when social restrictions were applied, anti-HCV positivity was revealed in 400 (1.9%) of 21,501 patients for whom anti-HCV tests were performed in internal medicine departments. HCV RNA was not tested in 64 of 400 patients with positive anti-HCV test (16%), and 83 (24.7%) of 336 patients tested for HCV RNA were found to be positive. It was determined that 17 (20.5%) of the HCV RNA-positive patients did not receive antiviral treatment.
Conclusion: In studies conducted in Turkey in the pre-pandemic period, it was determined that HCV RNA was not tested in approximately half of the anti-HCV-positive patients, while this rate was found to be only 16% during the pandemic period. This can be explained by the fact that patients infected with the COVID-19 virus were mostly followed-up by internal medicine clinics, where the awareness of viral hepatitis was high. It was determined that 20.5% of the patients with positive HCV RNA PCR tests remained untreated. This finding suggested that the social and personal restrictions applied during the pandemic led to patient follow-up and treatment disruptions.
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Nagra N, Kozarek RA, Burman BE. Therapeutic Advances in Viral Hepatitis A-E. Adv Ther 2022; 39:1524-1552. [PMID: 35220557 DOI: 10.1007/s12325-022-02070-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 01/31/2022] [Indexed: 11/25/2022]
Abstract
Viral hepatitis remains a significant global health problem. All forms of viral hepatitis A through E (A-E) can lead to acute symptomatic infection, while hepatitis B and C can lead to chronic infection associated with significant morbidity and mortality related to progression to cirrhosis, end-stage-liver disease, and liver cancer. Viral hepatitis occurs worldwide, though certain regions are disproportionately affected. We now, remarkably, have highly effective curative regimens for hepatitis C, and safe and tolerable medications to suppress hepatitis B activity, and to prevent liver damage and slow disease progression. We have effective vaccines for hepatitis A and B which provide long-lasting immunity, while improved sanitation and awareness can curb outbreaks of hepatitis A and E. However, more effective and available preventive and curative strategies are needed to achieve global eradication of viral hepatitis. This review provides an overview of the epidemiology, transmission, diagnosis, and clinical features of each viral hepatitis with a primary focus on current and future therapeutic and curative options.
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Affiliation(s)
- Navroop Nagra
- Department of Gastroenterology, University of Louisville, Louisville, KY, 40202, USA
| | - Richard A Kozarek
- Center for Digestive Health, Virginia Mason Franciscan Health, 1100 9th Ave., Seattle, WA, 98101, USA
| | - Blaire E Burman
- Center for Digestive Health, Virginia Mason Franciscan Health, 1100 9th Ave., Seattle, WA, 98101, USA.
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4
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Chandra Deb L, Hove H, Miller TK, Pinks K, Njau G, Hagan JJ, Jansen RJ. Epidemiology of Hepatitis C virus infection among incarcerated populations in North Dakota. PLoS One 2022; 17:e0266047. [PMID: 35349606 PMCID: PMC8963564 DOI: 10.1371/journal.pone.0266047] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Accepted: 03/12/2022] [Indexed: 12/09/2022] Open
Abstract
This retrospective cohort study was conducted to determine the prevalence of HCV infections among individuals incarcerated in a state prison system and identify potential contributing factors to HCV infection. North Dakota Department of Corrections and Rehabilitation (NDDOCR) data from 2009 to 2018 was used and period prevalence was calculated for this 10-year time period. The period prevalence of HCV infection was (15.13% (95% CI 14.39–15.90) with a marginally significant (p-value: 0.0542) increasing linear trend in annual prevalence over this period. Multivariate logistic regression analysis was used to identify risk factors associated with HCV infection. The main significant independent risk factors for HCV infection in this incarcerated population were age >40 years [OR: 1.78 (1.37–2.32)]; sex [OR: 1.21 (1.03–1.43)]; race/ethnicity [OR: 1.97 (1.69–2.29)]; history of intravenous drug use (IVDU) [OR: 7.36 (6.41–8.44)]; history of needle or syringe sharing [OR: 7.57 (6.62–8.67)]; and alcohol use [OR: 0.87 (0.77–0.99)]. Study limitations include uncollected information on sexual history, frequency or duration of injection drug use and blood transfusion history of the incarcerated population. Considering the high prevalence of HCV infection and its associated risk factors, it is important to implement prevention programs such as syringe/needle exchanges and counsel with imprisoned IVD users.
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Affiliation(s)
- Liton Chandra Deb
- Department of Public Health, North Dakota State University, Fargo, ND, United States of America
- Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States of America
| | - Hannah Hove
- Department of Public Health, North Dakota State University, Fargo, ND, United States of America
- University of North Dakota School of Medicine & Health Sciences, Grand Forks, ND, United States of America
| | - Tracy K. Miller
- North Dakota Department of Health, Bismarck, ND, United States of America
| | - Kodi Pinks
- North Dakota Department of Health, Bismarck, ND, United States of America
| | - Grace Njau
- North Dakota Department of Health, Bismarck, ND, United States of America
| | - John J. Hagan
- North Dakota Department of Corrections and Rehabilitation, Bismarck, ND, United States of America
| | - Rick J. Jansen
- Department of Public Health, North Dakota State University, Fargo, ND, United States of America
- Genomics, Phenomics, and Bioinformatics Program, North Dakota State University, Fargo, ND, United States of America
- Center for Immunization Research and Education (CIRE), North Dakota State University, Fargo, ND, United States of America
- Center for Diagnostic and Therapeutic Strategies in Pancreatic Cancer, North Dakota State University, Fargo, ND, United States of America
- * E-mail:
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5
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Kouroumalis E, Voumvouraki A. Hepatitis C virus: A critical approach to who really needs treatment. World J Hepatol 2022; 14:1-44. [PMID: 35126838 PMCID: PMC8790391 DOI: 10.4254/wjh.v14.i1.1] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 04/14/2021] [Accepted: 12/31/2021] [Indexed: 02/06/2023] Open
Abstract
Introduction of effective drugs in the treatment of hepatitis C virus (HCV) infection has prompted the World Health Organization to declare a global eradication target by 2030. Propositions have been made to screen the general population and treat all HCV carriers irrespective of the disease status. A year ago the new severe acute respiratory syndrome coronavirus 2 virus appeared causing a worldwide pandemic of coronavirus disease 2019 disease. Huge financial resources were redirected, and the pandemic became the first priority in every country. In this review, we examined the feasibility of the World Health Organization elimination program and the actual natural course of HCV infection. We also identified and analyzed certain comorbidity factors that may aggravate the progress of HCV and some marginalized subpopulations with characteristics favoring HCV dissemination. Alcohol consumption, HIV coinfection and the presence of components of metabolic syndrome including obesity, hyperuricemia and overt diabetes were comorbidities mostly responsible for increased liver-related morbidity and mortality of HCV. We also examined the significance of special subpopulations like people who inject drugs and males having sex with males. Finally, we proposed a different micro-elimination screening and treatment program that can be implemented in all countries irrespective of income. We suggest that screening and treatment of HCV carriers should be limited only in these particular groups.
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Affiliation(s)
- Elias Kouroumalis
- Department of Gastroenterology, University of Crete Medical School, Heraklion 71500, Crete, Greece
| | - Argyro Voumvouraki
- First Department of Internal Medicine, AHEPA University Hospital, Thessaloniki 54621, Greece
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6
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Inflammation and Liver Cell Death in Patients with Hepatitis C Viral Infection. Curr Issues Mol Biol 2021; 43:2022-2035. [PMID: 34889885 PMCID: PMC8929145 DOI: 10.3390/cimb43030139] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 11/05/2021] [Accepted: 11/11/2021] [Indexed: 01/03/2023] Open
Abstract
Hepatitis C virus (HCV)-induced liver disease contributes to chronic hepatitis. The immune factors identified in HCV include changes in the innate and adaptive immune system. The inflammatory mediators, known as "inflammasome", are a consequence of the metabolic products of cells and commensal or pathogenic bacteria and viruses. The only effective strategy to prevent disease progression is eradication of the viral infection. Immune cells play a pivotal role during liver inflammation, triggering fibrogenesis. The present paper discusses the potential role of markers in cell death and the inflammatory cascade leading to the severity of liver damage. We aim to present the clinical parameters and laboratory data in a cohort of 88 HCV-infected non-cirrhotic and 25 HCV cirrhotic patients, to determine the characteristic light microscopic (LM) and transmission electron microscopic (TEM) changes in their liver biopsies and to present the link between the severity of liver damage and the serum levels of cytokines and caspases. A matched HCV non-infected cohort was used for the comparison of serum inflammatory markers. We compared the inflammation in HCV individuals with a control group of 280 healthy individuals. We correlated the changes in inflammatory markers in different stages of the disease and the histology. We concluded that the serum levels of cytokine, chemokine, and cleaved caspase markers reveal the inflammatory status in HCV. Based upon the information provided by the changes in biomarkers the clinician can monitor the severity of HCV-induced liver damage. New oral well-tolerated treatment regimens for chronic hepatitis C patients can achieve cure rates of over 90%. Therefore, using the noninvasive biomarkers to monitor the evolution of the liver damage is an effective personalized medicine procedure to establish the severity of liver injury and its repair.
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7
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Darke J, Cresswell T, McPherson S, Hamoodi A. Hepatitis C in a prison in the North East of England: what is the economic impact of the universal offer of testing and emergent medications? J Public Health (Oxf) 2018; 38:e554-e562. [PMID: 28158850 DOI: 10.1093/pubmed/fdv178] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- Joanne Darke
- Health Protection Team, North East Public Health England Centre, Newcastle upon Tyne NE1 4WH, UK
| | - Tricia Cresswell
- Health Protection Team, North East Public Health England Centre, Newcastle upon Tyne NE1 4WH, UK
| | - Stuart McPherson
- Liver Unit, Freeman Hospital, Newcastle upon Tyne, Tyne and Wear NE7 7DN, UK
| | - Abi Hamoodi
- Health Improvement Team, North East Public Health England Centre, Newcastle upon Tyne NE15 8NY, UK
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8
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Fabrizi F, Martin P. Hepatitis C Virus Infection in Dialysis: An Emerging Clinical Reality. Int J Artif Organs 2018. [DOI: 10.1177/039139880102400302] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Affiliation(s)
- F. Fabrizi
- Division of Nephrology and Dialysis, Ospedale Maggiore Policlinico, IRCCS, Milano - Italy
| | - P. Martin
- Liver Transplant Program, Cedars-Sinai Medical Center, UCLA School of Medicine, University of California at Los Angeles, Los Angeles, California - USA
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9
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Shiffman ML. The next wave of hepatitis C virus: The epidemic of intravenous drug use. Liver Int 2018; 38 Suppl 1:34-39. [PMID: 29427493 DOI: 10.1111/liv.13647] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2017] [Accepted: 11/24/2017] [Indexed: 02/13/2023]
Abstract
The epidemic of hepatitis C virus (HCV) began in the 1960s when transmission was primarily the result of blood transfusions. By 1990, when HCV was identified and a serologic test for screening donated blood was implemented, 123 million persons had already become infected worldwide and HCV was the most common cause of cirrhosis, hepatocellular carcinoma and the most common indication for liver transplantation. Approximately 75% of persons with HCV are "baby boomers" born between the years 1945 and 1965. The number of new cases of HCV declined precipitously between 1990 and 2005. The next wave of HCV began in 2005, and transmission is primarily the result of an epidemic of intravenous drug use. New cases of HCV have increased three-fold between 2005 and 2015. Approximately 50% of persons who inject drugs (PWID) have been exposed to HCV, and 25% of these persons are under the age of 25 years. The treatment of chronic HCV in PWID has two goals; treating HCV and preventing the patient from returning to drug use and becoming reinfected. Highly effective oral antiviral agents are now available and can cure HCV in virtually all patients. Treatment can be highly effective in PWID with sustained virologic response rates similar to that observed in a non-drug-using population. Preventing the patient from returning to drug use and becoming reinfected with HCV is more difficult and will require that the medical and social problems associated with intravenous drug use be addressed and resolved.
