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Zeng RW, Ong CEY, Ong EYH, Chung CH, Lim WH, Xiao J, Danpanichkul P, Law JH, Syn N, Chee D, Kow AWC, Lee SW, Takahashi H, Kawaguchi T, Tamaki N, Dan YY, Nakajima A, Wijarnpreecha K, Muthiah MD, Noureddin M, Loomba R, Ioannou GN, Tan DJH, Ng CH, Huang DQ. Global Prevalence, Clinical Characteristics, Surveillance, Treatment Allocation, and Outcomes of Alcohol-Associated Hepatocellular Carcinoma. Clin Gastroenterol Hepatol 2024; 22:2394-2402.e15. [PMID: 38987014 DOI: 10.1016/j.cgh.2024.06.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Revised: 05/25/2024] [Accepted: 06/02/2024] [Indexed: 07/12/2024]
Abstract
BACKGROUND Although the burden of alcohol-associated hepatocellular carcinoma (HCC) is increasing with rising alcohol consumption, clinical presentation and outcomes of alcohol-associated HCC have not been systematically assessed. We aimed to determine the prevalence, clinical characteristics, surveillance rates, treatment allocation, and outcomes of alcohol-associated HCC. METHODS Medline and Embase were searched from inception to January 2023. Proportional data were analyzed using a generalized linear mixed model. The odds ratio (OR) or mean difference comparing alcohol-associated HCC and other causes was obtained with pairwise meta-analysis. Survival outcomes were evaluated using a pooled analysis of hazard ratios. RESULTS Of 4824 records identified, 55 articles (86,345 patients) were included. Overall, 30.4% (95% confidence interval [CI], 24.0%-37.7%) of HCC was alcohol associated, with the highest proportion in Europe and the lowest in the Americas. People with alcohol-associated HCC were more likely male but were similar in age and comorbidities compared with other causes. A total of 20.8% (95% CI, 11.4%-34.9%) of people with alcohol-associated HCC underwent surveillance compared with 35.0%, 31.6%, and 21.4% in hepatitis B virus, hepatitis C virus, and metabolic dysfunction-associated HCC, respectively (all P < .05). Alcohol-associated HCC had a lower likelihood of Barcelona Clínic Liver Cancer C stage (0/A) (OR, 0.7; 95% CI, 0.6-0.9; P = .018) and curative therapy (24.5% vs 33.9%; OR, 0.7; 95% CI, 0.5-0.9; P = .003), and higher mortality (HR, 1.3; 95% CI, 1.1-1.5; P = .012) when compared with other causes. CONCLUSIONS Alcohol-associated HCC is associated with lower surveillance rates, more advanced BCLC stage, lower likelihood of receiving curative therapy, and poorer survival. These data call for measures to reduce heavy alcohol consumption and improve strategies for effective HCC surveillance in high-risk individuals.
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Affiliation(s)
| | - Christen En Ya Ong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Elden Yen Hng Ong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Charlotte Hui Chung
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Wen Hui Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Jieling Xiao
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | | | - Jia Hao Law
- Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, National University Hospital, Singapore
| | - Nicholas Syn
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Biostatistics & Modelling Domain, Saw Swee Hock School of Public Health, National University of Singapore, Singapore
| | - Douglas Chee
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore
| | - Alfred Wei Chieh Kow
- Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, National University Hospital, Singapore; Division of Surgical Oncology, National University Cancer Institute, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Sung Won Lee
- Division of Hepatology, Department of Internal Medicine, Catholic University of Korea, Seoul, Republic of Korea
| | | | - Takumi Kawaguchi
- Department of Digestive Disease Information & Research, School of Medicine, Kurume University, Fukuoka, Japan
| | - Nobuharu Tamaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yock Young Dan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Atsushi Nakajima
- Graduate School of Medicine, Yokohama City University, Yokohama, Japan
| | - Karn Wijarnpreecha
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Arizona College of Medicine, Phoenix, Arizona; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Banner University Medical Center, Phoenix, Arizona
| | - Mark D Muthiah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore
| | | | - Rohit Loomba
- NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, California
| | - George N Ioannou
- Division of Gastroenterology, Department of Medicine, Veterans Affairs Puget Sound Health Care System, Seattle, Washington; Division of Gastroenterology, Department of Medicine, University of Washington, Seattle, Washington
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Cheng Han Ng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Digestive Disease Information & Research, School of Medicine, Kurume University, Fukuoka, Japan
| | - Daniel Q Huang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore.
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Llamosas-Falcón L, Probst C, Buckley C, Jiang H, Lasserre AM, Puka K, Tran A, Rehm J. Sex-specific association between alcohol consumption and liver cirrhosis: An updated systematic review and meta-analysis. FRONTIERS IN GASTROENTEROLOGY (LAUSANNE, SWITZERLAND) 2022; 1:1005729. [PMID: 36926309 PMCID: PMC10016085 DOI: 10.3389/fgstr.2022.1005729] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 03/18/2023]
Abstract
Different studies have shown that females develop liver diseases at lower levels of alcohol consumption than males. Our aim was to quantify the dose-response relationship between alcohol consumption and the risk of liver cirrhosis by sex and identify the differences between females and males. A systematic review was conducted using PubMed/Medline and Embase to identify longitudinal and case-control studies that analyzed the relationship between the level of alcohol use and liver cirrhosis (LC) incidence, and mortality (ICD-8 and ICD-9 codes 571 and ICD-10 codes K70, K73, K74). Pooled relative risks (RR) were calculated by random effects models. Restricted cubic splines were used to model the dose-response relationship. A total of 24 studies were included in the analysis. There were collectively 2,112,476 females and 924,853 males, and a total of 4,301 and 4,231 cases of LC for females and males, respectively. We identified a non-linear dose-response relationship. Females showed a higher risk for LC compared to males with the same amount of alcohol consumed daily. For instance, drinking 40 g/day showed RRs of 9.35 (95% CI 7.64-11.45) in females and 2.82 (95% CI 2.53-3.14) in males, while drinking 80 g/day presented RRs of 23.32 (95% CI 18.24-29.82) in females and 7.93 (95% CI 7.12-8.83) in males. Additional analyses showed that a higher risk for females was found for morbidity and for mortality. Understanding the influence of sex on the association of alcohol consumption and the risk of LC is needed to develop recommendations and clinical guidelines for prevention and treatment. Systematic Review Registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022299680, identifier CRD42022299680.
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Affiliation(s)
- Laura Llamosas-Falcón
- Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - Charlotte Probst
- Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Heidelberg Institute of Global Health, Medical Faculty and University Hospital, Heidelberg, Germany
- Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
| | - Charlotte Buckley
- Department of Automatic Control and Systems Engineering, University of Sheffield, Sheffield, United Kingdom
| | - Huan Jiang
- Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
| | - Aurélie M. Lasserre
- Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Addiction Medicine, Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland
| | - Klajdi Puka
- Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Department of Epidemiology and Biostatistics, Western University, London, ON, Canada
| | - Alexander Tran
- Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - Jürgen Rehm
- Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
- Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
- Institute of Clinical Psychology and Psychotherapy & Center of Clinical Epidemiology and Longitudinal Studies (CELOS), Technische Universität Dresden, Dresden, Germany
- Center for Interdisciplinary Addiction Research (ZIS), Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany
- Faculty of Medicine, Institute of Medical Science, University of Toronto, Toronto, ON, Canada
- Department of International Health Projects, Institute for Leadership and Health Management, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation, Russia
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Abassa KK, Wu XY, Xiao XP, Zhou HX, Guo YW, Wu B. Effect of alcohol on clinical complications of hepatitis virus-induced liver cirrhosis: a consecutive ten-year study. BMC Gastroenterol 2022; 22:130. [PMID: 35305565 PMCID: PMC8934474 DOI: 10.1186/s12876-022-02198-w] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Accepted: 03/04/2022] [Indexed: 12/12/2022] Open
Abstract
Background and aims Although coexisting alcohol-induced liver disease and hepatitis B or C virus-induced liver cirrhosis (ALD + HBV or ALD + HCV) has been the center of recent hepatology researches, numerous controversies still persist. This study aimed to showcase the influence of alcohol on the laboratory values and on the clinical outcomes of patients with hepatitis B and C virus-induced liver cirrhosis. Methods Patients diagnosed with liver cirrhosis (n = 22,287) from January 2010 to December 2019 were enrolled, and divided into five groups according to the etiology: alcohol-induced liver disease (ALD, 1652 cases), hepatitis B virus (HBV, 18,079 cases), hepatitis C virus (HCV, 682 cases), ALD + HBV (1594 cases) and ALD + HCV (280 cases). Laboratory results and proportion of different liver cirrhosis complications were contrasted between groups. Results The proportions of patients with Child Pugh grade C (28.0% vs 18.8%, P < 0.001) or MELD greater than 18 (24.1% vs 18.5%, P < 0.001) in the ALD + HBV group exceeded significantly those in the HBV group. Multivariate logistic regression revealed that the risk of hepatocellular carcinoma (HCC) and that of esophageal gastric variceal bleeding (EGVB) in the ALD + HBV group was respectively 2.01-fold and 1.74-fold that in the HBV group (HCC: OR = 2.01, 95% CI [1.58–2.55]; EGVB: OR = 1.74, 95% CI [1.30–2.33]) after adjusting for potential confounders. Furthermore, a linear-by-linear analysis test showed a decrease in the risk of HCC and EGVB with the duration of alcohol abstinence. Moreover, patients with both antiviral treatment and alcohol abstinence had the lowest risk of HCC and EGVB (HCC: OR = 0.10, 95% CI [0.05–0.20], P < 0.001; EGVB: OR = 0.17, 95% CI [0.06–0.45], P < 0.001) compared to those without any treatment, those with abstinence alone and those with antiviral therapy alone. Similar pattern was noticed while comparing the ALD + HCV group to the HCV group. Conclusion Heavy alcohol use increased the severity of liver function impairment and the prevalence of HCC and EGVB in hepatitis virus-induced liver cirrhosis patients. Remarkably, long-term alcohol abstinence coupled with antiviral treatment effectively decreased the risk of HCC and EGVB in these populations. Supplementary Information The online version contains supplementary material available at 10.1186/s12876-022-02198-w.
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Llamosas-Falcón L, Shield KD, Gelovany M, Hasan OSM, Manthey J, Monteiro M, Walsh N, Rehm J. Impact of alcohol on the progression of HCV-related liver disease: A systematic review and meta-analysis. J Hepatol 2021; 75:536-546. [PMID: 33892007 DOI: 10.1016/j.jhep.2021.04.018] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2020] [Revised: 04/02/2021] [Accepted: 04/08/2021] [Indexed: 12/20/2022]
Abstract
BACKGROUND & AIMS Despite a marked reduction in new cases of cirrhosis caused by HCV infection, over 500,000 new cirrhosis cases in this category were estimated globally in 2019. This contribution quantifies the relationship between alcohol use and the progression of liver disease in people with HCV infections. METHODS The causal impact of different levels of alcohol use on cirrhosis has previously been established. The quantification of this relationship was undertaken based on a systematic search of the literature and a meta-analysis. We limited our search to longitudinal and case-control studies with biologically verified outcomes. Different sensitivity analyses were conducted to check on key assumptions and on the generalizability of the relationship. RESULTS Alcohol use has a dose-dependent relationship with incident cirrhosis, which is linear on the log-linear level, and thus exponential on the level of odds ratios or other risk indicators. Each standard drink of 12 grams of pure alcohol per day increases the risk by about 11%. The results were stable regardless of the statistical model used, level of adjustment, quality of the study, or outcome (i.e., cirrhosis, decompensated cirrhosis, liver-related death). CONCLUSIONS Alcohol use has a marked impact on the progression of HCV infections to cirrhosis and more severe liver outcomes. LAY SUMMARY Alcohol consumption has a significant impact on the progression of liver disease in people with HCV infections. Each alcoholic drink per day is associated with an increase in the risk of cirrhosis of 11%.
