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Tan CH, Chang MC, Tsai WF, Chuang WL, Huang JF, Lin ZY, Dai CY, Yeh ML, Li CT, Yu RL. Different profiles of neurocognitive impairment in patients with hepatitis B and C virus infections. Sci Rep 2022; 12:10625. [PMID: 35739162 PMCID: PMC9226189 DOI: 10.1038/s41598-022-14736-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Accepted: 06/13/2022] [Indexed: 11/20/2022] Open
Abstract
The direct impact of chronic hepatitis B and hepatitis C on neurocognition remains elusive due to the frequent comorbidities, and the domains of the neurocognitive functions affected have rarely been investigated comprehensively. We cross-sectionally assessed the neurocognitive functions of the individuals with chronic hepatitis B, chronic hepatitis C, treated chronic hepatitis C with a sustained virologic response, and their healthy control counterparts. Laboratory examinations were used to investigate the impact of inflammation on neurocognition, exclude the medical conditions that could interfere with neurocognition assessment, and assess liver function and fibrotic severity of the liver of the participants. This study found the detrimental impact of chronic hepatitis B on language and executive functions. In contrast, individuals with chronic hepatitis C showed deficits in executive functions, psychomotor speed, memory, and attention. Successful elimination of hepatitis C resulted in improved liver function, but not neuropsychological test performance. Moreover, erythrocyte sedimentation rate level was found to mediate the deficits in the attention of individuals with chronic hepatitis C. These results demonstrate the neurocognitive deficits and the difference in the profiles of neurocognitive deficits in individuals with chronic hepatitis B and chronic hepatitis C. Our study also provided results suggesting the mediation by systemic inflammation on the attention deficit in individuals with chronic hepatitis C.
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Affiliation(s)
- Chun-Hsiang Tan
- Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Meng-Chia Chang
- Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Wei-Fang Tsai
- M.Sc. Program in Tropical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Zu-Yau Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chi-Ting Li
- Department of Psychology, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Rwei-Ling Yu
- Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
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2
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Ibáñez-Samaniego L, Rapado-Castro M, Cabrero L, Navarrete C, García-Mulas S, Ahumada A, Marquez L, Pérez MD, Rincon D, Bañares R, Garcia-Martinez R. Hepatitis C eradication improves cognitive function in patients with or without cirrhosis: A prospective real-life study. Eur J Neurol 2021; 29:400-412. [PMID: 34634159 DOI: 10.1111/ene.15138] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 10/05/2021] [Accepted: 10/07/2021] [Indexed: 01/23/2023]
Abstract
BACKGROUND AND PURPOSE Hepatitis C virus (HCV) infection is associated with neuropsychiatric disturbances that impact on functioning and health-related quality of life (HRQoL). Reversibility at different liver disease stages is unknown, particularly in cirrhosis. We aimed to evaluate cognition, functioning, and HRQoL following HCV eradication at different liver disease stages. METHODS A random sample (n = 152) of consecutive patients treated with direct-acting antiviral agents (DAAs) between April 2015 and March 2017 were included. A comprehensive neuropsychological assessment, functioning and HRQoL questionnaires were applied at baseline, and 12 and 48 weeks after the end of antivirals. RESULTS One-hundred thirty-five patients who achieved virological response completed the follow-up, of whom 44 had cirrhosis (27% decompensated). Twenty-one percent had cognitive impairment before starting DAAs (34.1% cirrhotic vs. 14.4% noncirrhotic, p < 0.011). Viral eradication was associated with a decrease in cognitive impairment to 23% of cirrhotic and 6% of noncirrhotic patients (p < 0.05). Interestingly, older patients (B = 0.11, 95% confidence interval [CI] = 0.03-0.19) with baseline cognitive impairment (B = 3.58, 95% CI = 1.54-5.62) were those with higher cognitive benefit, regardless of liver disease. Persistent cognitive impairment was associated with having higher cardiovascular risk, cirrhosis, lower education, and higher anxiety and depression scores. Functioning and HRQoL also improved after eradication but remained worse in the cirrhotic group. CONCLUSIONS Viral eradication decreases the prevalence of cognitive impairment and improves functioning and HRQoL. Patients with lower brain reserve (older patients) and baseline cognitive impairment may benefit the most. Identification and treatment of HCV patients through screening programs may reduce the burden of cognitive disturbances beyond the prevention of liver disease progression.