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10
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Le AK, Zhao C, Hoang JK, Tran SA, Chang CY, Jin M, Nguyen NH, Yasukawa LA, Zhang JQ, Weber SC, Garcia G, Nguyen MH. Ethnic disparities in progression to advanced liver disease and overall survival in patients with chronic hepatitis C: impact of a sustained virological response. Aliment Pharmacol Ther 2017; 46:605-616. [PMID: 28766727 DOI: 10.1111/apt.14241] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2017] [Revised: 06/04/2017] [Accepted: 07/08/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND Chronic hepatitis C (CHC) can lead to cirrhosis and hepatocellular carcinoma (HCC). A sustained virological response (SVR) is associated with improved outcomes, however, its impact on different ethnic groups is unknown. AIM To evaluate ethnic differences in the natural history of CHC and the impact of SVR. METHODS We conducted a cohort study of 8039 consecutive adult CHC patients seen at two medical centres in California between January 1997 and June 2016. Individual chart review confirmed CHC diagnosis. RESULTS Asian and Hispanic but not African American patients had significantly higher cirrhosis and HCC incidence than Caucasians. On multivariate analysis, Hispanic ethnicity was independently associated with increased cirrhosis (adjusted HR 1.37, CI, confidence interval 1.10-1.71, P=.006) and HCC risk (adjusted HR 1.47, CI 1.13-1.92, P=.004) compared to Caucasian. Asian ethnicity had a significant association with cirrhosis (adjusted HR 1.28, CI 1.02-1.61, P=.034) and HCC risk (adjusted HR 1.29, CI 0.94-1.77, P=.025). In patients who achieved SVR, Hispanic ethnicity was no longer independently associated with cirrhosis (adjusted HR 1.76, CI 0.66-4.71, P=.26) or HCC (adjusted HR 1.05, CI 0.27-4.08, P=.94); nor was Asian ethnicity (adjusted HR 0.62, CI 0.21-1.82, P=.38 for cirrhosis; 2.01, CI 0.63-6.36, P=.24 for HCC). Similar findings were observed with overall survival among the ethnicities by SVR status. CONCLUSION Hispanic and Asian ethnicity was independently associated with increased cirrhosis and HCC risk. Achieving an SVR eliminates the ethnic disparity in liver disease progression and overall survival between Hispanic and Asian vs Caucasian CHC patients.
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Affiliation(s)
- A K Le
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - C Zhao
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA.,Department of Cirrhosis, Institute of Liver Disease, Shuguang Hospital, Shanghai, China
| | - J K Hoang
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - S A Tran
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA.,Stanford University, Palo Alto, CA, USA
| | - C Y Chang
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA.,David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
| | - M Jin
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA.,Department of Epidemiology and Biostatistics, Zhejiang University, Hangzhou, China
| | - N H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA.,Department of Medicine, University of California, San Diego, San Diego, CA, USA
| | - L A Yasukawa
- Center for Clinical Informatics, Stanford University School of Medicine, Palo Alto, CA, USA
| | - J Q Zhang
- Chinese Hospital, San Francisco, CA, USA
| | - S C Weber
- Center for Clinical Informatics, Stanford University School of Medicine, Palo Alto, CA, USA
| | - G Garcia
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - M H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
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11
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Schwarzinger M, Baillot S, Yazdanpanah Y, Rehm J, Mallet V. Contribution of alcohol use disorders on the burden of chronic hepatitis C in France, 2008-2013: A nationwide retrospective cohort study. J Hepatol 2017; 67:454-461. [PMID: 28396173 DOI: 10.1016/j.jhep.2017.03.031] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2016] [Revised: 02/14/2017] [Accepted: 03/27/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Hepatitis C virus (HCV) patients are at risk of alcohol use disorders (AUDs). We measured the contribution of AUDs on the burden of chronic HCV infection in French HCV patients. METHODS The hospital trajectory of 97,347 French HCV patients aged 18-65 in January 2008 were tracked and followed until in-hospital death or December 2013. Primary outcome was the frequency of liver-related complications. Secondary outcomes were the frequency of liver transplantation and otherwise cause-specific mortality. Adjusted odds ratios (OR), population attributable risks of AUDs and other cofactors of liver disease progression associated with HCV transmission were measured. RESULTS The 28,101 (28.9%) individuals with AUDs had the highest odds for liver-related complications (OR=7.19; 95% confidence interval [CI], 6.90 to 7.50), liver transplantation (OR=4.28; 95% CI, 3.80 to 4.82), and liver death (OR=6.20; 95% CI, 5.85 to 6.58). Alcohol rehabilitation and abstinence were associated with 60% (95% CI, 57% to 63%) and 78% (95% CI, 76% to 80%) reduction of liver-related complications, respectively. The attributable risk of AUDs was 71.8% (95% CI, 66.0 to 76.8) of 17,669 liver-related complications, 67.4% (95% CI, 61.6 to 72.4) of 1,599 liver transplantations, and 68.8% (95% CI, 63.4 to 73.5) of 6,677 liver deaths. The number of liver transplantations remained stable and the number of liver deaths increased, at a faster rate for individuals with AUDs, over the observational period. CONCLUSION In France, AUDs contributed to more than two-thirds of the burden of chronic HCV infection in young and middle-aged adults over 2008-2013. LAY SUMMARY This study tracked liver-related complications and mortality of all 97,347 young and middle-aged patients (18-65years old) discharged with chronic HCV infection from French hospitals over 2008-2013. About 30% patients were recorded with alcohol use disorders (AUDs) and had the highest odds for liver-related complications (i.e. decompensated cirrhosis and liver cancer). AUDs contributed to more than two-thirds of 1,599 liver transplantations and 6,677 liver deaths recorded in patients with chronic HCV infection over 2008-2013 in France. Alcohol rehabilitation and abstinence were associated with above a 50% risk reduction of liver-related complications. Promoting alcohol abstinence should receive high priority to reduce the burden of chronic HCV infection.
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Affiliation(s)
- Michaël Schwarzinger
- Translational Health Economics Network (THEN), Paris, France; Infection Antimicrobials Modeling & Evolution (IAME), UMR 1137, Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Paris Diderot, Sorbonne Paris Cité, France.
| | - Sylvain Baillot
- Translational Health Economics Network (THEN), Paris, France
| | - Yazdan Yazdanpanah
- Infection Antimicrobials Modeling & Evolution (IAME), UMR 1137, Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Paris Diderot, Sorbonne Paris Cité, France; Service des Maladies Infectieuses et Tropicales, Hôpital Bichat Claude Bernard, Assistance Publique - Hôpitaux de Paris, Paris, France
| | - Jürgen Rehm
- Social and Epidemiological Research Department, Centre for Addiction and Mental Health, Toronto, Canada; Addiction Policy, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada; Institute of Medical Science, University of Toronto, Faculty of Medicine, Medical Sciences Building, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada; Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Dresden, Germany
| | - Vincent Mallet
- Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Institut Pasteur, Institut National de la Santé et de la Recherche Médicale (Inserm), Unité 1223, Paris, France; Hepatology Service, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier Cochin Port-Royal, Paris, France.
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12
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Ponzetto A, Holton J, Vaira D. Letter: years of life that could be saved by preventing HCC. Aliment Pharmacol Ther 2017; 45:375-376. [PMID: 27933689 DOI: 10.1111/apt.13853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/08/2022]
Affiliation(s)
- A Ponzetto
- Department of Medical Science, University of Turin, Torino, Italy
| | - J Holton
- National Mycobacterial Reference Unit, National Mycobacterium Reference Laboratory, Abernethy Building, Institute of Cell and Molecular Science, London, UK
| | - D Vaira
- Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
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13
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Setiawan VW, Stram DO, Porcel J, Lu SC, Le Marchand L, Noureddin M. Prevalence of chronic liver disease and cirrhosis by underlying cause in understudied ethnic groups: The multiethnic cohort. Hepatology 2016; 64:1969-1977. [PMID: 27301913 PMCID: PMC5115980 DOI: 10.1002/hep.28677] [Citation(s) in RCA: 226] [Impact Index Per Article: 25.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2016] [Accepted: 05/21/2016] [Indexed: 12/14/2022]
Abstract
UNLABELLED Chronic liver disease (CLD) and cirrhosis are major sources of morbidity and mortality in the United States. Little is known about the epidemiology of these two diseases in ethnic minority populations in the United States. We examined the prevalence of CLD and cirrhosis by underlying etiologies among African Americans, Native Hawaiians, Japanese Americans, Latinos, and whites in the Multiethnic Cohort. CLD and cirrhosis cases were identified using Medicare claims between 1999 and 2012 among the fee-for-service participants (n = 106,458). We used International Classification of Diseases Ninth Revision codes, body mass index, history of diabetes mellitus, and alcohol consumption from questionnaires to identify underlying etiologies. A total of 5,783 CLD (3,575 CLD without cirrhosis and 2,208 cirrhosis) cases were identified. The prevalence of CLD ranged from 3.9% in African Americans and Native Hawaiians to 4.1% in whites, 6.7% in Latinos, and 6.9% in Japanese. Nonalcoholic fatty liver disease (NAFLD) was the most common cause of CLD in all ethnic groups combined (52%), followed by alcoholic liver disease (21%). NAFLD was the most common cause of cirrhosis in the entire cohort. By ethnicity, NAFLD was the most common cause of cirrhosis in Japanese Americans, Native Hawaiians, and Latinos, accounting for 32% of cases. Alcoholic liver disease was the most common cause of cirrhosis in whites (38.2%), while hepatitis C virus was the most common cause in African Americans (29.8%). CONCLUSIONS We showed racial/ethnic variations in the prevalence of CLD and cirrhosis by underlying etiology; NAFLD was the most common cause of CLD and cirrhosis in the entire cohort, and the high prevalence of NAFLD among Japanese Americans and Native Hawaiians is a novel finding, warranting further studies to elucidate the causes. (Hepatology 2016;64:1969-1977).