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Affiliation(s)
- Laura Llamosas-Falcón
- Preventive Medicine and Public Health, Hospital Universitario 12 de Octubre, Avda de Córdoba s/n, 28041 - Madrid, Spain; Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, Ontario, Canada, M5S 2S1
| | - Kevin D Shield
- Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, Ontario, Canada, M5S 2S1; Dalla Lana School of Public Health, University of Toronto, 155 College Street, Toronto, ON, M5T 1P8, Canada; World Health Organization / Pan American Health Organization Collaborating Centre, Centre for Addiction and Mental Health, 33 Ursula Franklin Street, Toronto, Ontario, Canada, M5S 2S1
| | - Maya Gelovany
- Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, Ontario, Canada, M5S 2S1
| | - Omer S M Hasan
- Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, Ontario, Canada, M5S 2S1; Dalla Lana School of Public Health, University of Toronto, 155 College Street, Toronto, ON, M5T 1P8, Canada
| | - Jakob Manthey
- Center for Interdisciplinary Addiction Research (ZIS), Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf (UKE), Martinistraße 52, 20246 Hamburg, Germany; Institute of Clinical Psychology and Psychotherapy & Center of Clinical Epidemiology and Longitudinal Studies (CELOS), Technische Universität Dresden, Chemnitzer Str. 46, 01187 Dresden, Germany; Department of Psychiatry, Medical Faculty, University of Leipzig, Semmelweisstraße 10, 04103 Leipzig, Germany
| | - Maristela Monteiro
- Pan American Health Organization/ WHO Regional Office for the Americas, 525 23rd St, Washington DC 20037, USA
| | - Nick Walsh
- Pan American Health Organization/ WHO Regional Office for the Americas, 525 23rd St, Washington DC 20037, USA
| | - Jürgen Rehm
- Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, Ontario, Canada, M5S 2S1; Dalla Lana School of Public Health, University of Toronto, 155 College Street, Toronto, ON, M5T 1P8, Canada; World Health Organization / Pan American Health Organization Collaborating Centre, Centre for Addiction and Mental Health, 33 Ursula Franklin Street, Toronto, Ontario, Canada, M5S 2S1; Center for Interdisciplinary Addiction Research (ZIS), Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf (UKE), Martinistraße 52, 20246 Hamburg, Germany; Institute of Clinical Psychology and Psychotherapy & Center of Clinical Epidemiology and Longitudinal Studies (CELOS), Technische Universität Dresden, Chemnitzer Str. 46, 01187 Dresden, Germany; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, Ontario, Canada, M5T 2S1; Faculty of Medicine, Institute of Medical Science, University of Toronto, Medical Sciences Building, 1 King's College Circle, Room 2374, Toronto, Ontario, Canada, M5S 1A8; Department of Psychiatry, University of Toronto, 250 College Street, 8th Floor, Toronto, Ontario, Canada, M5T 1R8; Department of International Health Projects, Institute for Leadership and Health Management, I.M. Sechenov First Moscow State Medical University, Trubetskaya str., 8, b. 2, 119992, Moscow, Russian Federation.
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Alberca RW, Rigato PO, Ramos YÁL, Teixeira FME, Branco ACC, Fernandes IG, Pietrobon AJ, Duarte AJDS, Aoki V, Orfali RL, Sato MN. Clinical Characteristics and Survival Analysis in Frequent Alcohol Consumers With COVID-19. Front Nutr 2021; 8:689296. [PMID: 34150832 PMCID: PMC8206498 DOI: 10.3389/fnut.2021.689296] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 04/29/2021] [Indexed: 12/15/2022] Open
Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can generate a systemic disease named coronavirus disease-2019 (COVID-19). Currently, the COVID-19 pandemic has killed millions worldwide, presenting huge health and economic challenges worldwide. Several risk factors, such as age, co-infections, metabolic syndrome, and smoking have been associated with poor disease progression and outcomes. Alcohol drinking is a common social practice among adults, but frequent and/or excessive consumption can mitigate the anti-viral and anti-bacterial immune responses. Therefore, we investigated if patients with self-reported daily alcohol consumption (DAC) presented alteration in the immune response to SARS-CoV-2. We investigated 122 patients with COVID-19 (101 male and 46 females), in which 23 were patients with DAC (18 men and 5 women) and 99 were non-DAC patients (58 men and 41 women), without other infections, neoplasia, or immunodeficiencies. Although with no difference in age, patients with DAC presented an increase in severity-associated COVID-19 markers such as C-reactive protein (CRP), neutrophil count, and neutrophil-to-lymphocyte ratio. In addition, patients with DAC presented a reduction in the lymphocytes and monocytes counts. Importantly, the DAC group presented an increase in death rate in comparison with the non-DAC group. Our results demonstrated that, in our cohort, DAC enhanced COVID-19-associated inflammation, and increased the number of deaths due to COVID-19.
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Affiliation(s)
- Ricardo Wesley Alberca
- Laboratorio de Dermatologia e Imunodeficiencias (LIM-56), Departamento de Dermatologia, Faculdade de Medicina FMUSP, Instituto de Medicina Tropica, Universidade de São Paulo, São Paulo, Brazil
| | - Paula Ordonhez Rigato
- Technical Division of Medical Biology, Immunology Center, Adolfo Lutz Institute, São Paulo, Brazil
| | - Yasmim Álefe Leuzzi Ramos
- Laboratorio de Dermatologia e Imunodeficiencias (LIM-56), Departamento de Dermatologia, Faculdade de Medicina FMUSP, Instituto de Medicina Tropica, Universidade de São Paulo, São Paulo, Brazil
| | - Franciane Mouradian Emidio Teixeira
- Laboratorio de Dermatologia e Imunodeficiencias (LIM-56), Departamento de Dermatologia, Faculdade de Medicina FMUSP, Instituto de Medicina Tropica, Universidade de São Paulo, São Paulo, Brazil.,Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Anna Cláudia Calvielli Branco
- Laboratorio de Dermatologia e Imunodeficiencias (LIM-56), Departamento de Dermatologia, Faculdade de Medicina FMUSP, Instituto de Medicina Tropica, Universidade de São Paulo, São Paulo, Brazil.,Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Iara Grigoletto Fernandes
- Laboratorio de Dermatologia e Imunodeficiencias (LIM-56), Departamento de Dermatologia, Faculdade de Medicina FMUSP, Instituto de Medicina Tropica, Universidade de São Paulo, São Paulo, Brazil
| | - Anna Julia Pietrobon
- Laboratorio de Dermatologia e Imunodeficiencias (LIM-56), Departamento de Dermatologia, Faculdade de Medicina FMUSP, Instituto de Medicina Tropica, Universidade de São Paulo, São Paulo, Brazil.,Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Alberto Jose da Silva Duarte
- Laboratorio de Dermatologia e Imunodeficiencias (LIM-56), Departamento de Dermatologia, Faculdade de Medicina FMUSP, Instituto de Medicina Tropica, Universidade de São Paulo, São Paulo, Brazil
| | - Valeria Aoki
- Laboratorio de Dermatologia e Imunodeficiencias (LIM-56), Departamento de Dermatologia, Faculdade de Medicina FMUSP, Instituto de Medicina Tropica, Universidade de São Paulo, São Paulo, Brazil
| | - Raquel Leão Orfali
- Laboratorio de Dermatologia e Imunodeficiencias (LIM-56), Departamento de Dermatologia, Faculdade de Medicina FMUSP, Instituto de Medicina Tropica, Universidade de São Paulo, São Paulo, Brazil
| | - Maria Notomi Sato
- Laboratorio de Dermatologia e Imunodeficiencias (LIM-56), Departamento de Dermatologia, Faculdade de Medicina FMUSP, Instituto de Medicina Tropica, Universidade de São Paulo, São Paulo, Brazil
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Irvin R, Ntiri-Reid B, Kleinman M, Agee T, Hitt J, Anaedozie O, Arowolo T, Cassidy-Stewart H, Bush C, Wilson LE, Millman AJ, Nelson NP, Canary L, Brinkley S, Moon J, Falade-Nwulia O, Sulkowski MS, Thomas DL, Melia MT. Sharing the cure: Building primary care and public health infrastructure to improve the hepatitis C care continuum in Maryland. J Viral Hepat 2020; 27:1388-1395. [PMID: 32671942 PMCID: PMC7721959 DOI: 10.1111/jvh.13360] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Revised: 06/23/2020] [Accepted: 07/01/2020] [Indexed: 12/14/2022]
Abstract
In 2014, trained healthcare provider capacity was insufficient to deliver care to an estimated 70 000 persons in Maryland with chronic hepatitis C virus (HCV) infection. The goal of Maryland Community Based Programs to Test and Cure Hepatitis C, a public health implementation project, was to improve HCV treatment access by expanding the workforce. Sharing the Cure (STC) was a package of services deployed 10/1/14-9/30/18 that included enhanced information technology and public health infrastructure, primary care provider training and practice transformation. Nine primary care sites enrolled. HCV clinical outcomes were documented among individuals who presented for care at sites and met criteria for HCV testing including risk factor or birth cohort (born between 1945 and 1965) based testing. Fifty-three providers completed the STC training. STC providers identified 3237 HCV antibody-positive patients of which 2624 (81%) were RNA+. Of those HCV RNA+, 1739 (66%) were staged, 932 (36%) were prescribed treatment, 838 (32%) started treatment, 721 (27%) completed treatment and 543 (21%) achieved cure. Among 1739 patients staged, 693 (40%) patients had a liver fibrosis assessment score < F2, rendering them ineligible for treatment under Maryland Medicaid guidelines. HCV RNA testing among HCV antibody-positive people increased from 40% (baseline) to 95% among STC providers. Of 554 patients with virologic data reported, 543 (98%) achieved cure. Primary care practices can effectively serve as HCV treatment centers to expand treatment access. However, criteria by insurance providers in Maryland were a major barrier to treatment.
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Affiliation(s)
- Risha Irvin
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Boatemaa Ntiri-Reid
- Infectious Disease Prevention and Health Services Bureau, Maryland Department of Health, Baltimore, MD, United States
| | - Mary Kleinman
- Infectious Disease Prevention and Health Services Bureau, Maryland Department of Health, Baltimore, MD, United States
| | - Tracy Agee
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Jeffrey Hitt
- Infectious Disease Prevention and Health Services Bureau, Maryland Department of Health, Baltimore, MD, United States
| | - Onyeka Anaedozie
- Infectious Disease Prevention and Health Services Bureau, Maryland Department of Health, Baltimore, MD, United States
| | - Tolu Arowolo
- Infectious Disease Prevention and Health Services Bureau, Maryland Department of Health, Baltimore, MD, United States
| | - Hope Cassidy-Stewart
- Infectious Disease Prevention and Health Services Bureau, Maryland Department of Health, Baltimore, MD, United States
| | - CaSaundra Bush
- Infectious Disease Prevention and Health Services Bureau, Maryland Department of Health, Baltimore, MD, United States
| | - Lucy E. Wilson
- Infectious Disease Prevention and Health Services Bureau, Maryland Department of Health, Baltimore, MD, United States
| | - Alexander J. Millman
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, United States
| | - Noele P. Nelson
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, United States
| | - Lauren Canary
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, United States
| | - Sherilyn Brinkley
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Juhi Moon
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Oluwaseun Falade-Nwulia
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Mark S. Sulkowski
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - David L. Thomas
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Michael T. Melia
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, United States
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Irvin R, Chander G, Falade-Nwulia O, Astemborski J, Starbird L, Kirk GD, Sulkowski MS, Thomas DL, Mehta SH. Overlapping epidemics of alcohol and illicit drug use among HCV-infected persons who inject drugs. Addict Behav 2019; 96:56-61. [PMID: 31035079 PMCID: PMC6718047 DOI: 10.1016/j.addbeh.2019.04.023] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Revised: 04/21/2019] [Accepted: 04/22/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Alcohol use in people who inject drugs (PWID) with hepatitis C virus (HCV) infection accelerates liver disease progression. This paper describes the prevalence and associated correlates of alcohol use among HCV antibody positive PWID. METHODS In a large cohort of HCV antibody positive PWID (N = 1623) followed from 2005 to 2013, we characterized alcohol use using the AUDIT-C. We used multivariable logistic regression with generalized estimated equations to examine socio-demographic, clinical, and substance use correlates of alcohol use. RESULTS At their initial visit, 41% reported no, 21% reported moderate, and 38% reported heavy alcohol use. The odds of moderate and heavy alcohol use increased with greater intensity of substance use represented by a composite summary variable which ranged from 0 to 3 substances (street-acquired prescription drugs, non-injection cocaine/heroin, and injection drugs) used. Compared to those who used no drugs, those who used 3 substances had 3.71 odds (95% CI: 3.07-4.48) of moderate alcohol use and 3.65 odds (95% CI: 3.20-4.16) of heavy alcohol use. CONCLUSIONS The prevalence of moderate/heavy alcohol use is high among HCV antibody positive PWID and occurs frequently in combination with other drug use. This may contribute to progressive liver fibrosis thus limiting the gains achieved from HCV cure. Public health interventions need to address the overlapping epidemics of HCV, alcohol use, and other substance use in this population.
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Affiliation(s)
- Risha Irvin
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
| | - Geetanjali Chander
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Oluwaseun Falade-Nwulia
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Jacquie Astemborski
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
| | - Laura Starbird
- Johns Hopkins School of Nursing, Baltimore, MD, United States
| | - Gregory D Kirk
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
| | - Mark S Sulkowski
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - David L Thomas
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
| | - Shruti H Mehta
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
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8
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Gayam V, Tiongson B, Mandal AK, Garlapati P, Pan C, Mohanty S. Real-world study of hepatitis C treatment with direct-acting antivirals in patients with drug abuse and opioid agonist therapy. Scand J Gastroenterol 2019; 54:646-655. [PMID: 31120776 DOI: 10.1080/00365521.2019.1617893] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Background: Limited data exist evaluating the treatment outcomes with direct-acting antivirals (DAAs) in patients with drug use in the community setting. We aim to assess the treatment response of DAAs in this subset of patients with or without the opioid agonist therapy (OAT). Methods: All the hepatitis C virus (HCV) infected patients treated with DAAs were retrospectively analyzed. Patients were stratified into two groups by the presence or absence of abusing alcohol, cocaine and heroin. All the patients who were assigned to the abuser group had positive urine toxicology with one of the drugs during the DAA treatment. The primary assessment was the sustained virologic response (SVR12) at 12 weeks post-treatment (SVR12). Results: Among the 314 patients, 152, 128 and 58 were patients with drug use, non-drug use and receiving OAT. Among the patients with injectable or non-injectable drug use treatment, completion rate was 99% (151/152) and SVR12 was 93.4%. Among the patients with no drug use treatment, completion rate was 95% (122/128) and SVR12 was 88.3%. Among patients receiving OAT alone, SVR12 was 100%, and in patients with OAT + other drug use, SVR12 was 96.5%. None of the patients included in this study discontinued the treatment due to adverse events associated with treatment medications. Conclusions: In this community-based study, DAAs are safe, effective with high overall SVR12 in patients with active drug use (injectable and non-injectable) and OAT enrolled patients. These results support the removal of drug use as a barrier to DAA therapy.