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Affiliation(s)
- Luis Ibáñez-Samaniego
- Hepatology Unit, Department of Digestive Diseases, Gregorio Marañón University General Hospital, Madrid, Spain.,Gregorio Marañón Institute of Health Research, Madrid, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain
| | - Marta Rapado-Castro
- Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Gregorio Marañón University General Hospital, Madrid, Spain.,Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne & Melbourne Health, Carlton, Victoria, Australia.,School of Medicine, Complutense University of Madrid, Madrid, Spain
| | - Lucia Cabrero
- Gregorio Marañón Institute of Health Research, Madrid, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain
| | - Cristina Navarrete
- Hepatology Unit, Department of Digestive Diseases, Gregorio Marañón University General Hospital, Madrid, Spain
| | - Seila García-Mulas
- Hepatology Unit, Department of Digestive Diseases, Gregorio Marañón University General Hospital, Madrid, Spain
| | - Adriana Ahumada
- Hepatology Unit, Department of Digestive Diseases, Gregorio Marañón University General Hospital, Madrid, Spain
| | - Laura Marquez
- Hepatology Unit, Department of Digestive Diseases, Gregorio Marañón University General Hospital, Madrid, Spain
| | - Maria Dolores Pérez
- Hepatology Unit, Department of Digestive Diseases, Gregorio Marañón University General Hospital, Madrid, Spain
| | - Diego Rincon
- Hepatology Unit, Department of Digestive Diseases, Gregorio Marañón University General Hospital, Madrid, Spain.,Gregorio Marañón Institute of Health Research, Madrid, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain.,School of Medicine, Complutense University of Madrid, Madrid, Spain
| | - Rafael Bañares
- Hepatology Unit, Department of Digestive Diseases, Gregorio Marañón University General Hospital, Madrid, Spain.,Gregorio Marañón Institute of Health Research, Madrid, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain.,School of Medicine, Complutense University of Madrid, Madrid, Spain
| | - Rita Garcia-Martinez
- Gregorio Marañón Institute of Health Research, Madrid, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain.,School of Medicine, Complutense University of Madrid, Madrid, Spain.,Department of Internal Medicine, Gregorio Marañon University General Hospital, Madrid, Spain
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3
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Collier ME, Zhang S, Scrutton NS, Giorgini F. Inflammation control and improvement of cognitive function in COVID-19 infections: is there a role for kynurenine 3-monooxygenase inhibition? Drug Discov Today 2021; 26:1473-1481. [PMID: 33609782 PMCID: PMC7889466 DOI: 10.1016/j.drudis.2021.02.009] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 01/26/2021] [Accepted: 02/10/2021] [Indexed: 02/07/2023]
Abstract
The novel respiratory virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), emerged during late 2019 and spread rapidly across the world. It is now recognised that the nervous system can be affected in COVID-19, with several studies reporting long-term cognitive problems in patients. The metabolic pathway of tryptophan degradation, known as the kynurenine pathway (KP), is significantly activated in patients with COVID-19. KP metabolites have roles in regulating both inflammatory/immune responses and neurological functions. In this review, we speculate on the effects of KP activation in patients with COVID-19, and how modulation of this pathway might impact inflammation and reduce neurological symptoms.
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Affiliation(s)
- Mary Ew Collier
- Department of Genetics and Genome Biology, University of Leicester, Leicester LE1 7RH, UK.
| | - Shaowei Zhang
- Manchester Institute of Biotechnology, Department of Chemistry, School of Natural Sciences, The University of Manchester, 131 Princess Street, Manchester M1 7DN, UK
| | - Nigel S Scrutton
- Manchester Institute of Biotechnology, Department of Chemistry, School of Natural Sciences, The University of Manchester, 131 Princess Street, Manchester M1 7DN, UK
| | - Flaviano Giorgini
- Department of Genetics and Genome Biology, University of Leicester, Leicester LE1 7RH, UK
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4
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Direct antivirals and cognitive impairment in hepatitis C: a clinical-neurophysiologic study. J Neurovirol 2020; 26:870-879. [PMID: 32910431 PMCID: PMC7716927 DOI: 10.1007/s13365-020-00904-6] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 08/05/2020] [Accepted: 08/26/2020] [Indexed: 12/26/2022]
Abstract
Cognition was assessed in hepatitis C virus (HCV) patients, who did not meet the criteria for a minimal hepatic encephalopathy. Their liver function was compensated. We then disentangled potential cognitive changes associated with a sustained virologic response at 12 weeks (SVR-12), following treatment with direct antiviral agents (DAAs). We studied 23 selected HCV patients with a battery of standard neuropsychological tests, and with recordings of the P300 wave, a cerebral potential of “cognitive” significance. There was a baseline evaluation (T0) and a second one 6 months later (T1). We had 2 control groups of comparable age and sex, i.e., 15 patients suffering from non-alcoholic fatty liver disease (NAFLD) and 15 healthy subjects. At T0, we detected a significant (p < 0.05) cognitive impairment in the HCV group, which involved episodic and working memory, attention, visuospatial and verbal abilities, executive functions, and logic reasoning. The P300 latency was significantly (p < 0.05) delayed in the group. At T1, we observed some significant (p < 0.05) HCV recovery in given test domains, e.g., memory, executive functions, and reasoning. Accordingly, the P300 latency shortened significantly (p < 0.05). HCV patients exhibited subtle cognitive defects, somehow independent of their liver condition, possibly linked to direct or indirect brain involvement by the virus. These defects partly recovered following the SVR-12, as achieved through DAAs. The P300 wave was a valid neurophysiologic counterpart of these changes. DAAs can have a role in the early preservation of cognition in HCVs.