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Affiliation(s)
- Veronica Wendy Setiawan
- Department of Preventive Medicine, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA,Norris Comprehensive Cancer Center, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA
| | - Daniel O. Stram
- Department of Preventive Medicine, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA
| | - Jacqueline Porcel
- Norris Comprehensive Cancer Center, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA
| | - Shelly C. Lu
- Fatty Liver Program, Division of Digestive and Liver Diseases, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Loїc Le Marchand
- Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA
| | - Mazen Noureddin
- Fatty Liver Program, Division of Digestive and Liver Diseases, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA,Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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14
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Eyster ME, Kong L, Li M, Schreibman IR. Long term survival in persons with hemophilia and chronic hepatitis C: 40 year outcomes of a large single center cohort. Am J Hematol 2016; 91:E335-40. [PMID: 27214557 DOI: 10.1002/ajh.24427] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2016] [Revised: 05/17/2016] [Accepted: 05/19/2016] [Indexed: 12/13/2022]
Abstract
We studied the course of chronic HCV infections in a cohort of 222 persons with hemophilia (PWH) and von Willebrand disease followed at our center since 1973. Twenty two (10%) developed end stage liver disease (ESLD). Forty years after HCV infection, cumulative incidence of ESLD was 12.3% and overall survival was 45.5%. Those who were infected with HCV only (n = 100) had a survival of 75.2%, while those infected with HIV (n = 122) had a survival of 24% (P < 0.001). Survivals were significantly longer for those infected with HCV at younger age (< 15 years) compared to those infected over age 30 years (P = 0.014). Cause specific deaths for ESLD and bleeding were 8.8% and 8.3% respectively. For HIV negative subjects, the annual hazard of death from ESLD and bleeding was near zero for the first 10 years, and then rose slowly over the next 20 years to 0.4/100py for ESLD and 0.2/100py for bleeding. Sixty subjects completed 79 treatment episodes. Sustained viral response rates increased from 7/21 (33%) between 1990 and 2001, to 17/29 (58%) between 2002 and 2011, and to 27/29 (93%), since 2012 with the advent of the directly acting antiviral agents. These results confirm the very slow ESLD progression rate in HIV negative PWH. However, the risk of death from both ESLD and bleeding increases steadily with longer duration of HCV infection. More aggressive surveillance to detect those with early fibrosis is needed now that curative treatment is possible in >95% of individuals. Am. J. Hematol. 91:E335-E340, 2016. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- M. Elaine Eyster
- Department of Medicine; Division of Hematology/Oncology; Penn State Milton S. Hershey Medical Center; PO Box 850, 500 University Drive Hershey Pennsylvania
| | - Lan Kong
- Department of Public Health Sciences; Penn State Milton S. Hershey Medical Center; PO Box 850, 500 University Drive Hershey Pennsylvania
| | - Menghan Li
- Department of Public Health Sciences; Penn State Milton S. Hershey Medical Center; PO Box 850, 500 University Drive Hershey Pennsylvania
| | - Ian R. Schreibman
- Department of Medicine; Division of Gastroenterology and Hepatology; Penn State Milton S. Hershey Medical Center; PO Box 850, 500 University Drive Hershey Pennsylvania
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15
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Franchini M, Tagliaferri A, Rossetti G, Capra F, De Maria E, Pattacini C, Gandini G. The Natural History of Hepatitis C Virus Infection in Hemophiliacs. ACTA ACUST UNITED AC 2016; 6:135-42. [PMID: 27419880 DOI: 10.1080/10245332.2001.11746564] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Hepatitis C virus (HCV) infection is an important cause of morbidity and mortality in patients affected by hereditary bleeding disorders and treated with non-virus inactivated clotting factor concentrates during the 1970s. Since the onset of the infection is known (first treatment with large-pool non-virus inactivated blood products) these patients are a unique model for studying the natural history of HCV infection and associated complications. The course of Hepatitis can be accurately assessed in these patients because they are regularly followed at hemophilia centers with laboratory, clinical and instrumental tests. In this review, we briefly report the present knowledge about the natural course of HCV infection in hemophiliacs, by analyzing the prevalence of HCV infection, the genotype distribution and the risk factors involved in the progression of chronic Hepatitis into severe liver disease as cirrhosis, liver decompensation and hepatocellular carcinoma. Understanding the natural evolution of HCV infection in hemophiliacs helps us to understand better the natural history of HCV infection and to improve the treatment approach to all HCV infected patients.
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Affiliation(s)
- M Franchini
- a Servizio di Immunoematologia e Trasfusione- Centro Emofilia , Azienda Ospedaliera di Verona, Ospedale Policlinico , Via Delle Menegone 1, 37134 Verona , Italy
| | - A Tagliaferri
- b V Divisione Medica-Centro Emofilia , Azienda Ospedaliera di Parma , Parma , Italy
| | - G Rossetti
- c Servizio di Immunoematologia e Trasfusione-Centro Emofilia , Ospedale S.Chiara, Trento , Italy
| | - F Capra
- d Medicina Interna A, Dipartimento di Medicina e Sanità Pubblica , Università di Verona , Verona , Italy
| | - E De Maria
- d Medicina Interna A, Dipartimento di Medicina e Sanità Pubblica , Università di Verona , Verona , Italy
| | - C Pattacini
- b V Divisione Medica-Centro Emofilia , Azienda Ospedaliera di Parma , Parma , Italy
| | - G Gandini
- a Servizio di Immunoematologia e Trasfusione- Centro Emofilia , Azienda Ospedaliera di Verona, Ospedale Policlinico , Via Delle Menegone 1, 37134 Verona , Italy
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16
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Innes H, Hutchinson SJ, Obel N, Christensen PB, Aspinall EJ, Goldberg D, Krarup H, McDonald SA, McLeod A, Weir A, Omland LH. Liver mortality attributable to chronic hepatitis C virus infection in Denmark and Scotland--using spontaneous resolvers as the benchmark comparator. Hepatology 2016; 63:1506-16. [PMID: 26773546 DOI: 10.1002/hep.28458] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2015] [Revised: 12/07/2015] [Accepted: 01/10/2016] [Indexed: 01/10/2023]
Abstract
UNLABELLED Liver mortality among individuals with chronic hepatitis C (CHC) infection is common, but the relative contribution of CHC per se versus adverse health behaviors is uncertain. We explored data on spontaneous resolvers of hepatitis C virus (HCV) as a benchmark group to uncover the independent contribution of CHC on liver mortality. Using national HCV diagnosis and mortality registers from Denmark and Scotland, we calculated the liver mortality rate (LMR) for persons diagnosed with CHC infection (LMRchronic ) and spontaneously resolved infection (LMRresolved ), according to subgroups defined by age, sex, and drug use. Through these mortality rates, we determined subgroup-specific attributable fractions (AFs), defined as (LMRchronic - LMRresolved )/LMRchronic , and then calculated the total attributable fraction (TAF) as a weighted average of these AFs. Thus, the TAF represents the overall fraction (where 0.00 = not attributable at all; and 1.00 = entirely attributable) of liver mortality attributable to CHC in the diagnosed population. Our cohort comprised 7,005 and 21,729 persons diagnosed with HCV antibodies in Denmark and Scotland, respectively. Mean follow-up duration was 6.3-6.9 years. The TAF increased stepwise with age. It was lowest for death occurring at <45 years of age (0.21 in Denmark; 0.26 in Scotland), higher for death occurring at 45-59 years (0.69 in Denmark; 0.69 in Scotland), and highest for death at 60+years (0.92 in Denmark; 0.75 in Scotland). Overall, the TAF was 0.66 (95% confidence interval [CI]: 0.55-0.78) in Denmark and 0.55 (95% CI: 0.44-0.66) in Scotland. CONCLUSIONS In Denmark and Scotland, the majority of liver death in the CHC-diagnosed population can be attributed to CHC-nevertheless, an appreciable fraction cannot, cautioning that liver mortality in this population is a compound problem that can be reduced, but not solved, through antiviral therapy alone.
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Affiliation(s)
- Hamish Innes
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK.,Health Protection Scotland, Blood borne viruses and STIs, Glasgow, UK
| | - Sharon J Hutchinson
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK.,Health Protection Scotland, Blood borne viruses and STIs, Glasgow, UK
| | - Niels Obel
- Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Peer B Christensen
- Department of Infectious Diseases, Odense University Hospital, Odense, Denmark
| | - Esther J Aspinall
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK.,Health Protection Scotland, Blood borne viruses and STIs, Glasgow, UK
| | - David Goldberg
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK.,Health Protection Scotland, Blood borne viruses and STIs, Glasgow, UK
| | - Henrik Krarup
- Section of Molecular Diagnostics, Clinical Biochemistry, Aalborg University Hospital, Aalborg Hospital, Aalborg, Denmark
| | - Scott A McDonald
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK.,Health Protection Scotland, Blood borne viruses and STIs, Glasgow, UK
| | - Allan McLeod
- Health Protection Scotland, Blood borne viruses and STIs, Glasgow, UK
| | - Amanda Weir
- NHS, National Services Scotland, Edinburgh, UK
| | - Lars H Omland
- Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
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17
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Brothers KB, Holm IA, Childerhose JE, Antommaria AHM, Bernhardt BA, Clayton EW, Gelb BD, Joffe S, Lynch JA, McCormick JB, McCullough LB, Parsons DW, Sundaresan AS, Wolf WA, Yu JH, Wilfond BS. When Participants in Genomic Research Grow Up: Contact and Consent at the Age of Majority. J Pediatr 2016; 168:226-231.e1. [PMID: 26477867 PMCID: PMC4824174 DOI: 10.1016/j.jpeds.2015.09.020] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2015] [Revised: 07/23/2015] [Accepted: 09/04/2015] [Indexed: 01/16/2023]
Affiliation(s)
- Kyle B. Brothers
- Department of Pediatrics, University of Louisville School of Medicine
| | - Ingrid A. Holm
- Division of Genetics and Genomics and The Manton Center for Orphan Disease Research, Boston Children's Hospital; and the Department of Pediatrics, Harvard Medical School
| | | | | | | | | | - Bruce D. Gelb
- Mindich Child Health and Development Institute, Departments of Pediatrics and Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai
| | - Steven Joffe
- Department of Medical Ethics and Health Policy, University of Pennsylvania Perelman School of Medicine
| | - John A. Lynch
- Department of Communication, University of Cincinnati
| | - Jennifer B. McCormick
- Divisions of General Internal Medicine and Health Care and Policy Research, and the Mayo Biomedical Ethics Program, Mayo Clinic
| | | | - D. Williams Parsons
- Texas Children's Cancer Center and Department of Pediatrics, Baylor College of Medicine
| | | | - Wendy A. Wolf
- Division of Genetics and Genomics, Boston Children's Hospital
| | - Joon-Ho Yu
- Department of Pediatrics, University of Washington
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18
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Neuman MG, Malnick S, Maor Y, Nanau RM, Melzer E, Ferenci P, Seitz HK, Mueller S, Mell H, Samuel D, Cohen LB, Kharbanda KK, Osna NA, Ganesan M, Thompson KJ, McKillop IH, Bautista A, Bataller R, French SW. Alcoholic liver disease: Clinical and translational research. Exp Mol Pathol 2015; 99:596-610. [PMID: 26342547 DOI: 10.1016/j.yexmp.2015.09.001] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2015] [Accepted: 09/01/2015] [Indexed: 02/05/2023]
Abstract
The present review spans a broad spectrum of topics dealing with alcoholic liver disease (ALD), including clinical research, translational research, pathogenesis and therapies. A special accent is placed on alcohol misuse, as alcohol is a legally commercialized and taxable product. Drinking alcohol, particularly from a young age, is a major health problem. Alcoholism is known to contribute to morbidity and mortality. A systematic literature search was performed in order to obtain updated data (2008-2015). The review is focused on genetic polymorphisms of alcohol metabolizing enzymes and the role of cytochrome p450 2E1 and iron in ALD. Alcohol-mediated hepatocarcinogenesis is also discussed in the presence or absence of co-morbidities such as viral hepatitis C as well as therapeutic the role of innate immunity in ALD-HCV. Moreover, emphasis was placed on alcohol and drug interactions, as well as liver transplantation for end-stage ALD. Finally, the time came to eradicate alcohol-induced liver and intestinal damage by using betaine.