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Affiliation(s)
- Vijay Gayam
- a Department of Medicine and Gastroenterology , Interfaith Medical Center , Brooklyn , NY , USA
| | - Benjamin Tiongson
- a Department of Medicine and Gastroenterology , Interfaith Medical Center , Brooklyn , NY , USA
| | - Amrendra Kumar Mandal
- a Department of Medicine and Gastroenterology , Interfaith Medical Center , Brooklyn , NY , USA
| | - Pavani Garlapati
- a Department of Medicine and Gastroenterology , Interfaith Medical Center , Brooklyn , NY , USA
| | - Calvin Pan
- b Department of Medicine, Division of Gastroenterology and Hepatology , NYU Langone Health, New York University School of Medicine , New York , NY , USA
| | - Smruti Mohanty
- c Department of Medicine and Division of Gastroenterology and Hepatology , New York-Presbyterian Brooklyn Methodist Hospital , Brooklyn , NY , USA
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9
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Evaluation of hepatitis A, B, and C serology in patients with cirrhosis and intensive alcohol consumption. North Clin Istanb 2018; 5:109-113. [PMID: 30374475 PMCID: PMC6191551 DOI: 10.14744/nci.2018.50570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2018] [Accepted: 04/25/2018] [Indexed: 11/20/2022] Open
Abstract
OBJECTIVE The objective of this study was to evaluate the serology of hepatitis A, B, and C in patients with cirrhosis and intensive alcohol consumption. METHODS We retrospectively reviewed the viral serology results of 817 patients with cirrhosis and intensive alcohol consumption who presented to the Gastroenterology Clinic of Atatürk Training and Research Hospital of Izmir Katip Çelebi University between April 2008 and December 2017. The diagnosis of cirrhosis was based on clinical and biochemical evaluations and imaging results. Patients consuming absolute alcohol 40 g/day for >10 years were included and those who quit drinking ≥15 years ago were excluded. RESULTS Of all the patients, 806 (98.7%) were positive for anti-HAV IgG, 159 (19.5%) for HBsAg, and 32 (3.9%) for anti-HCV. Genotyping was performed in 13 patients. Genotype 1 was detected in 10 patients (1a, one patient; 1b, nine patients) and genotype 3 in three patients. Of the patients with HBV, 10.0% had HBeAg and 7.6% had anti-delta. One-hundred and two (12.5%) patients had HCC, and of these, six (5.9%) were HCV-positive and 53 (52.0%) were HBsAg-positive. CONCLUSION Patients with cirrhosis and intensive alcohol consumption have an increased hepatitis B and C prevalence. Patients with chronic viral hepatitis with alcohol habit are at a higher risk for HCC. Therefore, patients with cirrhosis and intensive alcohol consumption should be screened for hepatitis B and C.
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10
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George N, Harrell SM, Rhodes KD, Duarte-Rojo A. Recreational Drug and Psychosocial Profile in Chronic Hepatitis C Patients Seeking Antiviral Therapy. Ann Hepatol 2018; 17:76-84. [PMID: 29311404 DOI: 10.5604/01.3001.0010.7537] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS Practitioners treating hepatitis C (HCV) provide healthcare to a special population with high rates of substance abuse and psychiatric disorders. We investigated the psychosocial profile in HCV patients and tested what variables affect commencement of antiviral therapy. MATERIAL AND METHODS Recreational drug use (RDU), marijuana (THC), alcohol use, and psychiatric history were initially investigated with a questionnaire prior to history and physical. Following an educational intervention, we reinterrogated patients for RDU and THC use, and revision of initial statement was documented. Variables affecting commencement of antiviral therapy were analysed with logistic regression. RESULTS Out of 153 patients, 140 (92%) answered the questionnaire. Intervention increased total yield by 6%, however, 39% (11/28) of those initially denying use revised their statement. Drug screening identified 9 more patients with RDU/THC use. Half of patients consuming alcohol were heavy drinkers, and psychiatric disease was identified in 54%. Only 73 (48%) of 139 patients eligible for antivirals received treatment. Multivariable analysis revealed that younger patients (OR = 1.04, 95% CI 1.01-1.08), and those testing positive on drug screen (OR = 0.41, 95% CI 0.19-0.92) were less likely to be treated. Denial by insurance and loss to follow-up were the most common reasons for not starting antiviral treatment. CONCLUSION Substance abuse is highly prevalent among HCV patients, and it is difficult to tell prior from current users. Integral care of HCV patients should include a diligent screen for substance abuse and rehabilitation referral, aiming to increase the pool of patients eligible for antiviral therapy. This can only be achieved through a multidisciplinary approach.
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Affiliation(s)
- Nayana George
- Department of Internal Medicine. University of Arkansas for Medical Sciences; Little Rock, Arkansas, USA
| | - Sherrie M Harrell
- Division of Gastroenterology and Hepatology. University of Arkansas for Medical Sciences; Little Rock, Arkansas, USA
| | - Kimberly D Rhodes
- Division of Gastroenterology and Hepatology. University of Arkansas for Medical Sciences; Little Rock, Arkansas, USA
| | - Andres Duarte-Rojo
- Division of Gastroenterology and Hepatology. University of Arkansas for Medical Sciences; Little Rock, Arkansas, USA
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11
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The Mexican consensus on the treatment of hepatitis C. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2018. [DOI: 10.1016/j.rgmxen.2017.11.002] [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: 12/09/2022] Open
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12
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Aiza-Haddad I, Ballesteros-Amozurrutia A, Borjas-Almaguer OD, Castillo-Barradas M, Castro-Narro G, Chávez-Tapia N, Chirino-Sprung RA, Cisneros-Garza L, Dehesa-Violante M, Flores-Calderón J, Flores-Gaxiola A, García-Juárez I, González-Huezo MS, González-Moreno EI, Higuera-de la Tijera F, Kershenobich-Stalnikowitz D, López-Méndez E, Malé-Velázquez R, Marín-López E, Mata-Marín JA, Méndez-Sánchez N, Monreal-Robles R, Moreno-Alcántar R, Muñoz-Espinosa L, Navarro-Alvarez S, Pavia-Ruz N, Pérez-Ríos AM, Poo-Ramírez JL, Rizo-Robles MT, Sánchez-Ávila JF, Sandoval-Salas R, Torre A, Torres-Ibarra R, Trejo-Estrada R, Velarde-Ruiz Velasco JA, Wolpert-Barraza E, Bosques-Padilla F. The Mexican consensus on the treatment of hepatitis C. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2018; 83:275-324. [PMID: 29803325 DOI: 10.1016/j.rgmx.2017.11.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/08/2017] [Revised: 10/17/2017] [Accepted: 11/02/2017] [Indexed: 12/12/2022]
Abstract
The aim of the Mexican Consensus on the Treatment of HepatitisC was to develop clinical practice guidelines applicable to Mexico. The expert opinion of specialists in the following areas was taken into account: gastroenterology, infectious diseases, and hepatology. A search of the medical literature was carried out on the MEDLINE, EMBASE, and CENTRAL databases through keywords related to hepatitisC treatment. The quality of evidence was subsequently evaluated using the GRADE system and the consensus statements were formulated. The statements were then voted upon, using the modified Delphi system, and reviewed and corrected by a panel of 34 voting participants. Finally, the level of agreement was classified for each statement. The present guidelines provide recommendations with an emphasis on the new direct-acting antivirals, to facilitate their use in clinical practice. Each case must be individualized according to the comorbidities involved and patient management must always be multidisciplinary.
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Affiliation(s)
| | | | - O D Borjas-Almaguer
- Hospital Universitario «Dr. José Eleuterio González», Monterrey, Nuevo León, México
| | | | - G Castro-Narro
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | | | | | - L Cisneros-Garza
- Centro de Enfermedades Hepáticas del Hospital San José, Monterrey, Nuevo León, México
| | | | - J Flores-Calderón
- Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Ciudad de México, México
| | | | - I García-Juárez
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | | | - E I González-Moreno
- Hospital Universitario «Dr. José Eleuterio González», Monterrey, Nuevo León, México
| | | | | | - E López-Méndez
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - R Malé-Velázquez
- Instituto de Salud Digestiva y Hepática, Guadalajara, Jalisco, México
| | | | - J A Mata-Marín
- Hospital de Infectología del Centro Médico Nacional «La Raza», Ciudad de México, México
| | | | - R Monreal-Robles
- Hospital Universitario «Dr. José Eleuterio González», Monterrey, Nuevo León, México
| | | | - L Muñoz-Espinosa
- Hospital Universitario «Dr. José Eleuterio González», Monterrey, Nuevo León, México
| | | | - N Pavia-Ruz
- Hospital Infantil de México «Federico Gómez», Ciudad de México, México
| | - A M Pérez-Ríos
- Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, México
| | - J L Poo-Ramírez
- Clínica San Jerónimo de Salud Hepática y Digestiva, Ciudad de México, México
| | | | - J F Sánchez-Ávila
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | | | - A Torre
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
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13
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Comparison of ICD-9 Codes for Depression and Alcohol Misuse to Survey Instruments Suggests These Codes Should Be Used with Caution. Dig Dis Sci 2017; 62:2704-2712. [PMID: 28879547 PMCID: PMC5675519 DOI: 10.1007/s10620-017-4714-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2017] [Accepted: 08/07/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND Research suggests depression and alcohol misuse are highly prevalent among chronic hepatitis C (CHC) patients, which is of clinical concern. AIMS To compare ICD-9 codes for depression and alcohol misuse to validated survey instruments. METHODS Among CHC patients, we assessed how well electronic ICD-9 codes for depression and alcohol misuse predicted these disorders using validated instruments. RESULTS Of 4874 patients surveyed, 56% were male and 52% had a history of injection drug use. Based on the PHQ-8, the prevalence of depression was 30% compared to 14% based on ICD-9 codes within 12 months of survey, 37% from ICD-9 codes any time before or within 12 months after survey, and 48% from ICD-9 codes any time before or within 24 months after survey. ICD-9 codes predicting PHQ-8 depression had a sensitivity ranging from 59 to 88% and a specificity ranging from 33 to 65%. Based on the AUDIT-C, the prevalence of alcohol misuse was 21% compared to 3-23% using ICD-9 codes. The sensitivity of ICD-9 codes to predict AUDIT-C score ranged from 9 to 35% and specificity from 80 to 98%. Overall 39% of patients reported ever binge drinking, with a sensitivity of ICD-9 to predict binge drinking ranging from 7 to 33% and a specificity from 84 to 98%. More than half of patients had either an ICD-9 code for depression, a survey score indicating depression, or both (59%); more than one-third had the same patterns for alcohol misuse (36%). CONCLUSIONS ICD-9 codes were limited in predicting current depression and alcohol misuse, suggesting that caution should be exercised when using ICD-9 codes to assess depression or alcohol misuse among CHC patients.
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14
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Osna NA, Donohue TM, Kharbanda KK. Alcoholic Liver Disease: Pathogenesis and Current Management. Alcohol Res 2017; 38:147-161. [PMID: 28988570 PMCID: PMC5513682] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Excessive alcohol consumption is a global healthcare problem. The liver sustains the greatest degree of tissue injury by heavy drinking because it is the primary site of ethanol metabolism. Chronic and excessive alcohol consumption produces a wide spectrum of hepatic lesions, the most characteristic of which are steatosis, hepatitis, and fibrosis/cirrhosis. Steatosis is the earliest response to heavy drinking and is characterized by the deposition of fat in hepatocytes. Steatosis can progress to steatohepatitis, which is a more severe, inflammatory type of liver injury. This stage of liver disease can lead to the development of fibrosis, during which there is excessive deposition of extracellular matrix proteins. The fibrotic response begins with active pericellular fibrosis, which may progress to cirrhosis, characterized by excessive liver scarring, vascular alterations, and eventual liver failure. Among problem drinkers, about 35 percent develop advanced liver disease because a number of disease modifiers exacerbate, slow, or prevent alcoholic liver disease progression. There are still no FDA-approved pharmacological or nutritional therapies for treating patients with alcoholic liver disease. Cessation of drinking (i.e., abstinence) is an integral part of therapy. Liver transplantation remains the life-saving strategy for patients with end-stage alcoholic liver disease.
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Affiliation(s)
- Natalia A Osna
- Natalia A. Osna, Ph.D., is a Research Biologist in the Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, and an Associate Professor in the Department of Internal Medicine, University of Nebraska Medical Center, both in Omaha, Nebraska. Terrence M. Donohue, Jr., Ph.D., is a Research Biochemist in the Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, and a Professor in the Departments of Internal Medicine and Biochemistry and Molecular Biology, University of Nebraska Medical Center, both in Omaha, Nebraska. Kusum K. Kharbanda, Ph.D., is a Research Biologist in the Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, and a Professor in the Departments of Internal Medicine and Biochemistry and Molecular Biology, University of Nebraska Medical Center, both in Omaha, Nebraska
| | - Terrence M Donohue
- Natalia A. Osna, Ph.D., is a Research Biologist in the Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, and an Associate Professor in the Department of Internal Medicine, University of Nebraska Medical Center, both in Omaha, Nebraska. Terrence M. Donohue, Jr., Ph.D., is a Research Biochemist in the Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, and a Professor in the Departments of Internal Medicine and Biochemistry and Molecular Biology, University of Nebraska Medical Center, both in Omaha, Nebraska. Kusum K. Kharbanda, Ph.D., is a Research Biologist in the Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, and a Professor in the Departments of Internal Medicine and Biochemistry and Molecular Biology, University of Nebraska Medical Center, both in Omaha, Nebraska
| | - Kusum K Kharbanda
- Natalia A. Osna, Ph.D., is a Research Biologist in the Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, and an Associate Professor in the Department of Internal Medicine, University of Nebraska Medical Center, both in Omaha, Nebraska. Terrence M. Donohue, Jr., Ph.D., is a Research Biochemist in the Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, and a Professor in the Departments of Internal Medicine and Biochemistry and Molecular Biology, University of Nebraska Medical Center, both in Omaha, Nebraska. Kusum K. Kharbanda, Ph.D., is a Research Biologist in the Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, and a Professor in the Departments of Internal Medicine and Biochemistry and Molecular Biology, University of Nebraska Medical Center, both in Omaha, Nebraska
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15
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Chereji E, Kern S, Fuller B, Morasco BJ, Phelps A, Hauser P. Co-occurring Depression, Chronic Pain and Substance Use Disorders in People with Hepatitis C. ACTA ACUST UNITED AC 2016. [DOI: 10.2174/1874220301603010079] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Chronic infection with Hepatitis C virus (HCV) is common and can result in serious and sometimes fatal liver complications. The impact of HCV on the liver can be further complicated by medical and psychological comorbidities. Depression, substance use, and pain syndromes are frequent co-morbid conditions in people with HCV and diminish functioning, quality of life, and treatment compliance. Understanding the underlying biological mechanisms of these comorbid conditions within the context of HCV may help elucidate factors contributing to their co-occurrence, perhaps mediatedviapro-inflammatory cytokines. The current review provides a synthesis of the literature on depression, substance use disorders and chronic pain in the presence of HCV. The review includes studies conducted with both veteran and civilian populations. The implications for assessment and antiviral treatment of HCV will be considered.
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16
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Rehm J, Greenfield TK, Kerr W. Patterns of Drinking and Mortality from Different Diseases—An Overview. ACTA ACUST UNITED AC 2016. [DOI: 10.1177/009145090603300203] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Alcohol has been linked to a considerable burden of disease worldwide. Recent epidemiological research has shown that dimensions of alcohol exposure other than average volume are causal in the etiology of disease. Based on a systematic, computer-assisted search, this article attempts a qualitative review of this literature. Results show that cardiovascular disease, especially ischaemic heart disease, is linked to patterns of drinking: regular and light to moderate drinking, and drinking with meals are cardioprotective; heavy drinking occasions have been associated with detrimental outcomes and increases in disease risk. For cancers, consumption of spirits is linked to higher risk of cancers of the upper digestive tract. Spirits also may play a particular role in causing liver cirrhosis in addition to heavy drinking occasions. Finally, injuries are especially related to high blood alcohol concentration and to the frequency of heavy drinking occasions. Overall, these findings strongly indicate that alcohol epidemiology should include adequate pattern measures into future research.
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17
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Punzalan CS, Bukong TN, Szabo G. Alcoholic hepatitis and HCV interactions in the modulation of liver disease. J Viral Hepat 2015; 22:769-76. [PMID: 25754333 PMCID: PMC4966284 DOI: 10.1111/jvh.12399] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2014] [Accepted: 01/15/2015] [Indexed: 12/12/2022]
Abstract
Most HCV-infected patients regularly consume alcohol. Alcoholic liver disease (ALD) and chronic hepatitis C virus (HCV) infection together are the most common causes of liver disease worldwide. Although both factors independently cause liver disease, they synergistically promote rapid liver disease progression with devastating outcomes for patients. This review focuses on the prevalence, clinical characteristics and molecular pathophysiologic mechanisms of HCV infection associated with alcohol abuse. Recent findings have centred on the synergistic effect of alcohol and HCV on viral replication, hepatocyte apoptosis, oxidative stress, alcohol-induced 'leaky gut', miR-122 and immune dysregulation. Clinical and basic research findings presented here summarize key scientific findings with the aim of highlighting potential areas for new therapies and identifying ways of optimizing current treatments for alcoholics with HCV infection.
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Affiliation(s)
| | | | - Gyongyi Szabo
- Corresponding Author: Gyongyi Szabo, MD PhD, Department of Medicine, University of Massachusetts Medical School, LRB208, 364 Plantation Street, Worcester, MA 01605. USA; Tel: 00-1-508-856-5275; Fax: 00-1-508-856-4770;
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18
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Darwish SF, El-Bakly WM, El-Naga RN, Awad AS, El-Demerdash E. Antifibrotic mechanism of deferoxamine in concanavalin A induced-liver fibrosis: Impact on interferon therapy. Biochem Pharmacol 2015; 98:231-42. [PMID: 26358138 DOI: 10.1016/j.bcp.2015.09.001] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2015] [Accepted: 09/02/2015] [Indexed: 02/07/2023]
Abstract
Iron-overload is a well-known factor of hepatotoxicity and liver fibrosis, which found to be a common finding among hepatitis C virus patients and related to interferon resistance. We aimed to elucidate the potential antifibrotic effect of deferoxamine; the main iron chelator, and its additional usefulness to interferon-based therapy in concanavalin A-induced immunological model of liver fibrosis. Rats were treated with deferoxamine and/or pegylated interferon-α for 6 weeks. Hepatotoxicity indices, oxidative stress, inflammatory and liver fibrosis markers were assessed. Concanavalin A induced a significant increase in hepatotoxicity indices and lipid peroxidation accompanied with a significant depletion of total antioxidant capacity, glutathione level and superoxide dismutase activity. Besides, it increased CD4(+) T-cells content and the downstream inflammatory cascades, including NF-κB, TNF-α, iNOS, COX-2, IL-6 and IFN-γ. Furthermore, α-SMA, TGF-β1 and hydroxyproline were increased markedly, which confirmed by histopathology. Treatment with either deferoxamine or pegylated interferon-α alone reduced liver fibrosis markers significantly and improved liver histology. However, some of the hepatotoxicity indices and oxidative stress markers did not improve upon pegylated interferon-α treatment alone, besides the remarkable increase in IL-6. Combination therapy of deferoxamine with pegylated interferon-α further improved all previous markers, ameliorated IL-6 elevation, as well as increased hepcidin expression. In conclusion, our study provides evidences for the potent antifibrotic effects of deferoxamine and the underlying mechanisms that involved attenuating oxidative stress and subsequent inflammatory cascade, as well as the production of profibrogenic factors. Addition of deferoxamine to interferon regimen for HCV patients may offer a promising adjuvant modality to enhance therapeutic response.
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Affiliation(s)
- Samar F Darwish
- Central Administration of Pharmaceutical Affairs, Cairo, Egypt
| | - Wesam M El-Bakly
- Pharmacology & Therapeutic Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Reem N El-Naga
- Pharmacology & Toxicology Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| | - Azza S Awad
- Pharmacology & Toxicology Department, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt
| | - Ebtehal El-Demerdash
- Pharmacology & Toxicology Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
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19
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Osna NA, Ganesan M, Kharbanda KK. Hepatitis C, innate immunity and alcohol: friends or foes? Biomolecules 2015; 5:76-94. [PMID: 25664450 PMCID: PMC4384112 DOI: 10.3390/biom5010076] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2014] [Revised: 01/19/2015] [Accepted: 01/24/2015] [Indexed: 02/05/2023] Open
Abstract
Hepatitis C and alcohol are the most widespread causes of liver disease worldwide. Approximately 80% of patients with a history of hepatitis C and alcohol abuse develop chronic liver injury. Alcohol consumption in hepatitis C virus (HCV)-infected patients exacerbates liver disease leading to rapid progression of fibrosis, cirrhosis and even hepatocellular carcinoma. Hepatocytes are the main sites of HCV-infection and ethanol metabolism, both of which generate oxidative stress. Oxidative stress levels affect HCV replication and innate immunity, resulting in a greater susceptibility for HCV-infection and virus spread in the alcoholic patients. In this review paper, we analyze the effects of ethanol metabolism and other factors on HCV replication. In addition, we illustrate the mechanisms of how HCV hijacks innate immunity and how ethanol exposure regulates this process. We also clarify the effects of HCV and ethanol metabolism on interferon signaling-a crucial point for activation of anti-viral genes to protect cells from virus-and the role that HCV- and ethanol-induced impairments play in adaptive immunity which is necessary for recognition of virally-infected hepatocytes. In conclusion, ethanol exposure potentiates the suppressive effects of HCV on innate immunity, which activates viral spread in the liver and finally, leads to impairments in adaptive immunity. The dysregulation of immune response results in impaired elimination of HCV-infected cells, viral persistence, progressive liver damage and establishment of chronic infection that worsens the outcomes of chronic hepatitis C in alcoholic patients.
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Affiliation(s)
- Natalia A Osna
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, 4101 Woolworth Ave, Omaha, NE 68105, USA.
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68105, USA.
| | - Murali Ganesan
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, 4101 Woolworth Ave, Omaha, NE 68105, USA.
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68105, USA.
| | - Kusum K Kharbanda
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, 4101 Woolworth Ave, Omaha, NE 68105, USA.
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68105, USA.
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Abstract
Alcohol consumption is often associated with viral hepatitis. Although alcohol is known to worsen viral liver disease, the interactions between alcohol and viral hepatitis are not fully understood. Molecular alterations in the liver due to alcohol and viral hepatitis include effects on viral replication, increased oxidative stress, cytotoxicity, and a weakened immune response. Clinically, alcohol enhances disease progression and favors induction of primitive liver neoplasm. The use of new antivirals for hepatitis C and well-established drugs for hepatitis B will determine how viral hepatitis can be controlled in a large percentage of these patients. However, alcohol-related liver disease continues to represent a barrier for access to antivirals, and it remains an unresolved health issue.
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Affiliation(s)
- Stefano Gitto
- Dipartimento di Gastroenterologia, Azienda Ospedaliero-Universitaria & University of Modena and Reggio Emilia, Modena, Italy
| | - Giovanni Vitale
- Dipartimento di Scienze Mediche e Chirurgiche, University of Bologna and Dipartimento dell'Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant'Orsola Malpighi, Bologna, Italy
| | - Erica Villa
- Dipartimento di Gastroenterologia, Azienda Ospedaliero-Universitaria & University of Modena and Reggio Emilia, Modena, Italy
| | - Pietro Andreone
- Dipartimento di Scienze Mediche e Chirurgiche, University of Bologna and Dipartimento dell'Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant'Orsola Malpighi, Bologna, Italy
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Gitto S, Vitale G, Villa E, Andreone P. Update on Alcohol and Viral Hepatitis. J Clin Transl Hepatol 2014; 2:228-33. [PMID: 26356547 PMCID: PMC4521233 DOI: 10.14218/jcth.2014.00030] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2014] [Revised: 11/03/2014] [Accepted: 11/03/2014] [Indexed: 12/15/2022] Open
Abstract
Alcohol consumption is often associated with viral hepatitis. Although alcohol is known to worsen viral liver disease, the interactions between alcohol and viral hepatitis are not fully understood. Molecular alterations in the liver due to alcohol and viral hepatitis include effects on viral replication, increased oxidative stress, cytotoxicity, and a weakened immune response. Clinically, alcohol enhances disease progression and favors induction of primitive liver neoplasm. The use of new antivirals for hepatitis C and well-established drugs for hepatitis B will determine how viral hepatitis can be controlled in a large percentage of these patients. However, alcohol-related liver disease continues to represent a barrier for access to antivirals, and it remains an unresolved health issue.