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Affiliation(s)
- Manuela G Neuman
- In Vitro Drug Safety and Biotechnology, Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
| | - Stephen Malnick
- Division of Gastroenterology, Kaplan Health Sciences Centre, Department of Medicine, Faculty of Medicine, Hebrew University, Rehovot, Israel
| | - Yaakov Maor
- Division of Gastroenterology, Kaplan Health Sciences Centre, Department of Medicine, Faculty of Medicine, Hebrew University, Rehovot, Israel
| | - Radu M Nanau
- In Vitro Drug Safety and Biotechnology, Toronto, Ontario, Canada
| | - Ehud Melzer
- Division of Gastroenterology, Kaplan Health Sciences Centre, Department of Medicine, Faculty of Medicine, Hebrew University, Rehovot, Israel
| | | | - Helmut K Seitz
- University of Heidelberg, Heidelberg, Germany; Department of Medicine, Gastroenterology and Hepatology, Centre for Alcohol Research, Salem Medical Centre, Heidelberg, Germany
| | - Sebastian Mueller
- University of Heidelberg, Heidelberg, Germany; Department of Medicine, Gastroenterology and Hepatology, Centre for Alcohol Research, Salem Medical Centre, Heidelberg, Germany
| | - Haim Mell
- Israel Antidrug and Alcohol Authority, Jerusalem, Israel
| | - Didier Samuel
- Liver Transplant Unit, Research Inserm-Paris XI Unit 785, Centre Hepatobiliaire, Hopital Paul Brousse, Villejuif, Paris, France
| | - Lawrence B Cohen
- Division of Gastroenterology, Sunnybrook Health Sciences Centre and Department of Internal Medicine, University of Toronto, Toronto, Canada
| | - Kusum K Kharbanda
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Internal Medicine, Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Natalia A Osna
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Internal Medicine, Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Murali Ganesan
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Internal Medicine, Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Kyle J Thompson
- Department of Surgery, Carolinas Medical Center, Charlotte, NC 28203, USA
| | - Iain H McKillop
- Department of Surgery, Carolinas Medical Center, Charlotte, NC 28203, USA
| | - Abraham Bautista
- Office of Extramural Activities, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, USA
| | - Ramon Bataller
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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19
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Sex difference in liver-related mortality and transplantation associated with dietary cholesterol in chronic hepatitis C virus infection. Br J Nutr 2015; 115:193-201. [PMID: 26541123 DOI: 10.1017/s0007114515004158] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Dietary cholesterol induces hepatic inflammation and fibrosis in animals. We aimed to determine whether dietary cholesterol affects liver-related mortality in hepatitis C virus (HCV)-infected patients. We performed a retrospective cohort study using extended follow-up data from the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis Trial. The study included HCV patients with advanced fibrosis and compensated cirrhosis. The analysis included 657 patients who completed two FFQ. We assessed whether cholesterol intake, measured in mg/4184 kJ (mg/1000 kcal) of energy intake, was associated with liver-related death or transplantation. In 4·7 (sd 1·6) years, the incidence of liver-related death (n 46) or transplantation (n 52) was 31·8/1000 person-years. The relationship between cholesterol intake and liver-related death or transplantation was significantly different between men and women (test for interaction, P value=0·01). Each higher quartile of cholesterol intake was associated with an increased risk for liver-related death or transplantation in women (adjusted hazard ratio (AHR) 1·83; 95 % CI 1·12, 2·99; P trend=0·02), but not in men (AHR 0·96; 95 % CI 0·76, 1·22; P trend=0·73). Compared with women whose cholesterol intake was within the recommended guidelines (300 mg/d with a 8368 kJ (2000 kcal) diet), women who consumed more cholesterol had significantly increased risk for liver-related death or transplantation (AHR 4·04; 95 % CI 1·42, 11·5). High dietary cholesterol was associated with an increased risk for liver-related death and transplantation in HCV-infected women with advanced fibrosis or compensated cirrhosis. Future studies should assess whether reducing cholesterol intake, among women who consume an excessive amount, can decrease HCV-related mortality.
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20
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Hiramine S, Sugiyama M, Furusyo N, Uto H, Ido A, Tsubouchi H, Watanabe H, Ueno Y, Korenaga M, Murata K, Masaki N, Hayashi J, Thomas DL, Mizokami M. A thymine-adenine dinucleotide repeat polymorphism near IL28B is associated with spontaneous clearance of hepatitis C virus. J Gastroenterol 2015; 50:1069-1077. [PMID: 25735432 PMCID: PMC4651429 DOI: 10.1007/s00535-015-1056-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2014] [Accepted: 02/11/2015] [Indexed: 02/04/2023]
Abstract
BACKGROUND Genome-wide association studies have revealed several single-nucleotide polymorphisms around interleukin 28B (IL28B) that are strongly associated with hepatitis C virus (HCV) clearance. However, their predictive value is not perfect, which suggests that other genetic factors may also be involved in HCV clearance. We previously reported a wide variation in the length of a thymine-adenine (TA) dinucleotide repeat in the promoter region of IL28B and that the transcriptional activity of the promoter increased gradually in a TA repeat length-dependent manner. METHODS We determined the length of the TA repeats of 1,060 Japanese and 201 African-American samples to investigate the relation to spontaneous HCV clearance. RESULTS The distribution of the TA repeats greatly differed between the two ethnicities. The variation ranged from 10 to 18 repeats, and the most frequent allele, 12, accounted for over 80% for Japanese. The African-American data showed a gently sloping distribution, and the allele with six repeats was detected only in the African-American sample. The TA repeats 11 or greater were correlated with spontaneous clearance. Multiple logistic regression analysis extracted the genotype of the TA repeats as an independent factor in both the Japanese [p = 0.0004, odds ratio (OR) = 13.02 95% confidence interval (CI) = 2.59-237.0] and African-American (p = 0.027, OR = 3.70 95% CI = 1.16-11.8) populations. CONCLUSIONS A long TA repeat in the promoter region of IL28B was associated with spontaneous HCV clearance. Although its efficacy may be limited in Japanese population because of its allele distribution, this novel genetic factor will be useful for predicting HCV clearance especially for the African Americans.
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Affiliation(s)
- Satoshi Hiramine
- Department of Hepatic Diseases, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Kohonodi, Ichikawa, 272-8516, Chiba, Japan
- General Internal Medicine Department, Kyushu University Hospital, Fukuoka, 812-8582, Japan
| | - Masaya Sugiyama
- Department of Hepatic Diseases, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Kohonodi, Ichikawa, 272-8516, Chiba, Japan
| | - Norihiro Furusyo
- General Internal Medicine Department, Kyushu University Hospital, Fukuoka, 812-8582, Japan
| | - Hirofumi Uto
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 890-8544, Japan
| | - Akio Ido
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 890-8544, Japan
| | - Hirohito Tsubouchi
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 890-8544, Japan
| | - Hisayoshi Watanabe
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, 990-9585, Japan
| | - Yoshiyuki Ueno
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, 990-9585, Japan
| | - Masaaki Korenaga
- Department of Hepatic Diseases, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Kohonodi, Ichikawa, 272-8516, Chiba, Japan
| | - Kazumoto Murata
- Department of Hepatic Diseases, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Kohonodi, Ichikawa, 272-8516, Chiba, Japan
| | - Naohiko Masaki
- Department of Hepatic Diseases, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Kohonodi, Ichikawa, 272-8516, Chiba, Japan
| | - Jun Hayashi
- General Internal Medicine Department, Kyushu University Hospital, Fukuoka, 812-8582, Japan
| | - David L Thomas
- Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA
| | - Masashi Mizokami
- Department of Hepatic Diseases, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Kohonodi, Ichikawa, 272-8516, Chiba, Japan.
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21
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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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22
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McGlynn KA, Petrick JL, London WT. Global epidemiology of hepatocellular carcinoma: an emphasis on demographic and regional variability. Clin Liver Dis 2015; 19:223-38. [PMID: 25921660 PMCID: PMC4712629 DOI: 10.1016/j.cld.2015.01.001] [Citation(s) in RCA: 644] [Impact Index Per Article: 64.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Liver cancer is the second leading cause of global cancer mortality. The major risk factors for hepatocellular carcinoma (HCC) are being addressed with success by prevention efforts. Vaccination against hepatitis B virus has reduced incidence of HCC in Taiwan and is partly responsible for lower rates in China. New infections with hepatitis C virus are low in developed countries because of prevention of posttransfusion infections and reduced exposure to HCV by drug users. Aflatoxin exposure has been reduced by better grain storage and dietary changes. Obesity, metabolic syndrome, and diabetes are increasing in developed and developing countries and will lead to more cases of HCC.
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Affiliation(s)
- Katherine A. McGlynn
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20854
| | - Jessica L. Petrick
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20854
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23
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Abstract
Chronic hepatitis C virus (HCV) infection is a major cause of cirrhosis and hepatocellular carcinoma worldwide and the leading indication for liver transplantation in the adult United States population. Although the incidence of chronic HCV infection is declining, the number of deaths is projected to rise over the next decade. Hence, the major reason for treating chronic HCV infection is to mitigate the morbidity and mortality associated with the infection but also to alleviate patient symptoms and to prevent person-to-person transmission. Successful eradication or virological cure is possible and a reduction in liver-related outcomes has been demonstrated in patients with advanced liver disease who achieve this desirable endpoint.–
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Affiliation(s)
- Marc G Ghany
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland
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24
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Dienstag JL, Delemos AS. Viral Hepatitis. MANDELL, DOUGLAS, AND BENNETT'S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES 2015:1439-1468.e7. [DOI: 10.1016/b978-1-4557-4801-3.00119-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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25
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Prieto Ortíz JE, Sánchez Pardo S, Rojas Díaz EL, Huertas Pacheco SJ. Hepatitis C crónica: aspectos clínicos, serológicos y de tratamiento en dos centros de atención en Bogotá, Colombia. ACTA ACUST UNITED AC 2014. [DOI: 10.22516/25007440.440] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Introducción: el virus de la hepatitis C afecta a cerca de 170 millones de personas en el mundo. La organización mundial de la salud (OMS) estima una prevalencia mundial del 2%. La respuesta global al tratamiento en la era de la terapia dual para genotipo 1 es del orden de 40%. En Colombia hay datos limitados que confirmen un comportamiento similar y que describan las características clínicas de los pacientes con esta infección. Metodología: se revisaron retrospectivamente las historias clínicas de pacientes con diagnóstico de hepatitis C crónica que asistieron a consulta externa del servicio de Hepatología en la Clínica Universitaria Colombia y de la consulta externa del servicio de Hepatología de uno de los autores durante el periodo comprendido entre el 1 de enero del 2010 y el 30 de mayo de 2013, se describen las características clínicas, serológicas y de respuesta al tratamiento. Resultados: se evaluaron las historias clínicas de 163 pacientes, 62% mujeres y 38% hombres, con una edad promedio de 58,2 años. El principal factor de riesgo para la adquisición de la hepatitis C fue historia de transfusiones antes de 1992 en 62% de los pacientes. La decisión de iniciar tratamiento se tomó en 77 pacientes (47,2%) y en 86 (52,8%) no se inició por diferentes razones dentro de las cuales la edad avanzada y cirrosis avanzada suman más de 50%; otras razones para no iniciar el tratamiento fueron: enfermedad mínima (4,7%), enfermedad mínima más edad avanzada (10,5%), curación espontánea (14%), poca probabilidad de respuesta (3,3%) y otras (14%). De 62 pacientes de los que se contaba con información acerca de tratamientos previos o tratados recientemente 30,6% presentaron respuesta viral sostenida (RVS), 29,0% fueron clasificados como reincidentes o relapser, 8,1% como respondedores parciales, 19,4% no tuvieron respuesta y 12,9% suspendieron el tratamiento por intolerancia. Conclusiones: el antecedente más frecuente para la adquisición del VHC en el grupo de pacientes estudiado fue la historia de transfusiones antes de 1992 asociada con cirugía ginecológica. Cerca de la mitad de los pacientes se diagnostican tardíamente. Se muestra una mayor tendencia al tratamiento de la hepatitis con tasas de RVS similares a las encontradas en otras series. Este estudio abre puertas a la realización de otros que permitan definir de forma más amplia la prevalencia, factores de riesgo y variables de respuesta al tratamiento de esta entidad en nuestro país.
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Ancient pathogen genomics: insights into timing and adaptation. J Hum Evol 2014; 79:137-49. [PMID: 25532802 DOI: 10.1016/j.jhevol.2014.11.002] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2014] [Revised: 09/08/2014] [Accepted: 11/05/2014] [Indexed: 12/15/2022]
Abstract
Disease is a major cause of natural selection affecting human evolution, whether through a sudden pandemic or persistent morbidity and mortality. Recent contributions in the field of ancient pathogen genomics have advanced our understanding of the antiquity and nature of human-pathogen interactions through time. Technical advancements have facilitated the recovery, enrichment, and high-throughput sequencing of pathogen and parasite DNA from archived and archaeological remains. These time-stamped genomes are crucial for calibrating molecular clocks to infer the timing of evolutionary events, while providing finer-grain resolution to phylogenetic reconstructions and complex biogeographical patterns. Additionally, genome scale data allow better identification of substitutions linked to adaptations of the pathogen to their human hosts. As methodology continues to improve, ancient genomes of humans and their diverse microbiomes from a range of eras and archaeological contexts will enable population-level ancient analyses in the near future and a better understanding of their co-evolutionary history.