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Affiliation(s)
- Stefano Gitto
- Dipartimento di Gastroenterologia, Azienda Ospedaliero-Universitaria & University of Modena and Reggio Emilia, Modena, Italy
| | - Giovanni Vitale
- Dipartimento di Scienze Mediche e Chirurgiche, University of Bologna and Dipartimento dell'Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant'Orsola Malpighi, Bologna, Italy
| | - Erica Villa
- Dipartimento di Gastroenterologia, Azienda Ospedaliero-Universitaria & University of Modena and Reggio Emilia, Modena, Italy
| | - Pietro Andreone
- Dipartimento di Scienze Mediche e Chirurgiche, University of Bologna and Dipartimento dell'Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant'Orsola Malpighi, Bologna, Italy
- Correspondence to: Pietro Andreone, Dipartimento di Scienze Mediche e Chirurgiche, University of Bologna and Dipartimento dell'Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant'Orsola Malpighi, Padiglione 11, Via Massarenti 9, 40138 Bologna, Italy. Tel: +39-051-6363618, Fax: +39-051-345-806. E-mail:
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Hepatocarcinogenesis in chronic hepatitis C patients achieving a sustained virological response to interferon: significance of lifelong periodic cancer screening for improving outcomes. J Gastroenterol 2014; 49:1504-13. [PMID: 24317936 DOI: 10.1007/s00535-013-0921-z] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2013] [Accepted: 11/22/2013] [Indexed: 02/04/2023]
Abstract
BACKGROUND Due to advances in interferon (IFN) therapy for chronic hepatitis C, most elderly patients, and even many of those with advanced hepatic fibrosis, now achieve a sustained virological response (SVR). However, carcinogenesis remains problematic in these patients. Hence, we aimed to elucidate risk factors for hepatocarcinogenesis in SVR patients and to present an appropriate follow-up protocol for improving outcomes. METHODS We retrospectively studied 562 consecutive SVR patients for a median observation period of 4.8 years. RESULTS Hepatocellular carcinoma was diagnosed in 31 patients (5.5%). Respective cumulative incidences were 3.1, 10.1, and 15.9% at 5, 10, and 15 years after completion of IFN therapy. The proportional hazards model identified moderate or advanced fibrosis stage, advanced age, habitual alcohol consumption, and alpha-fetoprotein elevation as determinants of carcinogenesis, with hazard ratios of 10.7 (p < 0.001), 4.1 (p < 0.01), 3.9 (p < 0.01), and 2.6 (p < 0.05), respectively. Carcinoma was diagnosed in 26% of patients more than 10 years after completion of IFN therapy. Unexpectedly, F2 fibrosis was detected in 42% of these patients. The 5-year survival rate was 93% in the patients who had received periodic cancer screening but only 60% in those who had not. CONCLUSION We recommend that SVR patients be observed at 6-month intervals, at a minimum, to facilitate diagnosis at an early stage, for as long as possible after completion of therapy even if not at an advanced stage of fibrosis.
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Osna NA, Kharbanda KK, Sun Y, Simpson RL, Poluektova LE, Ganesan M, Wisecarver JL, Mercer DF. Ethanol affects hepatitis C pathogenesis: humanized SCID Alb-uPA mouse model. Biochem Biophys Res Commun 2014; 450:773-6. [PMID: 24953695 DOI: 10.1016/j.bbrc.2014.06.048] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2014] [Accepted: 06/11/2014] [Indexed: 02/08/2023]
Abstract
Alcohol consumption exacerbates the course of hepatitis C viral (HCV) infection, worsens outcomes and contributes to the development of chronic infection that exhibits low anti-viral treatment efficiency. The lack of suitable in vivo models makes HCV-ethanol studies very difficult. Here, we examine whether chimeric SCID Alb-uPA mice transplanted with human hepatocytes and infected with HCV develop worsening pathology when fed ethanol. After 5 weeks of feeding, such mice fed chow+water (control) or chow+20% ethanol in water (EtOH) diets mice developed oxidative stress, decreased proteasome activity and increased steatosis. Importantly, HCV(+) mice in the control group cleared HCV RNA after 5 weeks, while the infection persisted in EtOH-fed mice at the same or even higher levels compared with pre-feeding HCV RNA. We conclude that in chimeric SCID Alb-uPA mice, EtOH exposure causes the complex biochemical and histological changes typical for alcoholic liver injury. In addition, ethanol feeding delays the clearance of HCV RNA thereby generating persistent infection and promoting liver injury. Overall, this model is appropriate for conducting HCV-ethanol studies.
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Affiliation(s)
- Natalia A Osna
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA; Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68105, USA.
| | - Kusum K Kharbanda
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA; Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68105, USA
| | - Yimin Sun
- Department of Surgery, University of Nebraska Medical Center, Omaha, NE 68105, USA
| | - Ronda L Simpson
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA; Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68105, USA
| | - Larisa E Poluektova
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA; Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68105, USA
| | - Murali Ganesan
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA; Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68105, USA
| | - James L Wisecarver
- Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68105, USA
| | - David F Mercer
- Department of Surgery, University of Nebraska Medical Center, Omaha, NE 68105, USA
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Junaid SA, Agina SE, Abubakar KA. Epidemiology and associated risk factors of hepatitis e virus infection in plateau state, Nigeria. Virology (Auckl) 2014; 5:15-26. [PMID: 25512696 PMCID: PMC4251053 DOI: 10.4137/vrt.s15422] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2014] [Revised: 04/21/2014] [Accepted: 04/22/2014] [Indexed: 12/22/2022] Open
Abstract
A cross-sectional study in Nigeria was undertaken to determine the epidemiology, seroprevalence, and associated risk factors, of hepatitis E virus (HEV). A total of 462 subjects were used for the study, categorized into four groups: apparently healthy persons, pregnant women, HIV positive subjects, and animal handlers. Information was obtained from subjects using interviewer-administered questionnaire. Blood samples were collected and analyzed for HEV antibodies (IgG and IgM) using enzyme-linked immunosorbent assay (ELISA) technique. Results obtained were analyzed using Statistical Package for Social Sciences (SPSS) version 17.0 statistical software. The overall seroprevalence of IgG and IgM was 42.7 and 0.9%, respectively. Animal handlers had the highest seroprevalence (66.7%). The associated risk factors for IgM seroprevalence were rural dwelling (P = 0.039, odds ratio (OR) 3.3, 95% confidence interval (CI) 0.7–15.4), blood transfusion (P < 0.001, OR 9.6, 95% CI 2.6–35.6), attending to animals (P = 0.032, OR 4.9, 95% CI 0.9–26.6), and waste disposal (P < 0.001). Factors associated with IgG were age (P = 0.044), location (P < 0.001), marital status (P < 0.001), formal education (P < 0.001), farming as occupation (P < 0.001), rural dwelling (P = 0.001), waste disposal (P < 0.001), alcohol consumption (P = 0.001, OR 2.4, 95% CI 1.4–4.0), open defecation (P < 0.001, OR 2.9, 95% CI 1.4–5.7), attending to animals (P < 0.001, OR 2.3, 95% CI 1.6–3.4), consuming unwashed fruits/vegetables (P < 0.001, OR 4.2, 95% CI 0.3–54.1), and stream/river as a source of drinking water (P < 0.001, OR 3.6, 95% CI 1.6–7.8). Preventive public health measures should be reinforced among all communities, particularly domestic animal handlers and pregnant women. Potable water should be provided for all communities. Data suggest that HEV remains an under-recognized and significant public health problem, warranting further attention and research.
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Affiliation(s)
- Surajudeen A Junaid
- Applied Microbiology Unit, Department of Plant Science and Technology, Faculty of Natural Sciences, University of Jos, Nigeria. ; Department of Medical Microbiology, Federal College of Veterinary and Medical Laboratory Technology, National Veterinary Research Institute (NVRI), Vom, Nigeria
| | - Samuel E Agina
- Applied Microbiology Unit, Department of Plant Science and Technology, Faculty of Natural Sciences, University of Jos, Nigeria
| | - Khadijah A Abubakar
- Department of Medical Virology, Federal College of Veterinary and Medical Laboratory Technology, National Veterinary Research Institute (NVRI), Vom, Nigeria
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Trapero-Marugán M, Moreno-Otero R. Letter: impact of mild alcohol consumption in chronic hepatitis C treatment. Aliment Pharmacol Ther 2013; 37:1118-9. [PMID: 23656425 DOI: 10.1111/apt.12321] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2013] [Accepted: 04/05/2013] [Indexed: 12/13/2022]
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Costentin CE, Trabut JB, Mallet V, Darbeda S, Thépot V, Nalpas B, Badin de Montjoye B, Lavielle B, Vallet-Pichard A, Sogni P, Pol S. Management of hepatitis C virus infection in heavy drinkers. Alcohol Alcohol 2013; 48:337-42. [PMID: 23518789 DOI: 10.1093/alcalc/agt020] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
AIM Optimal management of hepatitis C virus (HCV) infection is controversial in heavy drinkers. We compared the management of HCV infection of heavy drinkers with that of patients without a history of alcohol abuse. METHODS In a retrospective case-control study, 69 HCV-infected heavy drinkers [daily alcohol consumption at referral above 60 g/day, hereafter 'alcohol group'] were compared with matched HCV-infected patients with low alcohol consumption (<40 g/day, 'control group'). RESULTS Patients of the 'alcohol group' were younger (42 vs. 45 years, P = 0.05), more often male (69.6 vs. 56.5%, P = 0.11) and had been infected by intravenous drug use (85.5 vs. 45.0%, P < 0.0001). The percentage of patients with a recommendation for treatment according to the French 2002 consensus (bridging fibrosis or genotype 2 or 3) was 52 of 69 (75.4%) in both groups, while the proportion of patients treated was higher in the control group (71.0 vs. 44.9%, P = 0.002). In the 'alcohol group', patients had better access to treatment if they were employed or consumed 170 g/day or less at first referral. Sustained virological response (SVR) was obtained in 10 of 31 patients (32.3%) of the 'alcohol group' vs. 8 of 31 patients (25.8%) of the control group matched for genotype and type of treatment (P = 0.58). CONCLUSION Heavy drinkers are less often considered for antiviral therapy compared with patients without a history of alcohol abuse. However, once treatment is actually initiated, SVR rates are comparable with those achieved in non-drinkers despite the continuation of alcohol consumption during therapy in some patients.
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Affiliation(s)
- Charlotte E Costentin
- Unité d’Hépatologie et d’Addictologie, Hôpital Cochin, Assistance Publique des Hôpitaux de Paris, 27 rue du faubourg Saint Jacques, 75014 Paris, France
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Magnetic resonance-guided laser-induced thermotherapy in patients with oligonodular hepatocellular carcinoma: long-term results over a 15-year period. J Clin Gastroenterol 2012; 46:796-801. [PMID: 22955262 DOI: 10.1097/mcg.0b013e3182641806] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
GOALS To prospectively evaluate the therapeutic potential of magnetic resonance (MR)-guided laser-induced thermotherapy (LITT) in patients with oligonodular hepatocellular carcinoma. STUDY A total of 113 patients with 175 intrahepatic lesions were treated with MR-guided LITT. The Nd-YAG laser fiber was introduced with a percutaneously positioned irrigated laser application system. Qualitative and quantitative MR parameters and clinical data were evaluated. Survival data were calculated using the Kaplan-Meier method. RESULTS All patients tolerated the procedure well under local anesthesia. The total procedure time was 90 minutes. All observed complications were minor and no further treatment was necessary. Online MR thermometry allowed exact visualization of the extension of laser-induced changes and their relationship to the neighboring anatomy. Lesions up to 2 cm in diameter could be efficiently treated with a single laser application; larger lesions were treated with a dual, triple, and quadruple simultaneous application. In 98% of the patients we achieved a complete necrosis of the tumor and up to 5 mm of safety margin. The mean survival rate for all patients, with calculation started on the date of diagnosis of the HCC nodules treated with LITT, was 4.9 years (95% confidence interval, 3.6, 5.1). The median survival rate for all patients, with calculation started on the date of diagnosis of the HCC nodules treated with LITT, was 3.5 years (95% confidence interval, 2.7, 4.2). One-year survival was 95%; 2-year survival 72%, 3-year survival 54%; and 5-year survival 30%. CONCLUSIONS In intrahepatic oligonodular involvement of hepatocellular carcinoma LITT appears to be an effective therapeutic procedure.
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Masuzaki R, Tateishi R, Yoshida H, Arano T, Uchino K, Enooku K, Goto E, Nakagawa H, Asaoka Y, Kondo Y, Goto T, Ikeda H, Shiina S, Omata M, Koike K. Assessment of disease progression in patients with transfusion-associated chronic hepatitis C using transient elastography. World J Gastroenterol 2012; 18:1385-90. [PMID: 22493553 PMCID: PMC3319966 DOI: 10.3748/wjg.v18.i12.1385] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2011] [Revised: 08/01/2011] [Accepted: 01/22/2012] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the relationship between liver stiffness and duration of infection in blood transfusion-associated hepatitis C virus (HCV) patients with or without hepatocellular carcinoma (HCC). METHODS Between December 2006 and June 2008, a total of 524 transfusion-associated HCV-RNA positive patients with or without HCC were enrolled. Liver stiffness was obtained noninvasively by using Fibroscan (Echosens, Paris, France). The date of blood transfusion was obtained by interview. Duration of infection was derived from the interval between the date of blood transfusion and the date of liver stiffness measurement (LSM). Patients were stratified into four groups based on the duration of infection (17-29 years; 30-39 years; 40-49 years; and 50-70 years). The difference in liver stiffness between patients with and without HCC was assessed in each group. Multiple linear regression analysis was used to determine the factors associated with liver stiffness. RESULTS A total of 524 patients underwent LSM. Eight patients were excluded because of unsuccessful measurements. Thus 516 patients were included in the current analysis (225 with HCC and 291 without). The patients were 244 men and 272 women, with a mean age of 67.8 ± 9.5 years. The median liver stiffness was 14.3 kPa (25.8 in HCC group and 7.6 in non-HCC group). The patients who developed HCC in short duration of infection were male dominant, having lower platelet count, with a history of heavier alcohol consumption, showing higher liver stiffness, and receiving blood transfusion at an old age. Liver stiffness was positively correlated with duration of infection in patients without HCC (r = 0.132, P = 0.024) but not in patients with HCC (r = -0.103, P = 0.123). Liver stiffness was significantly higher in patients with HCC than in those without in each duration group (P < 0.0001). The factors significantly associated with high liver stiffness in multiple regression were age at blood transfusion (P < 0.0001), duration of infection (P = 0.0015), and heavy alcohol consumption (P = 0.043). CONCLUSION Although liver stiffness gradually increases over time, HCC develops in patients with high stiffness value regardless of the duration of infection.
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Drumright LN, Hagan H, Thomas DL, Latka MH, Golub ET, Garfein RS, Clapp JD, Campbell JV, Bonner S, Kapadia F, Thiel TK, Strathdee SA. Predictors and effects of alcohol use on liver function among young HCV-infected injection drug users in a behavioral intervention. J Hepatol 2011; 55:45-52. [PMID: 21145862 PMCID: PMC3094600 DOI: 10.1016/j.jhep.2010.10.028] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2010] [Revised: 10/06/2010] [Accepted: 10/07/2010] [Indexed: 01/16/2023]
Abstract
BACKGROUND & AIMS Hepatitis C virus (HCV) screening can provide opportunities to reduce disease progression through counseling against alcohol use, but empirical data on this issue are sparse. We determined the efficacy of a behavioral intervention in reducing alcohol use among young, HCV-infected injection drug users (IDUs) (n=355) and assessed whether changes in liver enzymes were associated with changes in alcohol consumption. METHODS Both the intervention and attention-control groups were counseled to avoid alcohol use, but the intervention group received enhanced counseling. Logistic regression, ANOVA, and continuous time Markov models were used to identify factors associated with alcohol use, changes in mean ALT and AST levels, and change in alcohol use post-intervention. RESULTS Six months post-intervention, alcohol abstinence increased 22.7% in both groups, with no difference by intervention arm. Transition from alcohol use to abstinence was associated with a decrease in liver enzymes, with a marginally greater decrease in the intervention group (p=0.05 for ALT; p=0.06 for AST). In multivariate Markov models, those who used marijuana transitioned from alcohol abstinence to consumption more rapidly than non-users (RR=3.11); those who were homeless transitioned more slowly to alcohol abstinence (RR=0.47); and those who had ever received a clinical diagnosis of liver disease transitioned more rapidly to abstinence (RR=1.88). CONCLUSIONS Although, behavioral counseling to reduce alcohol consumption among HCV-infected IDUs had a modest effect, reductions in alcohol consumption were associated with marked improvements in liver function. Interventions to reduce alcohol use among HCV-infected IDUs may benefit from being integrated into clinical care and monitoring of HCV infection.
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Affiliation(s)
- Lydia N. Drumright
- At the time of work on study: University of California, San Diego, Department of Medicine, Division of Global Public Health, La Jolla, CA; Current affiliation: Centre for Infection Prevention and Management, Division of Infectious Diseases and Immunology, Department of Medicine, Imperial College London, London, United Kingdom
| | - Holly Hagan
- National Development and Research Institute, Center for Drug Use and HIV Research, New York, NY
| | | | - Mary H. Latka
- At the time of the study: Center for Urban Epidemiologic Studies, New York Academy of Medicine, New York, NY; Current affiliation: The Aurum Institute, Johannesburg, South Africa
| | | | - Richard S. Garfein
- University of California, San Diego, Department of Medicine, Division of Global Public Health, La Jolla, CA
| | - John D. Clapp
- Center for Alcohol and Drug Studies, School of Social Work, San Diego State University, San Diego, CA
| | - Jennifer V. Campbell
- At the time of the study: Seattle-King County Department of Public Health, HIV/AIDS Prevention Program, Seattle, WA
| | - Sebastian Bonner
- Center for Urban Epidemiologic Studies, New York Academy of Medicine
| | - Farzana Kapadia
- At the time of the study: Center for Urban Epidemiologic Studies, New York Academy of Medicine, New York, NY, Current affiliation: New York University, Community Public Health Program New York, NY
| | | | - Steffanie A. Strathdee
- University of California, San Diego, Department of Medicine, Division of Global Public Health, La Jolla, CA
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Fuster D, Tor J, Rey-Joly C, Muga R. [Pathogenic interactions between alcohol and hepatitis C]. Med Clin (Barc) 2011; 138:627-32. [PMID: 21696783 DOI: 10.1016/j.medcli.2011.04.019] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2011] [Revised: 04/08/2011] [Accepted: 04/14/2011] [Indexed: 02/08/2023]
Affiliation(s)
- Daniel Fuster
- Servicio de Medicina Interna, Hospital Universitari Germans Trias i Pujol, Badalona. Universitat Autònoma de Barcelona, Barcelona, España.
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Li S, Liu H, Jin Y, Lin S, Cai Z, Jiang Y. Metabolomics study of alcohol-induced liver injury and hepatocellular carcinoma xenografts in mice. J Chromatogr B Analyt Technol Biomed Life Sci 2011; 879:2369-75. [PMID: 21763219 DOI: 10.1016/j.jchromb.2011.06.018] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2011] [Revised: 06/03/2011] [Accepted: 06/08/2011] [Indexed: 12/16/2022]
Abstract
Alcohol abuse is one of the major causes of liver injury and a promoter for hepatocellular carcinoma (HCC). To understand the disease-associated metabolic changes, we investigated and compared the profiles of metabolites in nude mice with alcohol-induced liver injury or bearing a HCC xenograft (HCCX). Alcohol-induced liver injury was achieved by daily administration of grain liquor, and HCC xenografts were generated by subcutaneous inoculation of HepG2 cells in nude mice. Metabolites in serum samples were profiled by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS). The acquired data was analyzed by principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) to identify potential disease-specific biomarkers. Results showed that the phosphatidylcholine (PC) levels were significantly higher in both liver injury and HCCX mice compared with the control. Interestingly, lysophosphatidylcholines (LPCs) that contain saturated or monounsaturated fatty acids were reduced in both liver injury and HCCX mice, but polyunsaturated fatty acids LPCs were elevated in liver injury mice only. These data delineated the disease-related metabolic alterations of LPCs in liver injury and HCC, suggesting that the LPC profile in serum may be biomarkers for these two common liver diseases.
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Affiliation(s)
- Shangfu Li
- Department of Chemistry, Tsinghua University, Beijing 100084, PR China
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Osna NA, Thomes PG, Jr TMD. Involvement of autophagy in alcoholic liver injury and hepatitis C pathogenesis. World J Gastroenterol 2011; 17:2507-14. [PMID: 21633655 PMCID: PMC3103808 DOI: 10.3748/wjg.v17.i20.2507] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2011] [Revised: 03/23/2011] [Accepted: 03/30/2011] [Indexed: 02/06/2023] Open
Abstract
This review describes the principal pathways of macroautophagy (i.e. autophagy), microautophagy and chaperone-mediated autophagy as they are currently known to occur in mammalian cells. Because of its crucial role as an accessory digestive organ, the liver has a particularly robust autophagic activity that is sensitive to changes in plasma and dietary components. Ethanol consumption causes major changes in hepatic protein and lipid metabolism and both are regulated by autophagy, which is significantly affected by hepatic ethanol metabolism. Ethanol exposure enhances autophagosome formation in liver cells, but suppresses lysosome function. Excessive ethanol consumption synergizes with hepatitis C virus (HCV) to exacerbate liver injury, as alcohol-consuming HCV patients frequently have a longer course of infection and more severe manifestations of chronic hepatitis than abstinent HCV patients. Alcohol-elicited exacerbation of HCV infection pathogenesis is related to modulation by ethanol metabolism of HCV replication. Additionally, as part of this mechanism, autophagic proteins have been shown to regulate viral (HCV) replication and their intracellular accumulation. Because ethanol induces autophagosome expression, enhanced levels of autophagic proteins may enhance HCV infectivity in liver cells of alcoholics and heavy drinkers.
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Abstract
Alcoholic liver disease (ALD) is the second commonest indication for liver transplantation after viral hepatitis in the United States and Europe. Controversies surround the indications and allocation of scarce and expensive resource for this so called self inflicted disease. Controversies stem from the apprehension that alcoholic recipients are likely to relapse and cause damage to the graft. There is a need to select those candidates with lower risk for relapse with the available predictive factors and scores. Substance abuse specialist and psychiatrists are mandatory in the pre-transplant evaluation and in the post-transplant follow-up. There is conflicting evidence to support a fixed period of pretransplant abstinence, although most units do follow this. Alcoholic hepatitis (AH) continues to be a contraindication for transplantation, however there is a need for further research in this field as a subset of patients with AH who do not respond to medical treatment, have high early mortality and could benefit from transplantation. One year, 3-year, and 5-year survival post-transplant is similar for both ALD and non-ALD recipients. The incidence of post-transplant rejection and retransplantation is also similar to other recipients. ALD with viral hepatitis especially hepatitis C virus leads to a more aggressive liver disease with early presentation for transplantation. ALD patients are more prone to develop de-novo malignancy; this is attributed to the long term effect of alcohol, tobacco combined with immunosuppression. Post-transplant surveillance is important to detect early relapse to alcoholism, presence of de-novo malignancy and treat the same adequately.
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McCartney EM, Beard MR. Impact of alcohol on hepatitis C virus replication and interferon signaling. World J Gastroenterol 2010. [PMID: 20238400 DOI: 10.3748/wjg.16.1337] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) is one of the main etiological factors responsible for liver disease worldwide. It has been estimated that there are over 170 million people infected with HCV worldwide. Of these infected individuals, approximately 75% will go on to develop a life long necroinflammatory liver disease, which over decades, can result in serious complications, such as cirrhosis and hepatocellular carcinoma. Currently there is no effective vaccine and whilst antiviral therapies have been improved, they are still only effective in approximately 50% of individuals. HCV infection stands as a major cause of global morbidity and suffering, and places a significant burden on health systems. The second highest cause of liver disease in the western world is alcoholic liver disease. Frequently, HCV infected individuals consume alcohol, and the combined effect of HCV and alcohol consumption is deleterious for both liver disease and response to treatment. This review discusses the impact of alcohol metabolism on HCV replication and the negative impact on interferon (IFN)-alpha treatment, with a particular focus on how alcohol and HCV act synergistically to increase oxidative stress, ultimately leading to exacerbated liver disease and a reduction in the efficacy of IFN-alpha treatment. A better understanding of the complicated mechanisms at play in hepatocytes infected with HCV and metabolizing alcohol will hopefully provide better treatment options for chronic hepatitis C individuals that consume alcohol.
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Affiliation(s)
- Erin M McCartney
- Centre for Cancer Biology, Hanson Centre, Adelaide, South Australia, 5000, Australia
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35
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Abstract
Hepatitis C virus (HCV) is one of the main etiological factors responsible for liver disease worldwide. It has been estimated that there are over 170 million people infected with HCV worldwide. Of these infected individuals, approximately 75% will go on to develop a life long necroinflammatory liver disease, which over decades, can result in serious complications, such as cirrhosis and hepatocellular carcinoma. Currently there is no effective vaccine and whilst antiviral therapies have been improved, they are still only effective in approximately 50% of individuals. HCV infection stands as a major cause of global morbidity and suffering, and places a significant burden on health systems. The second highest cause of liver disease in the western world is alcoholic liver disease. Frequently, HCV infected individuals consume alcohol, and the combined effect of HCV and alcohol consumption is deleterious for both liver disease and response to treatment. This review discusses the impact of alcohol metabolism on HCV replication and the negative impact on interferon (IFN)-α treatment, with a particular focus on how alcohol and HCV act synergistically to increase oxidative stress, ultimately leading to exacerbated liver disease and a reduction in the efficacy of IFN-α treatment. A better understanding of the complicated mechanisms at play in hepatocytes infected with HCV and metabolizing alcohol will hopefully provide better treatment options for chronic hepatitis C individuals that consume alcohol.