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Atas M, Karatepe Hashas AS, Demircan S, Sarıguzel FM, Baskan B, Yuvacı I, Pangal E, Celik I, Zararsiz G. The Investigation of HCV RNA in Tear Fluid and Aqueous Humor in Patients with Anti-HCV Antibody Positive Who Underwent Cataract Surgery. Ocul Immunol Inflamm 2014; 24:297-301. [PMID: 25495483 DOI: 10.3109/09273948.2014.985386] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
PURPOSE To obtain aqueous humor and tear fluid samples during cataract surgery of the hepatitis C virus (HCV)-antibody-positive patients in order to analyze them for HCV RNA and compare these measurements with serum HCV RNA levels. METHODS Twenty-nine anti-HCV-positive patients were included this study. HCV RNA viral load levels were determined by commercial real-time polymerase chain reaction system. Antibodies to HCV were screened with the enzyme-linked immunosorbent assay (ELISA) using anti-HCV test kit. RESULTS Log10 HCV RNA levels were found to be 6.00 ± 1.06 IU/mL in serum, 2.76 ± 0.36 IU/mL in the aqueous humor, and 1.91 ± 0.93 IU/mL in tear fluid. No correlation was detected between samples for HCV RNA positivity (p = .390, κ = .102). We have observed that, viral RNA was detected in the aqueous humor, while not in serum in one case, whereas viral RNA was detected in tear fluid but not in serum in another case. CONCLUSIONS Although viral load detected in aqueous humor and tear fluid samples was considerably lower compared to the serum samples, it can still be important in terms of infectivity.
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Affiliation(s)
- Mustafa Atas
- a Kayseri Training and Research Hospital, Ophthalmology , Kayseri , Turkey
| | | | - Süleyman Demircan
- a Kayseri Training and Research Hospital, Ophthalmology , Kayseri , Turkey
| | - Fatma Mutlu Sarıguzel
- b Kayseri Training and Research Hospital, Department of Clinical Microbiology and Infectious Diseases , Kayseri , Turkey , and
| | - Burhan Baskan
- a Kayseri Training and Research Hospital, Ophthalmology , Kayseri , Turkey
| | - Isa Yuvacı
- a Kayseri Training and Research Hospital, Ophthalmology , Kayseri , Turkey
| | - Emine Pangal
- a Kayseri Training and Research Hospital, Ophthalmology , Kayseri , Turkey
| | - Ilhami Celik
- b Kayseri Training and Research Hospital, Department of Clinical Microbiology and Infectious Diseases , Kayseri , Turkey , and
| | - Gokmen Zararsiz
- c Erciyes University Faculty of Medicine, Biostatistics , Kayseri , Turkey
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Backus LI, Belperio PS, Loomis TP, Mole LA. Impact of race/ethnicity and gender on HCV screening and prevalence among U.S. veterans in Department of Veterans Affairs Care. Am J Public Health 2014; 104 Suppl 4:S555-61. [PMID: 25100421 DOI: 10.2105/ajph.2014.302090] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
OBJECTIVES We assessed HCV screening and prevalence among veterans and estimated the potential impact of complete birth cohort screening, accounting for the disparate HCV disease burden by race/ethnicity and gender. METHODS We used the Department of Veterans Affairs (VA) Corporate Data Warehouse to identify birth dates, gender, race/ethnicity, and laboratory tests for veterans with at least 1 VA outpatient visit in 2012. We calculated HCV screening rates, prevalence, and HCV infection incident diagnosis. RESULTS Among 5,499,743 veterans, 54.7% had HCV screening through the VA. In more than 2.9 million veterans screened, HCV prevalence was 6.1% overall and highest among Blacks (11.8%), particularly Black men born in 1945 to 1965 (17.7%). HCV infection incident diagnosis in 2012 was 5.9% for men and 2.3% for women. An estimated additional 48,928 male veterans, including 12,291 Black men, and 1484 female veterans would potentially be identified as HCV infected with full birth cohort screening. CONCLUSIONS HCV prevalence was markedly elevated among veterans born in 1945 to 1965, with substantial variation by race/ethnicity and gender. Full adoption of birth cohort screening may reveal substantial numbers of veterans with previously unknown HCV infection.
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Affiliation(s)
- Lisa I Backus
- Lisa I. Backus, Pamela S. Belperio, Timothy P. Loomis, and Larry A. Mole are with the Department of Veterans Affairs, Office of Public Health/Population Health, Washington, DC. Lisa Backus is also with the Department of Medicine, VA Palo Alto Health Care System, Palo Alto, CA. Pamela S. Belperio is also with the Department of Pharmacy, VA Greater Los Angeles Health Care System, Los Angeles, CA
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Seaberg EC, Witt MD, Jacobson LP, Detels R, Rinaldo CR, Young S, Phair JP, Thio CL. Differences in hepatitis C virus prevalence and clearance by mode of acquisition among men who have sex with men. J Viral Hepat 2014; 21:696-705. [PMID: 25280229 PMCID: PMC4187219 DOI: 10.1111/jvh.12198] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2013] [Accepted: 09/21/2013] [Indexed: 01/29/2023]
Abstract
We examined the characteristics associated with hepatitis C virus (HCV) antibody (anti-HCV) prevalence and HCV clearance between injection drug using (IDU) and non-IDU men who have sex with men (MSM). Stored serum and plasma samples were tested for anti-HCV and HCV RNA to determine the HCV status of 6925 MSM at enrolment into the Multicentre AIDS Cohort Study (MACS). Prevalence and clearance ratios were calculated to determine the characteristics associated with HCV prevalence and clearance. Multivariable analyses were performed using Poisson regression methods with robust variance estimation. Anti-HCV prevalence was significantly higher among IDU than among non-IDU MSM (42.9% vs 4.0%), while clearance was significantly lower among IDU MSM (11.5% vs 34.5% among non-IDU MSM). HIV infection, Black race, and older age were independently associated with higher prevalence in both groups, while smoking, transfusion history, and syphilis were significantly associated with prevalence only among non-IDU MSM. The rs12979860-C/C genotype was the only characteristic independently associated with HCV clearance in both groups, but the effects of both rs12979860-C/C genotype [clearance ratio (CR) = 4.16 IDUs vs 1.71 non-IDUs; P = 0.03] and HBsAg positivity (CR = 5.06 IDUs vs 1.62 non-IDUs; P = 0.03) were significantly larger among IDU MSM. HIV infection was independently associated with lower HCV clearance only among non-IDU MSM (CR = 0.59, 95% CI = 0.40-0.87). IDU MSM have higher anti-HCV prevalence and lower HCV clearance than non-IDU MSM. Differences in the factors associated with HCV clearance suggest that the mechanisms driving the response to HCV may differ according to the mode of acquisition.
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Affiliation(s)
- Eric C Seaberg
- Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, 21205 USA
| | - Mallory D Witt
- David Geffen School of Medicine, University of California, Los Angeles, CA and Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, California, 90509 USA
| | - Lisa P Jacobson
- Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, 21205 USA
| | - Roger Detels
- Department of Epidemiology, UCLA School of Public Health, Los Angeles, California, 90095 USA
| | - Charles R Rinaldo
- Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, 15261 USA
| | - Steve Young
- TriCore Reference Laboratory, Albuquerque, New Mexico, 87131 USA
| | - John P Phair
- Howard Brown Health Center and Department of Medicine, Northwestern University, Chicago, Illinois, 60611 USA
| | - Chloe L Thio
- Department of Medicine, Johns Hopkins University, Baltimore, Maryland, 21205 USA
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Colagreco JP, Bailey DE, Fitzpatrick JJ, Musil CM, Afdhal NH, Lai M. Watchful waiting: role of disease progression on uncertainty and depressive symptoms in patients with chronic hepatitis C. J Viral Hepat 2014; 21:727-33. [PMID: 25280230 PMCID: PMC4185928 DOI: 10.1111/jvh.12207] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2013] [Accepted: 09/11/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS New therapies for HCV are rapidly emerging and providers are advising select patients to defer treatment and elect 'watchful waiting'. During the watchful waiting period, patients have been shown to have high rates of illness uncertainty and depression. We sought to answer the question of whether reassuring histological data (showing minimal fibrosis or no fibrosis progression over time) is associated with less illness uncertainty and depressive symptoms. METHODS This was a single-centre outpatient prospective cohort study to determine whether stage of fibrosis, fibrosis progression and reasons for treatment deferral were related to illness uncertainty and depressive symptoms in patients following watchful waiting. RESULTS Illness uncertainty was significantly related to depressive symptoms (r = 0.49, P < 0.01). More than half of the participants (54%) had moderate levels of uncertainty. About 40% of the participants were at risk for clinical depression (21.7% at mild to moderate risk and 18.5% at high risk). Treatment naïve subjects had lower mean scores on both the CES-D (depressive symptoms measure) and the MUIS-A (illness uncertainty measure) total score, MUIS-A Ambiguity subscale and MUIS-A Inconsistency subscale than subjects who failed treatment or were interferon intolerant or ineligible. Surprisingly, liver fibrosis stage and progression were not significantly associated with overall illness uncertainty or depressive symptoms. CONCLUSION Patients with chronic hepatitis C on watchful waiting are at high risk for significant illness uncertainty and depressive symptoms. Reassuring histological data does not seem to correlate with less uncertainty or depressive symptoms.
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Affiliation(s)
| | | | | | - Carol M. Musil
- Frances Payne Bolton School of Nursing, Case Western Reserve University
| | | | - Michelle Lai
- Harvard University, Beth Israel Deaconess Medical Center
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Zhang K, Wang L, Sun Y, Zhang R, Lin G, Xie J, Li J. Improving the safety of blood transfusion by using a combination of two screening assays for hepatitis C virus. Transfus Med 2014; 24:297-304. [PMID: 25262976 DOI: 10.1111/tme.12152] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2014] [Revised: 07/22/2014] [Accepted: 08/19/2014] [Indexed: 12/30/2022]
Abstract
BACKGROUND AND OBJECTIVES To illustrate that the combination of a single nucleic acid amplification test (NAT) with a single immunoassay for hepatitis C virus (HCV) detection, as proposed internationally, may lead to the omission of anti-HCV reactive sera with non-reactive NAT results. MATERIALS AND METHODS In total, 822 of 519, 299 serum samples from 11 blood centres in China were retested for anti-HCV by using 10 screening assays to detect HCV antibodies. A recombinant immunoblot assay (RIBA HCV 3·0; Ortho-Clinical Diagnostics) was performed to define confirmed HCV infection status. Samples with positive or indeterminate RIBA-HCV results were tested by quantitative tests for HCV RNA (Roche Diagnostics). RESULTS We found that 47 of the 822 (5·72%) serum samples were RIBA-positive without detectable HCV RNA. For these samples, the 10 anti-HCV immunoassays gave discordant and unsatisfactory results (detection rate ranging from 10·64 to 34·04%; ratio per 100 000 donations ranging from 5·97 to 8·09). Compared with a single anti-HCV screening assay, the two-assay combination increased the detection of these samples. The five best combinations [Sorin and Lizhu enzyme immunoassays (EIAs), Ortho and Lizhu EIAs, Sorin and Wantai EIAs, Sorin EIA and Roche CIA and Ortho and Wantai EIAs] increased the detection rate from 46·81 to 55·57%, thus reducing the ratio per 100 000 donations of HCV-seropositive samples. CONCLUSION The combination of two anti-HCV screening immunoassays in parallel with an HCV NAT is a better strategy for HCV detection in blood centres to improve the safety of blood transfusion.
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Affiliation(s)
- K Zhang
- National Center for Clinical Laboratories, Beijing Hospital, Beijing, People's Republic of China
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Wysocki J, Newby C, Balart L, Shores N. HCV Triple Therapy is Equally effective in African-Americans and Non-African-Americans. J Racial Ethn Health Disparities 2014. [DOI: 10.1007/s40615-014-0039-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Zavaglia C, Silini E, Mangia A, Airoldi A, Piazzolla V, Vangeli M, Stigliano R, Foschi A, Mazzarelli C, Tinelli C. Prognostic factors of hepatic decompensation and hepatocellular carcinoma in patients with transfusion-acquired HCV infection. Liver Int 2014; 34:e308-16. [PMID: 24529078 DOI: 10.1111/liv.12502] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2013] [Accepted: 02/08/2014] [Indexed: 12/20/2022]
Abstract
AIMS Aim of this study was to assess if host (immunogenetic traits, age, sex), exogenous (alcohol) or viral factors (viral type, past HBV infection) might affect the progression of chronic hepatitis C to liver decompensation or the development of HCC in a cohort of patients exposed to a single blood transfusion prior to the introduction of anti-HCV screening. METHODS Two hundred and forty-eight patients with a history of a single exposure to blood or blood products prior to 1990 were retrospectively considered. Patients were devoid of other risk factors of liver disease or immunosuppression and naïve to antiviral therapies. Eight baseline variables were assessed: age at transfusion, sex, HBV core antibody, immunogenetic profile (DRB1*11, DRB1*1104, DRB1*07), HCV genotype and alcohol consumption. RESULTS The follow-up was 22 (SD: 11) years. Sixty-eight patients (27%) progressed to hepatic decompensation over a median period of 22.5 years (IQR: 14-30) and 41 patients (16%) developed HCC over a median period of 31 years (IQR: 24-38). The cumulative incidence of liver failure was 0.4% (95% CI: 0.1-3.1), 4.9% (95% CI: 2.6-9.3) and 16.2% (95% CI: 10.4-24.7) at 10, 20 and 30 years after blood transfusion respectively. By univariate analysis, only age at transfusion was correlated with the risk of decompensation. Stratifying the age of transfusion by tertiles, the incidence of hepatic decompensation was 0.7% per year in patients transfused at ≤24 years of age as compared to 1.2% and 1.9% per year in those transfused at 25-35 and >36 years of age respectively (HR: 5.5, 95% CI: 2.78-10.7, P<0.001). The risk of HCC development was correlated by univariate analysis with age at transfusion (as continuous variable, HR: 1.12, 95% CI: 1.08-1.16 per year of age, P<0.001, >36 compared to ≤24 years, HR: 10.3, 95% CI: 3.9-26.9, P<0.001) and male sex (HR: 4.2, 95% CI: 1.7-10, P=0.001). Multivariate analysis confirmed age at transfusion and male sex as independent predictors of HCC development [HR: 1.12 per year (95% CI: 1.08-1.16), P<0.001 and HR: 5.4 (95% CI: 2.2-13.2), P<0.001 respectively]. CONCLUSIONS In patients with transfusion-acquired HCV infection, age at transfusion affects the risk for hepatic decompensation. Age at transfusion and male sex are independent risk factors for HCC development.
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Affiliation(s)
- Claudio Zavaglia
- Struttura Complessa di Gastroenterologia ed Epatologia 'Crespi', Ospedale Niguarda, piazza Ospedale Maggiore 3, 20162, Milano, Italy
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Forde KA, Tanapanpanit O, Reddy KR. Hepatitis B and C in African Americans: current status and continued challenges. Clin Gastroenterol Hepatol 2014; 12:738-48. [PMID: 23811241 PMCID: PMC3947744 DOI: 10.1016/j.cgh.2013.06.006] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2013] [Revised: 06/15/2013] [Accepted: 06/17/2013] [Indexed: 02/07/2023]
Abstract
Viral hepatitis remains a public health concern in the United States, resulting in excess morbidity and mortality for the individual and representing a burden to societies as evidenced by billions of dollars in health care expenditures. As with many chronic diseases, race and ethnicity influence various aspects of disease pathogenesis, including mechanisms of persistence, disease progression, disease sequelae, and response to therapy. For hepatitis B and C infections, African Americans disproportionately bear a large burden of disease in the United States. The role and importance of African American race, however, have been less well-characterized in the literature among the population of viral hepatitis-infected individuals. The differences in epidemiology, manifestations of liver disease, response to therapy, and differential trends in liver transplantation in African Americans compared with other racial and ethnic groups deserve special attention. This review will address the current status of hepatitis B and C infection in African Americans in the United States and identify some of the remaining challenges in diagnosis, characterization of natural history, and treatment. For the purposes of this review, the terms African American and black will be used interchangeably throughout the text.
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Affiliation(s)
- Kimberly A. Forde
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.,Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Orapin Tanapanpanit
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - K. Rajender Reddy
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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Yu L, Morishima C, Ioannou GN. Dietary cholesterol intake is associated with progression of liver disease in patients with chronic hepatitis C: analysis of the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis trial. Clin Gastroenterol Hepatol 2013; 11:1661-6.e1-3. [PMID: 23707779 DOI: 10.1016/j.cgh.2013.05.018] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2012] [Revised: 04/18/2013] [Accepted: 05/01/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Little is known about whether dietary cholesterol affects disease progression in patients with chronic hepatitis C virus infection. METHODS We analyzed data from the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis trial, which included patients with advanced fibrosis and compensated cirrhosis. Cholesterol intake was determined for 608 participants on the basis of responses to food frequency questionnaires, administered at baseline and 1.8 years later. We investigated whether cholesterol intake was associated with clinical progression (death, variceal bleeding, encephalopathy, ascites, peritonitis, Child-Turcotte-Pugh score ≥ 7, or hepatocellular carcinoma) or histologic progression of disease (an increase in Ishak fibrosis score of 2 or more points in a second liver biopsy compared with the first). RESULTS After adjustments for age, sex, race, presence of cirrhosis, body mass index, treatment with peginterferon, lifetime alcohol consumption, smoking, health status, and coffee and macronutrient intake, each higher quartile of cholesterol intake was associated with a 46% increase in the risk of clinical or histologic progression (adjusted hazard ratio [AHR], 1.46; 95% confidence interval [CI], 1.13-1.87; P for the trend = .004). Compared with patients in the lowest quartile of cholesterol intake (32-152 mg/day), those in the 3rd (224-310 mg/day; AHR, 2.83; 95% CI, 1.45-5.51) and 4th quartiles (>310 mg/day; AHR, 2.74; 95% CI, 1.22-6.16) had significantly increased risk of disease progression. CONCLUSIONS On the basis of analysis of data from the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis trial, higher dietary cholesterol intake is associated with higher risk of disease progression in HCV-infected patients with advanced fibrosis or compensated cirrhosis.
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Affiliation(s)
- Lei Yu
- Division of Gastroenterology, University of Washington, Seattle, Washington.
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Gray RR, Tanaka Y, Takebe Y, Magiorkinis G, Buskell Z, Seeff L, Alter HJ, Pybus OG. Evolutionary analysis of hepatitis C virus gene sequences from 1953. Philos Trans R Soc Lond B Biol Sci 2013; 368:20130168. [PMID: 23938759 PMCID: PMC3758194 DOI: 10.1098/rstb.2013.0168] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Reconstructing the transmission history of infectious diseases in the absence of medical or epidemiological records often relies on the evolutionary analysis of pathogen genetic sequences. The precision of evolutionary estimates of epidemic history can be increased by the inclusion of sequences derived from 'archived' samples that are genetically distinct from contemporary strains. Historical sequences are especially valuable for viral pathogens that circulated for many years before being formally identified, including HIV and the hepatitis C virus (HCV). However, surprisingly few HCV isolates sampled before discovery of the virus in 1989 are currently available. Here, we report and analyse two HCV subgenomic sequences obtained from infected individuals in 1953, which represent the oldest genetic evidence of HCV infection. The pairwise genetic diversity between the two sequences indicates a substantial period of HCV transmission prior to the 1950s, and their inclusion in evolutionary analyses provides new estimates of the common ancestor of HCV in the USA. To explore and validate the evolutionary information provided by these sequences, we used a new phylogenetic molecular clock method to estimate the date of sampling of the archived strains, plus the dates of four more contemporary reference genomes. Despite the short fragments available, we conclude that the archived sequences are consistent with a proposed sampling date of 1953, although statistical uncertainty is large. Our cross-validation analyses suggest that the bias and low statistical power observed here likely arise from a combination of high evolutionary rate heterogeneity and an unstructured, star-like phylogeny. We expect that attempts to date other historical viruses under similar circumstances will meet similar problems.
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Affiliation(s)
| | - Yasuhito Tanaka
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Kawasumi, Mizuho, Nagoya, Japan
| | - Yutaka Takebe
- AIDS Research Center, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
| | | | - Zelma Buskell
- Veterans Affairs Medical Center, Washington, DC, USA
| | | | - Harvey J. Alter
- Department of Transfusion Medicine, National Institutes of Health, Bethesda, MD, USA
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Reasons for Nonattendance across the Hepatitis C Disease Course. ISRN NURSING 2013; 2013:579529. [PMID: 24109517 PMCID: PMC3786544 DOI: 10.1155/2013/579529] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/27/2013] [Accepted: 08/02/2013] [Indexed: 02/06/2023]
Abstract
This descriptive qualitative study examined the patient, provider, and institutional factors contributing to nonattendance for hepatitis C (HCV) care throughout the disease course. Eighty-four patients and health and social care providers were interviewed. Thematic analysis of the data yielded 6 interrelated nonattendance themes: self-protection, determining the benefits, competing priorities, knowledge gaps, access to services, and restrictive policies. Factors within the themes varied with the disease course, type of provider/service, and patient context. Nonattendance could span months to years and most frequently began at diagnosis where providers either advised that followup was not necessary or did not recommend any followup. The way services were organized (low barrier access) and delivered (nonjudgmental approach) and higher HCV knowledge levels of patients and providers encouraged attendance. This is the first study to explore the reasons for nonattendance for HCV care throughout the disease course and validate them from multiple perspectives. There are missed opportunities for providers to encourage attendance throughout the disease course beginning at diagnosis. Interventions required include development of integrated health and social service delivery models; mechanisms to improve knowledge dissemination of the disease, its management, and treatment; and implementation of standardized followup protocols for liver disease monitoring in primary care.
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Koretz RL. Interferon for hepatitis C: where it has been and where it is going. Immunotherapy 2013; 5:673-5. [PMID: 23829615 DOI: 10.2217/imt.13.55] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
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Sarkar M, Bacchetti P, Tien P, Mileti E, French AL, Edlin BR, Keller M, Seaberg E, Nowicki MJ, Young M, Peter MG. Racial/ethnic differences in spontaneous HCV clearance in HIV infected and uninfected women. Dig Dis Sci 2013; 58. [PMID: 23179159 PMCID: PMC3663918 DOI: 10.1007/s10620-012-2486-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND/AIMS Among individuals without human immunodeficiency virus (HIV), African Americans have lower spontaneous clearance of hepatitis C virus (HCV) than Caucasians, and women have higher clearance than men. Few studies report racial/ethnic differences in acute HCV in HIV infected, or Hispanic women. We examined racial/ethnic differences in spontaneous HCV clearance in a population of HCV mono- and co-infected women. METHODS We conducted a cross sectional study of HCV seropositive women (897 HIV infected and 168 HIV uninfected) followed in the US multicenter, NIH-funded Women's Interagency HIV Study (WIHS), to determine the association of race/ethnicity with spontaneous HCV clearance, as defined by undetectable HCV RNA at study entry. RESULTS Among HIV and HCV seropositive women, 18.7 % were HCV RNA negative, 60.9 % were African American, 19.3 % Hispanic and 17.7 % Caucasian. HIV infected African American women were less likely to spontaneously clear HCV than Hispanic (OR 0.59, 95 % CI 0.38-0.93, p = 0.022) or Caucasian women (OR 0.57, 95 % CI 0.36-0.93, p = 0.023). Among HIV uninfected women, African Americans had less HCV clearance than Hispanics (OR 0.18, 95 % CI 0.07-0.48, p = 0.001) or Caucasians (OR 0.26, 95 % CI 0.09-0.79, p = 0.017). There were no significant differences in HCV clearance between Hispanics and Caucasians, among either HIV infected (OR 0.97, 95 % CI 0.57-1.66, p = 0.91) or uninfected (OR 1.45, 95 % CI 0.56-3.8, p = 0.45) women. CONCLUSIONS African Americans were less likely to spontaneously clear HCV than Hispanics or Caucasians, regardless of HIV status. No significant differences in spontaneous HCV clearance were observed between Caucasian and Hispanic women. Future studies incorporating IL28B genotype may further explain these observed racial/ethnic differences in spontaneous HCV clearance.