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36
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Hakeem L, Thomson GA, Bhattacharyya DN. Epidemiological Survey of Hepatitis C Virus Infection in Fife, Scotland. Gastroenterology Res 2009; 2:282-288. [PMID: 27956972 PMCID: PMC5139775 DOI: 10.4021/gr2009.10.1316] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/14/2009] [Indexed: 11/04/2022] Open
Abstract
Background HCV infection is of growing public health importance in Scotland. We aim to establish: patient demographics; risk category; year/country of probable infection; referral/follow-up status; and genotypic variance of HCV in Fife. Methods Details of all HCV antibody positive patients, referred and assessed at specialist clinics in NHS Fife, until 1st of May 2007 were obtained retrospectively from the Fife hepatitis C database. Results In these patients, the ratio of males: female was 2:1, mean age was 36 years, representing a relatively young population, 27.4% of the patients consumed alcohol and 52.4% were smokers. Twelve patients were HIV/HCV co-infected (3.3%). Among the patients, 6.8% had serological evidence of past HBV exposure, 0.5% of patients were HCV/HBV co-infected and 18.8% were vaccinated. Eighty-six percent acquired HCV through injecting drug use and most cases were relatively newly acquired. Referral numbers were on the increase. Thirty-three of patients were under follow-up. Sixty-five percent of patients were genotype 2/3 and 35% were Genotype 1. Conclusions Clear patterns were observed in terms of age group, gender, geographical distribution and risk category to facilitate the effective targeting of resources. HCV population in Fife are relatively young, have acquired HCV recently and are mostly of genotype 2/3. This may have a favourable influence on disease progression and cost implications of treating HCV in Fife.
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Affiliation(s)
- Lukman Hakeem
- Infectious Diseases Unit, Victoria Hospital (NHS Fife), Kirkcaldy, Fife, United Kingdom, KY2 5AH, UK
| | - Grace A Thomson
- Infectious Diseases Unit, Victoria Hospital (NHS Fife), Kirkcaldy, Fife, United Kingdom, KY2 5AH, UK
| | - Diptendu N Bhattacharyya
- Infectious Diseases Unit, Victoria Hospital (NHS Fife), Kirkcaldy, Fife, United Kingdom, KY2 5AH, UK
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Mueller S, Millonig G, Seitz HK. Alcoholic liver disease and hepatitis C: A frequently underestimated combination. World J Gastroenterol 2009; 15:3462-71. [PMID: 19630099 PMCID: PMC2715970 DOI: 10.3748/wjg.15.3462] [Citation(s) in RCA: 77] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Alcoholic liver disease (ALD) and hepatitis C virus (HCV) infection represent, either alone or in combination, more than two thirds of all patients with liver disease in the Western world. This review discusses the epidemiology and combined impact of ALD and HCV on the progression of liver disease. ALD and HCV affect the progression of liver disease to liver cirrhosis and hepatocellular carcinoma (HCC) in a synergistic manner. Thus, the risk for HCC increases five times with a daily alcohol consumption of 80 g; in the presence of HCV it is increased 20-fold, and a combination of both risk factors leads to a more than 100-fold risk for HCC development. Alcohol consumption also decreases the response to interferon treatment which is probably due to a lack of compliance than a direct effect on HCV replication. Several molecular mechanisms are discussed that could explain the synergistic interaction of alcohol and HCV on disease progression. They include modulation of the immune response and apoptosis, increased oxidative stress via induction of CYP2E1 and the hepatic accumulation of iron. Thus, both HCV and alcohol independently cause hepatic iron accumulation in > 50% of patients probably due to suppression of the liver-secreted systemic iron hormone hepcidin. A better understanding of hepcidin regulation could help in developing novel therapeutic approaches to treat the chronic disease in the future. For now, it can be generally concluded that HCV-infected patients should abstain from alcohol and alcoholics should be encouraged to participate in detoxification programs.
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Musch E, Malek M, von Eick H, Chrissafidou A. Successful Long-term Application of Highly Purified Natural Interferon-alpha (Multiferon®) after Preceding Interferon Approaches in a Chronic Hepatitis C Patient with Thrombocytopenia. ACTA ACUST UNITED AC 2009; 36:395-9. [PMID: 15287392 DOI: 10.1080/00365540410019561] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Treatment approaches with recombinant IFN-alpha2b and natural IFN-beta in a patient with chronic hepatitis C (genotype 1b) and cirrhosis had, in both cases, to be terminated prematurely due to breakthrough phenomena and thrombo-leukocytopenia up to WHO grade 3. After the patient was switched to highly purified natural IFN-alpha (Multiferon) the thrombocyte and leukocyte counts increased significantly, and sustained complete biochemical and virological response could be achieved.
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Affiliation(s)
- Eugen Musch
- Department of General Internal Medicine, Marienhospital Bottrop gGmbH, Germany.
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Karavitis J, Murdoch EL, Gomez CR, Ramirez L, Kovacs EJ. Acute ethanol exposure attenuates pattern recognition receptor activated macrophage functions. J Interferon Cytokine Res 2009; 28:413-22. [PMID: 18597620 DOI: 10.1089/jir.2007.0111] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Both clinical and experimental data have linked acute ethanol exposure to increased susceptibility to infection as well as increased morbidity and mortality after injury. Macrophages play an integral role in the innate immune system and are important in priming the adaptive immune system. In this study, we investigated the effect of a single in vivo exposure of macrophages to physiologically relevant levels of ethanol (1.2 and 2.9 g/kg) followed by ex vivo stimulation with lipopolysaccharide (LPS) or bacteria. Our study confirms the work of others showing that a single administration of ethanol suppresses the production of tumor necrosis factor-alpha(TNF-alpha), interleukin-6 (IL-6), and IL-12 in response to LPS. There was no effect of ethanol on LPS induction of cytokine production at 30 min after treatment. In contrast, at 3 h, both doses of ethanol exposure decreased ex vivo TNF-alpha production by splenic and alveolar macrophages. Interestingly, the higher dose of ethanol resulted in sustained suppression of LPS-induced TNF-alpha production at 3 and 6 h after ethanol administration, as well as decreased IL-6 and IL-12 production after 6 h, as compared to control (saline-treated groups). Alveolar macrophages behaved similarly at 3 h after ethanol treatment. LPS-stimulated production of TNF-alpha and IL-6 was reduced at 3 h after ethanol administration, when compared with the saline-treated animals. Alveolar macrophages stimulated for 3 h with bacteria also showed decreased TNF-alpha and IL-6 production after harvested from mice given 2.9 g/kg ethanol for 3 h. This time point and high dose of ethanol also resulted in decreased Pseudomonas aeruginosa phagocytosis by alveolar macrophages. Taken together, we conclude that the effects of physiological levels of ethanol are dose dependent, have effects that last after ethanol is cleared from the circulation, and can affect multiple macrophage functions.
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Affiliation(s)
- John Karavitis
- Department of Cell Biology, Neurobiology and Anatomy, Loyola University Medical Center, Maywood, IL, USA
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40
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Kerzman H, Green MS, Shinar E. Predictors for non-compliance of notified hepatitis C virus-positive blood donors with recommendation to seek medical counselling. Vox Sang 2009; 96:20-8. [PMID: 19121194 DOI: 10.1111/j.1423-0410.2008.01111.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
BACKGROUND Notification of blood donors represents the commonest method of informing asymptomatic individuals of abnormal test results indicating exposure to hepatitis C virus (HCV) infection. Such notification is therefore important from both health and economic perspectives. This study aimed to identify predictors for non-compliance of HCV-positive blood donors with the National Blood Services recommendation to seek medical counselling. STUDY DESIGN AND METHODS The current research is a cross-sectional study. Telephone interviews were conducted with 201 blood donors identified as HCV positive following blood donation during 2001-2002 (40% response rate). RESULTS About 25% of all the notified blood donors did not seek any counselling; 29% (44/150) of those who requested medical advice from their primary care physicians (general practitoner's) were not referred to specialists. Age, alcohol consumption and non-practice of health-promoting behaviour were independent predictors of non-compliance with the blood services' recommendation. In particular, smoking (odds ratio, 2.0; 95% confidence interval 1.0-4.2) and not undergoing professional teeth cleaning (odds ratio 2.8; 95% confidence interval 1.3-6.1) were found to be significant predictors of non-compliance. CONCLUSION The study provides essential data regarding the extent and risk factors for non-compliance of HCV-positive blood donors with recommendation to seek medical advice. Our results can assist in identifying blood donors who would not seek counselling, based on demographic factors and past exposure to risk factors for HCV. Improvements in the notification process and additional training of general practitoners regarding the management of HCV disease are needed.
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Affiliation(s)
- H Kerzman
- Nursing Division, Chaim Sheba Medical Center, Israel.
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Gitto S, Micco L, Conti F, Andreone P, Bernardi M. Alcohol and viral hepatitis: a mini-review. Dig Liver Dis 2009; 41:67-70. [PMID: 18602355 DOI: 10.1016/j.dld.2008.05.009] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2008] [Revised: 04/29/2008] [Accepted: 05/05/2008] [Indexed: 02/07/2023]
Abstract
Due to their high prevalence in the general population, alcohol use and abuse can be associated with hepatitis B and C virus infections and it has been demonstrated that alcohol plays a role as a co-morbid factor in the development of liver disease. There is evidence that alcohol abuse accelerates the progression of liver fibrosis and affects the survival of patients with chronic hepatitis C. The mechanism by which alcohol worsens hepatitis C virus-related liver disease has not been fully clarified, but enhanced viral replication, increased oxidative stress, cytotoxicity and impairment of immune response could play a relevant role. Alcohol abuse also seems to reduce both sensitivity to interferon and adherence to treatment. It sounds reasonable to presume that the mechanisms enhancing liver damage in patients affected by hepatitis B are similar to those involved in hepatitis C virus infection. However, more studies are warranted to improve our knowledge about the interaction between alcohol intake and hepatitis B virus infection. In conclusion alcohol abuse is associated with an accelerated progression of liver injury, leading to an earlier development of cirrhosis, higher incidence of hepatocellular carcinoma, and higher mortality. Abstinence could reverse some of these deleterious effects.
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Affiliation(s)
- S Gitto
- Department of Medicine, University of Bologna, Bologna, Italy
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42
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Ishihara R, Tanaka H, Iishi H, Takeuchi Y, Higashino K, Uedo N, Tatsuta M, Yano M, Ishiguro S. Long-term outcome of esophageal mucosal squamous cell carcinoma without lymphovascular involvement after endoscopic resection. Cancer 2008; 112:2166-72. [PMID: 18348303 DOI: 10.1002/cncr.23418] [Citation(s) in RCA: 67] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Esophageal cancer is an aggressive cancer with a reported 3-year survival of 20%. However, early-stage esophageal cancer can be cured by endoscopic resection (ER). The long-term survival of esophageal mucosal squamous cell carcinoma after ER was investigated by calculating the standard mortality rate (SMR). METHODS From January 1995 to December 2004, 110 patients with 138 esophageal mucosal squamous cell carcinomas without lymphovascular involvement were treated by ER. Long-term survival after ER was compared with that in the general population by calculating SMR. Subgroup analysis of patients without second primary cancer diagnosed within 1 year before ER (subgroup A) was also performed. RESULTS A total of 108 patients (98.2%) were followed-up completely, with a mean observation period of 4.7 (0.4-11.3) years. The cumulative 5-year survival rate of all patients and subgroup A was 79.5% and 86.6%, respectively. Overall mortality (SMR, 1.68; 95% confidence interval [CI], 1.05-2.55) and mortality from malignant tumor (SMR, 3.14; 95% CI, 1.79-5.09) was significantly higher than that in the general population. SMR of esophageal cancer was high, although it was not significantly different from that in the general population (SMR, 4.82; 95% CI, 0.06-26.81). In subgroup A overall mortality (SMR, 0.86; 95% CI, 0.41-1.57) was similar to that in the general population. CONCLUSIONS High overall mortality in patients with esophageal mucosal cancer after ER was mainly due to elevated mortality from second primary cancer. Favorable mortality in subgroup A indicates the efficiency of ER as a curative treatment for esophageal mucosal cancer.
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Affiliation(s)
- Ryu Ishihara
- Department of Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari-ku, Osaka, Japan.
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Osna NA, White RL, Krutik VM, Wang T, Weinman SA, Donohue TM. Proteasome activation by hepatitis C core protein is reversed by ethanol-induced oxidative stress. Gastroenterology 2008; 134:2144-52. [PMID: 18549882 PMCID: PMC2517112 DOI: 10.1053/j.gastro.2008.02.063] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2007] [Revised: 02/12/2008] [Accepted: 02/21/2008] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS The proteasome is a major cellular proteinase. Its activity is modulated by cellular oxidants. Hepatitis C core protein and ethanol exposure both cause enhanced oxidant generation. The aim was to investigate whether core protein, by its ability to generate oxidants, alters proteasome activity and whether these alterations are further affected by ethanol exposure. METHODS These interactions were examined in Huh-7 cell lines that expressed inducible HCV core protein and/or constitutive cytochrome P450 2E1 (CYP2E1) and as purified components in a cell-free system. Chymotrypsin-like proteasome activity was measured fluorometrically. RESULTS Proteasome activity in core-positive 191-20 cells was 20% higher than that in core-negative cells and was enhanced 3-fold in CYP2E1-expressing L14 cells. Exposure of core-positive cells to glutathione ethyl ester, catalase, or the CYP2E1 inhibitor diallyl sulfide partially reversed the elevation of proteasome activity in core-positive cells, whereas ethanol exposure suppressed proteasome activity. The results indicate that proteasome activity was up-regulated by low levels of core-induced oxidative stress but down-regulated by high levels of ethanol-elicited stress. These findings were partially mimicked in a cell-free system. Addition of core protein enhanced the peptidase activity of purified 20S proteasome containing the proteasome activator PA28 and was further potentiated by addition of liver mitochondrial and/or microsome fractions. However, proteasome activation was significantly attenuated when fractions were obtained from ethanol-fed animals. CONCLUSIONS HCV core protein interacts with PA28, mitochondrial, and endoplasmic reticulum proteins to cause low levels of oxidant stress and proteasome activation, which is dampened during ethanol metabolism when oxidant generation is higher.