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Affiliation(s)
- Monika Sarkar
- Department of Medicine, Division of Gastroenterology and Hepatology, University of California, San Francisco, 513 Parnassus Avenue, Room S-357, San Francisco, CA 94143-0358, USA
| | - Peter Bacchetti
- Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA
| | - Phyllis Tien
- Department of Medicine, Division of Infectious Diseases, University of California, San Francisco, San Francisco, CA, USA
| | - Elizabeth Mileti
- Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA
| | - Audrey L. French
- Department of Medicine, CORE Center/Stroger Hospital of Cook County, Chicago, IL, USA
| | - Brian R. Edlin
- Department of Medicine, Division of Infectious Diseases, SUNY Downstate Medical Center, Brooklyn, NY, USA
| | - Marla Keller
- Department of Medicine, Division of Infectious Diseases, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Eric Seaberg
- Department of Epidemiology and Biostatistics, Johns Hopkins University, Baltimore, MD, USA
| | - Marek J. Nowicki
- Department of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Mary Young
- Department of Medicine, Division of Infectious Diseases, Georgetown University, Washington, DC, USA
| | - Marion G. Peter
- Department of Medicine, Division of Gastroenterology and Hepatology, University of California, San Francisco, 513 Parnassus Avenue, Room S-357, San Francisco, CA 94143-0358, USA
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Magiorkinis G, Sypsa V, Magiorkinis E, Paraskevis D, Katsoulidou A, Belshaw R, Fraser C, Pybus OG, Hatzakis A. Integrating phylodynamics and epidemiology to estimate transmission diversity in viral epidemics. PLoS Comput Biol 2013; 9:e1002876. [PMID: 23382662 PMCID: PMC3561042 DOI: 10.1371/journal.pcbi.1002876] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2012] [Accepted: 11/15/2012] [Indexed: 12/13/2022] Open
Abstract
The epidemiology of chronic viral infections, such as those caused by Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV), is affected by the risk group structure of the infected population. Risk groups are defined by each of their members having acquired infection through a specific behavior. However, risk group definitions say little about the transmission potential of each infected individual. Variation in the number of secondary infections is extremely difficult to estimate for HCV and HIV but crucial in the design of efficient control interventions. Here we describe a novel method that combines epidemiological and population genetic approaches to estimate the variation in transmissibility of rapidly-evolving viral epidemics. We evaluate this method using a nationwide HCV epidemic and for the first time co-estimate viral generation times and superspreading events from a combination of molecular and epidemiological data. We anticipate that this integrated approach will form the basis of powerful tools for describing the transmission dynamics of chronic viral diseases, and for evaluating control strategies directed against them. To design strategies that efficiently mitigate an epidemic requires estimates of how many people each carrier is likely to infect, what is the variation of this number among infections, and what is the time needed for these transmissions to take place. The disciplines of epidemiology and population genetics independently provide partial answers to these questions by analysing surveillance data and molecular sequences, respectively. Here we propose a novel integration of the two fields that can reveal the underlying transmission dynamics of rapidly-evolving viruses such as HIV or HCV. We explore a well-described nationwide HCV epidemic and show that our method provides new insights into the nature and variation of HCV transmission among infected individuals. We suggest that this approach could form the basis of new tools that can help in the design of effective public health interventions targeting the spread of viral pathogens.
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Affiliation(s)
- Gkikas Magiorkinis
- Department of Hygiene, Epidemiology and Medical Statistics, Medical School, University of Athens, Athens, Greece.
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Koretz RL, Pleguezuelo M, Arvaniti V, Barrera Baena P, Ciria R, Gurusamy KS, Davidson BR, Burroughs AK. Interferon for interferon nonresponding and relapsing patients with chronic hepatitis C. Cochrane Database Syst Rev 2013; 2013:CD003617. [PMID: 23440791 PMCID: PMC6599819 DOI: 10.1002/14651858.cd003617.pub2] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND The widely-accepted treatment outcome for chronic hepatitis C is the sustained viral response (that is, no measurable viral RNA in blood six months after treatment). However, this surrogate outcome (as well as the previously employed biochemical and histologic ones) has never been validated. This situation exists because there are very few randomized clinical trials that have used clinical events (mortality or manifestations of decompensated cirrhosis) as outcomes, because those clinical events only occur after many years of infection. Patients in whom initial therapy fails to produce sustained viral responses do become potential candidates for retreatment; some of these individuals are not candidates for ribavirin or protease inhibitors and consideration could be given to retreatment with interferon alone. OBJECTIVES To assess the benefits and harms of interferon monotherapy retreatment in chronic hepatitis C patients and to validate the currently employed surrogate outcomes in this group of patients. SEARCH METHODS We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until 16 August 2012. SELECTION CRITERIA Randomized trials comparing interferon versus placebo or no treatment in chronic hepatitis C nonresponders and relapsers to previous interferon. DATA COLLECTION AND ANALYSIS The primary outcomes were mortality (all-cause and hepatic), quality of life, and adverse events. Secondary outcomes were liver-related morbidity, sustained viral responses, biochemical responses, histologic improvements, and costs. We used both fixed-effect and random-effects model meta-analyses, reporting only the former if no difference existed. MAIN RESULTS Seven trials were identified. Two of them were at low risk of bias (the HALT-C and EPIC3 trials) and included 1676 patients. Both of these trials addressed the role of long-term low-dose pegylated interferon therapy in patients with severe fibrosis (demonstrated on liver biopsy) and were designed to assess the clinical outcomes. The remaining five trials included 300 patients and were at high risk of bias. Based on all trials reporting the outcomes, no significant difference was observed in either all-cause mortality (78/843 (9.3%) versus 62/867 (7.2%); risk ratio (RR) 1.30, 95% confidence interval (CI) 0.95 to 1.79; 3 trials) or hepatic mortality (41/532 (7.7%) versus 40/552 (7.2%); RR 1.07, 95% CI 0.70 to 1.63; 2 trials); however, when only the two trials at low risk of bias were combined, all-cause mortality was significantly higher in the recipients of the pegylated interferon (78/828 (9.4%) versus 57/848 (6.7%); RR 1.41, 95% CI 1.02 to 1.96) although trial sequential analysis could not exclude the possibility of random error. There was less variceal bleeding in the recipients of the interferon (4/843 (0.5%) versus 18/867 (2.1%); RR 0.24, 95% CI 0.09 to 0.67; 3 trials), although again trial sequential analysis could not exclude the presence of a type I error and the effect could not be confirmed in a random-effects model meta-analysis. No significant differences were seen with regard to the development of ascites, encephalopathy, hepatocellular carcinoma, or the need for liver transplantation. One trial reported quality of life data; the pain score was significantly worse in the recipients of the pegylated interferon. Adverse effects tended to be more common in the interferon recipients; the ones that were significantly more common included hematologic complications, infections, flu-like symptoms, and rash. The recipients of interferon had significantly more sustained viral responses (20/557 (3.6%) versus 1/579 (0.2%); RR 15.38, 95% CI 2.93 to 80.71; 4 trials) and a type I error was excluded by trial sequential analysis. The METAVIR activity score also improved (36/55 (65%) versus 20/46 (43.5%); RR 1.49, 95% CI 1.02 to 2.18; 2 trials). No significant differences were seen with regard to histologic fibrosis assessments. AUTHORS' CONCLUSIONS The clinical data were limited to patients with histologic evidence of severe fibrosis who were retreated with pegylated interferon. In this scenario, retreatment with interferon did not appear to provide significant clinical benefit and, when only the trials at low risk of bias were considered, retreatment for several years may even have increased all-cause mortality. Such treatment also produced adverse events. On the other hand, the treatment did result in improvement in some surrogate outcomes, namely sustained viral responses and histologic evidence of inflammation. Interferon monotherapy retreatment cannot be recommended for these patients. No clinical data are available for patients with less severe fibrosis. The sustained viral response cannot be used as a surrogate marker for hepatitis C treatment in this clinical setting with low sustained viral response rates and needs to be validated in others in which higher sustained viral response rates are reported.
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Reggiardo MV, Fay F, Tanno M, García-Camacho G, Bottaso O, Ferretti S, Godoy A, Guerrita C, Paez M, Tanno F, Ruffinengo O, Benetti S, García Borrás SE, Rossi MC, Vorobioff J, Bessone F, Tanno H. Natural history of hepatitis C virus infection in a cohort of asymptomatic post-transfused subjects. Ann Hepatol 2012; 11:658-666. [PMID: 22947526 DOI: 10.1016/s1665-2681(19)31439-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/21/2025]
Abstract
UNLABELLED BACKGROUND & AIMS. Studies about the natural history of hepatitis C virus (HCV) infection report variable progression to cirrhosis depending on study design. Retrospective cross-sectional liver clinic studies overestimate the rate of fibrosis progression due to inclusion of patients with more severe disease leaving mild and asymptomatic patients underrepresented. We evaluated fibrosis progression in a group of "healthy" asymptomatic subjects, attending to a voluntary campaign for the detection of HCV infection. MATERIAL AND METHODS A detection campaign was launched on subjects transfused before 1993. Of 1699 volunteers, 61(3.6%) had HCV infection. A liver biopsy was performed in 40 (65%). Assessed risk factors for liver fibrosis were: sex, body mass index, alcohol consumption (> 20 g/d - > 40g/d ), genotype, HLA-DRB1 alleles, present age, age at infection and duration of infection. RESULTS 25 (62.5%) were women with a median age of 52.5 years. The median duration of infection was 21.5 years with a median age at infection of 27 years. As regards fibrosis, 25 (62.5%) had a Low Stage (F0-F1), 8 patients, 20%, had severe fibrosis, one patient (2.5%) had cirrhosis. Alcohol consumption was the only risk factor associated with fibrosis progression. CONCLUSIONS The low progression to cirrhosis may be explained by the clinical characteristics of our population: asymptomatic middle-aged "healthy" subjects infected at young age. The progression to severe fibrosis was noticeable; hence a longer follow-up might demonstrate changes in this outcome. Significant alcohol consumption clearly worsens the natural history of HCV infection; this is no so evident for occasional or mild alcohol consumers.
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Affiliation(s)
- María Virginia Reggiardo
- Gastroenterology and Hepatology Department, Hospital Provincial del Centenario, School of Medicine, University of Rosario, Argentina.
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Feld JJ. Treatment indication and response to standard of care with peginterferon and ribavirin in acute and chronic HCV infection. Best Pract Res Clin Gastroenterol 2012. [PMID: 23199502 DOI: 10.1016/j.bpg.2012.09.013] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Great strides have been made in the treatment of hepatitis C virus (HCV) infection in the past decade. Although there is much focus on the development of new direct-acting antivirals (DAA), interferon and ribavirin remain the backbone of therapy for both acute and chronic HCV infections. While DAA therapy will likely eventually largely replace interferon, in much of the world and for genotype non-1 patients, peginterferon and ribavirin remain first-line therapy. Interferon-based therapy is highly effective in acute HCV with high response rates with short courses of therapy. Unfortunately once infection progresses to chronicity, treatment success rates drop off considerably. The indications, pre-treatment evaluation and efficacy of peginterferon and ribavirin therapy in the treatment of acute and chronic HCV infection are discussed with strategies to improve outcomes and manage adverse events.
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Affiliation(s)
- Jordan J Feld
- Toronto Western Hospital Liver Centre, Sandra Rotman Centre for Global Health, University of Toronto, Toronto, Canada.