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Affiliation(s)
- Natalia A Osna
- Liver Study Unit, Omaha Veterans Affairs Medical Center, Omaha, Nebraska 68105, USA.
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44
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Neuman MG, Sha K, Esguerra R, Zakhari S, Winkler RE, Hilzenrat N, Wyse J, Cooper CL, Seth D, Gorrell MD, Haber PS, McCaughan GW, Leo MA, Lieber CS, Voiculescu M, Buzatu E, Ionescu C, Dudas J, Saile B, Ramadori G. Inflammation and repair in viral hepatitis C. Dig Dis Sci 2008; 53:1468-87. [PMID: 17994278 DOI: 10.1007/s10620-007-0047-3] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2007] [Accepted: 09/26/2007] [Indexed: 02/07/2023]
Abstract
Hepatitis C viral infection (HCV) results in liver damage leading to inflammation and fibrosis of the liver and increasing rates of hepatic decompensation and hepatocellular carcinoma (HCC). However, the host's immune response and viral determinants of liver disease progression are poorly understood. This review will address the determinants of liver injury in chronic HCV infection and the risk factors leading to rapid disease progression. We aim to better understand the factors that distinguish a relatively benign course of HCV from one with progression to cirrhosis. We will accomplish this task by discussion of three topics: (1) the role of cytokines in the adaptive immune response against the HCV infection; (2) the progression of fibrosis; and (3) the risk factors of co-morbidity with alcohol and human immunodeficiency virus (HIV) in HCV-infected individuals. Despite recent improvements in treating HCV infection using pegylated interferon alpha (PEGIFN-alpha) and ribavirin, about half of individuals infected with some genotypes, for example genotypes 1 and 4, will not respond to treatment or cannot be treated because of contraindications. This review will also aim to describe the importance of IFN-alpha-based therapies in HCV infection, ways of monitoring them, and associated complications.
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Affiliation(s)
- Manuela G Neuman
- In Vitro Drug Safety and Biotechnology, Department of Pharmacology, Biophysics and Global Health, Institute of Drug Research, University of Toronto, Toronto, ON, Canada.
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Kamal A, Cheung R. Positive CAGE screen correlates with cirrhosis in veterans with chronic hepatitis C. Dig Dis Sci 2007; 52:2564-9. [PMID: 17415636 DOI: 10.1007/s10620-006-9668-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2006] [Accepted: 11/07/2006] [Indexed: 12/20/2022]
Abstract
The current study examines the relationship between problem alcohol use and severity of liver disease by self-administered questionnaires using both the CAGE questionnaire and beverage-specific quantity-frequency questions. The cohort consisted of 38 patients with cirrhosis (10 with decompensated liver disease) and 62 with mild fibrosis (stage 0-1), of comparable mean age and estimated duration of infection. Although mean alcohol consumption was similar in both groups, a positive CAGE screen (defined as two or more affirmative answers) was significantly more common among cirrhotics (OR = 5.24; 95% CI, 1.78-15.39) and tended to be associated with decompensated liver disease (OR = 13.3; 95% CI, 0.67-256) among cirrhotics. In multivariate analysis, only inflammatory grade on liver biopsy (OR = 67.7; 95% CI, 10.6-431) and positive CAGE score (OR = 8.09; 95% CI, 1.15-57.1) were independent predictors of cirrhosis. These findings suggest that the CAGE questionnaire predicts advanced liver disease better than daily or lifetime drinking measures.
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Affiliation(s)
- Ahmad Kamal
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California 94305, USA
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46
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Seronello S, Sheikh MY, Choi J. Redox regulation of hepatitis C in nonalcoholic and alcoholic liver. Free Radic Biol Med 2007; 43:869-82. [PMID: 17697932 DOI: 10.1016/j.freeradbiomed.2007.05.036] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2007] [Revised: 05/26/2007] [Accepted: 05/30/2007] [Indexed: 12/19/2022]
Abstract
Hepatitis C virus (HCV) is an RNA virus of the Flaviviridae family that is estimated to have infected 170 million people worldwide. HCV can cause serious liver disease in humans, such as cirrhosis, steatosis, and hepatocellular carcinoma. HCV induces a state of oxidative/nitrosative stress in patients through multiple mechanisms, and this redox perturbation has been recognized as a key player in HCV-induced pathogenesis. Studies have shown that alcohol synergizes with HCV in the pathogenesis of liver disease, and part of these effects may be mediated by reactive species that are generated during hepatic metabolism of alcohol. Furthermore, reactive species and alcohol may influence HCV replication and the outcome of interferon therapy. Alcohol consumption has also been associated with increased sequence heterogeneity of the HCV RNA sequences, suggesting multiple modes of interaction between alcohol and HCV. This review summarizes the current understanding of oxidative and nitrosative stress during HCV infection and possible combined effects of HCV, alcohol, and reactive species in the pathogenesis of liver disease.
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Affiliation(s)
- Scott Seronello
- School of Natural Sciences, University of California at Merced, Merced, CA 95344, USA
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47
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Abstract
BACKGROUND Since the discovery of the hepatitis C virus (HCV), extensive literature has emerged on alcohol and HCV interaction. GOAL To understand the impact of alcohol and HCV infection on the severity of liver disease and the mechanisms of interaction between the two. STUDY Of 1269 articles (1991 to 2006) searched through MEDLINE and cited cross references, 133 were thoroughly reviewed to assess: (a) prevalence of combined alcohol use and HCV, (b) severity of liver disease (c) treatment response, and (d) mechanisms of interaction between HCV and alcohol. Data on study design, patient demographics, diagnostic tests used, and study outcomes were extracted for critical analysis. RESULTS Prevalence of HCV is 3-fold to 30-fold higher in alcoholics compared with the general population. Patients with HCV infection and alcohol abuse develop more severe fibrosis with higher rate of cirrhosis and hepatocellular cancer compared with nondrinkers. Increased oxidative stress seems to be the dominant mechanism for this synergism between alcohol and the HCV. Abstinence is the key to the management of liver disease due to HCV and alcohol. Data have shown that lower response rates to interferon in alcoholics with HCV infection are likely due to noncompliance. CONCLUSIONS Alcoholics with HCV infection have more severe liver disease compared with nondrinkers. Patients should be encouraged to enroll in rehabilitation programs so as to improve treatment adherence and response.
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Affiliation(s)
- Ashwani K Singal
- James J Peters Bronx Veterans Affairs Medical Center, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10468, USA.
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de Vasconcelos RR, Tengan FM, Cavalheiro NDP, Ibrahim K, Pereira H, Barone AA. [Factors associated with severe evolutive forms of chronic infection with hepatitis C virus]. Rev Soc Bras Med Trop 2006; 39:433-8. [PMID: 17160319 DOI: 10.1590/s0037-86822006000500003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2005] [Accepted: 07/26/2006] [Indexed: 11/21/2022] Open
Abstract
To assess the factors associated with the development of moderate and severe fibrosis, the medical records of 426 patients with chronic hepatitis C virus infection attended at the Infectious and Parasitic Diseases Clinic of the University of São Paulo Faculty of Medicine from January 1 to December 31, 2000 were reviewed. Of the patients included in the study, 56.3% were male and 43.7%, female. Patient age ranged from 18 to 69 years. Blood transfusion was the most frequent form of hepatitis C virus transmission, detected in 128 (30%) cases, and no risk factor was detected in 187 (43.9%) patients. Patient distribution regarding architectural changes observed in a liver biopsy was: grade 0 (14.1%); grade 1 (51.2%); grade 2 (20.6%); grade 3 (8%); grade 4 (6.1%). Multivariate analysis revealed a positive correlation between fibrosis severity and age greater than 40 years at the time of the liver biopsy, serum albumin levels below normal lower limits, gamma-glutamyltransferase levels equal to or higher than twice upper normal limits, platelet numbers less than 150,000/mm(3) and high necroinflammatory activity. The data obtained were inconclusive regarding a possible correlation between severity of fibrosis and alcoholism.
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Manolakopoulos S, Economou M, Bethanis S, Mathou N, Triantos C, Vlachogiannakos J, Vogiatzakis E, Avgerinos A, Tzourmakliotis D. A single alcohol ingestion does not affect serum hepatitis C virus RNA in patients with chronic hepatitis C. Liver Int 2006; 26:1196-200. [PMID: 17105584 DOI: 10.1111/j.1478-3231.2006.01360.x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND AIM The safe level of alcohol ingestion in sporadic drinkers with hepatitis C is unknown. Our aim was to evaluate the effect of a single moderate alcohol intake on serum HCV RNA concentrations and hepatic function in patients with chronic HCV infection. METHODS Twenty-one patients with chronic hepatitis C were randomly assigned to consume 50 g alcohol (group 1) or a non-alcoholic beverage (group 2). In both groups, serum ethanol, serum HCV RNA, transaminase and gamma-glutamyltranspeptidase (gamma-GT) levels were measured just before alcohol intake and after 1, 2, 8, 24 h and 1 week's time. RESULTS The maximum concentration of ethanol in the blood was observed at the first hour after alcohol intake. No significant changes were observed in serum HCV RNA after alcohol intake. Repeated measurements of HCV RNA among the two groups revealed no difference (P = 0.215). Similarly, no difference was observed in transaminase and gamma-GT levels at different time points in each group or among the groups [(ALT (P = 0.082), AST (P = 0.33), gamma-GT (P = 0.538)]. CONCLUSIONS In patients with chronic hepatitis C, a single intake of 50 g alcohol does not affect liver biochemistry and HCV RNA concentrations. Therefore, it is a matter of further research whether sporadic drinking of light or moderate amounts of alcohol should be avoided in patients with chronic hepatitis C.
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50
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Carrière M, Rosenberg AR, Conti F, Chouzenoux S, Terris B, Sogni P, Soubrane O, Calmus Y, Podevin P. Low density lipoprotein receptor transcripts correlates with liver hepatitis C virus RNA in patients with alcohol consumption. J Viral Hepat 2006; 13:633-42. [PMID: 16907851 DOI: 10.1111/j.1365-2893.2006.00737.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Alcohol consumption has a major impact on the natural history of chronic hepatitis C virus (HCV) infection, although the underlying mechanisms are still debated. We designed a clinical study to evaluate the impact of alcohol abuse on both viral load and expression of low-density lipoprotein receptor (LDLR) and CD81 expression. Thirty-eight consecutive HCV-infected patients were enrolled. Group 1 (n = 18), < or =10 g alcohol/day, group 2 (n = 8), < or =30 g alcohol/day, group 3 (n = 12), >or =30 g alcohol/day. Receptors expression was measured by flow cytometry analysis in peripheral blood mononuclear cells (PBMC) and by specific real-time retrotranscription polymerase chain reaction (RT-PCR) in the liver. Serum viral load was evaluated by quantification of both HCV genomic RNA and total core antigen. The hepatic viral load was assessed by real-time RT-PCR. Serum HCV-RNA and total core antigen were significantly correlated, and were higher, albeit not significantly, in group 3 than in group 1. Alcohol consumption had no effect on expression of HCV putative receptors in PBMC, except for CD81, which was upregulated on monocytes in group 2. In the liver, viral load and levels of LDLR transcripts were significantly higher in group 3 than in group 1. Remarkably, a significant positive correlation was found between LDLR transcripts and HCV-RNA (r2 = 0.83, P < 10(-3)). Finally, in vitro experiments suggested that the effect of ethanol on LDLR expression was indirectly mediated by both tumour necrosis factor-alpha and interleukin-1beta. In conclusion, this study is the first to support a role for LDLR in the natural infection by HCV in man.
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MESH Headings
- Adult
- Alcohol Drinking
- Antigens, CD/biosynthesis
- Antigens, CD/genetics
- Flow Cytometry
- Gene Expression Profiling
- Hepacivirus/genetics
- Hepacivirus/isolation & purification
- Hepacivirus/physiology
- Hepatitis C, Chronic/genetics
- Hepatitis C, Chronic/metabolism
- Hepatitis C, Chronic/virology
- Humans
- Leukocytes, Mononuclear/chemistry
- Liver/metabolism
- Liver/virology
- Male
- Middle Aged
- RNA, Viral/analysis
- RNA, Viral/blood
- Receptors, LDL/biosynthesis
- Receptors, LDL/genetics
- Receptors, Virus/genetics
- Receptors, Virus/metabolism
- Reverse Transcriptase Polymerase Chain Reaction
- Statistics as Topic
- Tetraspanin 28
- Transcription, Genetic
- Viral Load
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Affiliation(s)
- M Carrière
- UPRESS 1833, Faculté de Médecine Paris V, France
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