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Cusick MF, Libbey JE, Fujinami RS, Eckels DD. In vitro antigen-specific induction of IL-22 in human subjects that resolved HCV infection. Future Virol 2012. [PMID: 23185211 DOI: 10.2217/fvl.12.58] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
AIMS: To determine if in vitro production of IL-22 and IL-17 correlated with resolution of HCV infection. MATERIALS #ENTITYSTARTX00026; METHODS: Human peripheral blood cells isolated from a well-defined cohort of resolved and chronic HCV-infected subjects were used to measure HCV-, influenza- and mitogen-activated T-cell proliferation. In addition, IL-22 and IL-17 production was measured via ELISAs and flow cytometry. RESULTS: Resolved HCV subjects had a significantly higher T-cell proliferative response to recombinant NS3 protein compared with chronic HCV subjects. Resolved subjects had a dose-dependent IL-22 response to recombinant NS3 compared with chronic HCV subjects. CONCLUSION: IL-22 production is associated with antigen-specific induction of CD4 (+) T cells in individuals that resolved HCV infection, suggesting a potential role for IL-22 in HCV clearance.
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Affiliation(s)
- Matthew F Cusick
- Department of Pathology, University of Utah School of Medicine, 30 North 1900 East, 3R330 SOM, Salt Lake City, UT 84132, USA
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45
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Allison RD, Conry-Cantilena C, Koziol D, Schechterly C, Ness P, Gibble J, Kleiner DE, Ghany MG, Alter HJ. A 25-year study of the clinical and histologic outcomes of hepatitis C virus infection and its modes of transmission in a cohort of initially asymptomatic blood donors. J Infect Dis 2012; 206:654-61. [PMID: 22740714 DOI: 10.1093/infdis/jis410] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND A total of 738 volunteer blood donors who were positive for anti-hepatitis C virus (HCV) were assessed for risk factors and outcomes for up to 15 years within the study and up to 54 years from the estimated onset of infection. METHODS A third-generation recombinant immunoblot assay (RIBA) was performed to distinguish true from false anti-HCV reactivity. Findings of HCV polymerase chain reaction classified subjects as having chronic HCV infection or as having recovered. Liver biopsy specimens were staged by Ishak fibrosis score and graded by histologic activity index. RESULTS Of 738 anti-HCV-positive subjects, 469 (64%) had positive RIBA results, 217 (29%) had negative results, and 52 (7%) had indeterminate results. Primary independent risk factors were injection drug use (odds ratio [OR], 35.0; P < .0001), blood transfusion (OR, 9.9; P < .0001), and intranasal cocaine use, including 79 "snorters" who repeatedly denied injection drug use or blood transfusion (OR, 8.5; P < .0001). Classification and regression tree and random forest analyses confirmed these risk factors. A total of 384 RIBA-positive donors (82%) were HCV RNA positive; of these, liver biopsy specimens from 185 (48%) showed no fibrosis in 33%, mild fibrosis in 52%, bridging fibrosis in 12%, and cirrhosis in 2% a mean duration of 25 years after infection. Analysis of 63 repeat biopsy specimens showed that 8% progressed ≥2 Ishak stages over 5 years (mean progression, 0.06 Ishak stages/year). CONCLUSIONS Injection drug use and blood transfusion before 1990 are dominant risk factors for HCV acquisition; intranasal cocaine use may be a surreptitious route of parenteral spread. After a mean of 25 years of HCV infection, histologic outcomes were relatively mild: 85% had no or mild fibrosis, and only 2% had cirrhosis. Nearly one-fifth spontaneously recovered.
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Affiliation(s)
- Robert D Allison
- Department of Transfusion Medicine, National Institutes of Health, Bethesda, MD, USA
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46
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Robinson JL, Doucette K. The natural history of hepatitis C virus infection acquired during childhood. Liver Int 2012; 32:258-70. [PMID: 22098487 DOI: 10.1111/j.1478-3231.2011.02633.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2011] [Accepted: 08/02/2011] [Indexed: 12/23/2022]
Abstract
BACKGROUND The outcome of patients with hepatitis C virus (HCV) infection acquired during childhood in the absence of antiviral therapy is not clear. AIMS The purpose of this study was to review the outcome of untreated HCV acquired in childhood. Only population-based studies were included, as referred cases would be predicted to have more severe disease. METHODS A systematic review of the literature was completed up to October 2010 to identify studies where a population was screened for HCV infection that was presumably acquired during childhood. Demographical and clinical data were collected on infected patients who had not been treated with an antiviral. Primary outcome was development of a severe adverse outcome (cirrhosis, hepatoma, need for a liver transplant or liver-related death). RESULTS There were 25 studies reporting a total of 733 infected patients. Liver biopsy results were provided for 180 patients (25%), revealing cirrhosis in eight (1.0% of the total and 4.0% of those who had a biopsy). None of the other patients developed a severe adverse outcome. As a result of the small number of patients with a severe adverse outcome, risk factors for HCV progression could not be identified. CONCLUSION Although HCV can lead to liver transplantation and death during childhood, the vast majority of patients with disease acquired during childhood have slowly progressive disease. There is no clear indication for antiviral therapy in the majority of children with HCV infection.
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Affiliation(s)
- Joan L Robinson
- Department of Pediatrics, University of Alberta, Edmonton, Canada.
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Li H, Atkins E, Bruckner J, McArdle S, Qiu WC, Thomassen LV, Scott J, Shuhart MC, Livingston S, Townshend-Bulson L, McMahon BJ, Harris M, Griffin S, Gretch DR. Genetic and functional heterogeneity of the hepatitis C virus p7 ion channel during natural chronic infection. Virology 2012; 423:30-7. [DOI: 10.1016/j.virol.2011.11.011] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2011] [Revised: 08/01/2011] [Accepted: 11/11/2011] [Indexed: 01/19/2023]
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Raghwani J, Thomas XV, Koekkoek SM, Schinkel J, Molenkamp R, van de Laar TJ, Takebe Y, Tanaka Y, Mizokami M, Rambaut A, Pybus OG. Origin and evolution of the unique hepatitis C virus circulating recombinant form 2k/1b. J Virol 2012; 86:2212-2220. [PMID: 22114341 PMCID: PMC3302385 DOI: 10.1128/jvi.06184-11] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2011] [Accepted: 11/14/2011] [Indexed: 02/06/2023] Open
Abstract
Since its initial identification in St. Petersburg, Russia, the recombinant hepatitis C virus (HCV) 2k/1b has been isolated from several countries throughout Eurasia. The 2k/1b strain is the only recombinant HCV to have spread widely, raising questions about the epidemiological background in which it first appeared. In order to further understand the circumstances by which HCV recombinants might be formed and spread, we estimated the date of the recombination event that generated the 2k/1b strain using a Bayesian phylogenetic approach. Our study incorporates newly isolated 2k/1b strains from Amsterdam, The Netherlands, and has employed a hierarchical Bayesian framework to combine information from different genomic regions. We estimate that 2k/1b originated sometime between 1923 and 1956, substantially before the first detection of the strain in 1999. The timescale and the geographic spread of 2k/1b suggest that it originated in the former Soviet Union at about the time that the world's first centralized national blood transfusion and storage service was being established. We also reconstructed the epidemic history of 2k/1b using coalescent theory-based methods, matching patterns previously reported for other epidemic HCV subtypes. This study demonstrates the practicality of jointly estimating dates of recombination from flanking regions of the breakpoint and further illustrates that rare genetic-exchange events can be particularly informative about the underlying epidemiological processes.
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Affiliation(s)
- Jayna Raghwani
- Institute of Evolutionary Biology, University of Edinburgh, Ashworth Laboratories, Edinburgh, United Kingdom
| | - Xiomara V. Thomas
- Academic Medical Center, Department of Medical Microbiology, Section of Clinical Virology, Amsterdam, The Netherlands
| | - Sylvie M. Koekkoek
- Academic Medical Center, Department of Medical Microbiology, Section of Clinical Virology, Amsterdam, The Netherlands
| | - Janke Schinkel
- Academic Medical Center, Department of Medical Microbiology, Section of Clinical Virology, Amsterdam, The Netherlands
| | - Richard Molenkamp
- Academic Medical Center, Department of Medical Microbiology, Section of Clinical Virology, Amsterdam, The Netherlands
| | - Thijs J. van de Laar
- VU University Medical Centre, Department of Medical Microbiology and Infection Control, Amsterdam, The Netherlands
| | - Yutaka Takebe
- AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan
| | - Yasuhito Tanaka
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Masashi Mizokami
- The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan
| | - Andrew Rambaut
- Institute of Evolutionary Biology, University of Edinburgh, Ashworth Laboratories, Edinburgh, United Kingdom
- Fogarty International Center, National Institutes of Health, Bethesda, Maryland, USA
| | - Oliver G. Pybus
- Department of Zoology, University of Oxford, Oxford, United Kingdom
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Abdel-Moneim AS, Bamaga MS, Shehab GMG, Abu-Elsaad AASA, Farahat FM. HCV infection among Saudi population: high prevalence of genotype 4 and increased viral clearance rate. PLoS One 2012; 7:e29781. [PMID: 22253780 PMCID: PMC3258249 DOI: 10.1371/journal.pone.0029781] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2011] [Accepted: 12/05/2011] [Indexed: 12/31/2022] Open
Abstract
HCV is a major etiological agent of liver disease with a high rate of chronic evolution. The virus possesses 6 genotypes with many subtypes. The rate of spontaneous clearance among HCV infected individuals denotes a genetic determinant factor. The current study was designed in order to estimate the rate of HCV infection and ratio of virus clearance among a group of infected patients in Saudi Arabia from 2008 to 2011. It was additionally designed to determine the genotypes of the HCV in persistently infected patients. HCV seroprevalence was conducted on a total of 15,323 individuals. Seropositive individuals were tested by Cobas AmpliPrep/Cobas TaqMan HCV assay to determine the ratio of persistently infected patients to those who showed spontaneous viral clearance. HCV genotyping on random samples from persistently infected patients were conducted based on the differences in the 5'untranslated region (5'UTR). Anti-HCV antibodies were detected in 7.3% of the totally examined sera. A high percentage of the HCV infected individuals experienced virus clearance (48.4%). HCV genotyping revealed the presence of genotypes 1 and 4, the latter represented 97.6% of the tested strains. Evidences of the widespread of the HCV genotype 4 and a high rate of HCV virus clearance were found in Saudi Arabia.
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50
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Chak E, Talal AH, Sherman KE, Schiff ER, Saab S. Hepatitis C virus infection in USA: an estimate of true prevalence. Liver Int 2011; 31:1090-101. [PMID: 21745274 DOI: 10.1111/j.1478-3231.2011.02494.x] [Citation(s) in RCA: 305] [Impact Index Per Article: 21.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The recent National Health and Nutrition Examination Survey (NHANES) sampled only the civilian, non-institutionalized population of USA and may have underestimated the prevalence of hepatitis C virus (HCV) in this country. We searched the database MEDLINE, the Bureau of Justice Statistics, Center for Medicare and Medicaid and individual states Department of Corrections for all epidemiological studies regarding the prevalence of HCV in populations not sampled by the NHANES survey namely the incarcerated, homeless, nursing home residents, hospitalized and those on active military duty. Because of their relatively low frequency in the NHANES sample, we also expanded our search to include healthcare workers and long-term dialysis patients. Although included in the NHANES sample, we also performed searches on drug users (injection and non-injection) and veterans to confirm the findings of the NHANES study. Based on the prevalence of studies identified meeting our inclusion criteria, our most conservative estimates state that there at least 142,761 homeless persons, 372,754 incarcerated persons and 6805 persons on active military duty unaccounted for in the NHANES survey. While the NHANES estimates of drug users (both injection and non-injection) appear to be reasonable, the survey seems to have underestimated the number of HCV-positive veterans. Our most conservative estimates suggest that there are at least 5.2 million persons living with HCV in USA today, approximately 1.9 million of whom were unaccounted for in the NHANES survey.
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Affiliation(s)
- Eric Chak
- Department of Medicine, University of California, Sylmar, CA, USA
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