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5
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The Many Difficulties and Subtleties in the Cognitive Assessment of Chronic Hepatitis C Infection. Int J Hepatol 2020; 2020:9675235. [PMID: 32257447 PMCID: PMC7106929 DOI: 10.1155/2020/9675235] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2019] [Revised: 02/27/2020] [Accepted: 03/10/2020] [Indexed: 12/30/2022] Open
Abstract
Since the discovery of HCV in 1989, several diseases have been related to chronic infection by this virus. Often, patients with hepatitis C virus (HCV) complain of cognitive impairment even before the development of hepatic cirrhosis, which they described as "brain fog." Several studies have proposed a link between chronic HCV infection and the development of cognitive alterations, but the inclusion of confounding factors in their samples significantly limits the analysis of the results. In this article, we will give an overview about cognitive dysfunction in patients with HCV.
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6
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Fortini I, Arouca EMG, Tengam FM, Nitrini R. Chronic HCV infection and neuropsychiatric dysfunction. eNeurologicalSci 2019; 17:100206. [PMID: 31656863 PMCID: PMC6806448 DOI: 10.1016/j.ensci.2019.100206] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2019] [Revised: 08/23/2019] [Accepted: 09/03/2019] [Indexed: 02/06/2023] Open
Abstract
•Cognitive impairment may contribute to the morbidity of chronic HCV infection.•Deficits in memory recall can be found in chronic HCV patients.•There is a lack of correlation between virus genotypes, viral load and cognitive performance.•Minimal hepatic encephalopathy may be present in HCV patients with cognitive impairment.
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Affiliation(s)
- Ida Fortini
- Department of Neurology, University of São Paulo School of Medicine, Avenida Dr. Eneas de Carvalho Aguiar 155, Room n° 5140, 5th floor, ZIP code: 05403-000 Cerqueira César, São Paulo, Brazil
| | - Eustáquio Martins Gomes Arouca
- Department of Neurology, University of São Paulo School of Medicine, Avenida Dr. Eneas de Carvalho Aguiar 155, Room n° 5140, 5th floor, ZIP code: 05403-000 Cerqueira César, São Paulo, Brazil
| | - Fatima Mitiko Tengam
- Hepatitis C Outpatient Clinic, Department of Infectious and Parasitic Diseases, University of São Paulo School of Medicine, Avenida Dr. Eneas de Carvalho Aguiar 155, 4th floor, Cerqueira César, ZIP code: 05403-000 São Paulo, São Paulo, Brazil
| | - Ricardo Nitrini
- Department of Neurology, University of São Paulo School of Medicine, Avenida Dr. Eneas de Carvalho Aguiar 155, Room n° 5140, 5th floor, ZIP code: 05403-000 Cerqueira César, São Paulo, Brazil
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Kuna L, Jakab J, Smolic R, Wu GY, Smolic M. HCV Extrahepatic Manifestations. J Clin Transl Hepatol 2019; 7:172-182. [PMID: 31293918 PMCID: PMC6609844 DOI: 10.14218/jcth.2018.00049] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2018] [Revised: 02/21/2019] [Accepted: 03/17/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) has been shown to affect many tissues other than liver. However, of the many extrahepatic manifestations (EMs) that have been associated with HCV, including cryoglobulinemia, lymphoma, insulin resistance, type 2 diabetes and neurological disorders, only a few have been shown to be directly related to HCV infection of extrahepatic tissues. HCV-triggered immune-mediated mechanisms account for most of the EMs. It is estimated that up to 74% of patients with chronic hepatitis C can develop at least one EM. All HCV patients with EMs should be considered for antiviral therapy, although not all will resolve with sustained virological response.
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Affiliation(s)
- Lucija Kuna
- Department of Pharmacology and Biochemistry, Faculty of Dental Medicine and Health, J. J. Strossmayer University of Osijek, Osijek, Croatia
| | - Jelena Jakab
- Department of Pathophysiology and Physiology with Immunology, Faculty of Dental Medicine and Health, J. J. Strossmayer University of Osijek, Osijek, Croatia
- Department of Internal Medicine, Faculty of Medicine, J. J. Strossmayer University of Osijek, Osijek, Croatia
| | - Robert Smolic
- Department of Pathophysiology and Physiology with Immunology, Faculty of Dental Medicine and Health, J. J. Strossmayer University of Osijek, Osijek, Croatia
- Department of Pharmacology, Faculty of Medicine, J. J. Strossmayer University of Osijek, Osijek, Croatia
| | - George Y Wu
- Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, CT, USA
| | - Martina Smolic
- Department of Pharmacology and Biochemistry, Faculty of Dental Medicine and Health, J. J. Strossmayer University of Osijek, Osijek, Croatia
- Department of Pharmacology, Faculty of Medicine, J. J. Strossmayer University of Osijek, Osijek, Croatia
- *Correspondence to: Martina Smolic, Department of Pharmacology, J. J. Strossmayer University of Osijek Faculty of Medicine Osijek, J. Huttlera 4, Osijek 31000, Croatia. Tel: + 385-31-512-800, Fax: +385-31-512-833, E-mail:
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8
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Mechanisms of neuropathogenesis in HIV and HCV: similarities, differences, and unknowns. J Neurovirol 2018; 24:670-678. [PMID: 30291565 DOI: 10.1007/s13365-018-0678-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2018] [Revised: 08/20/2018] [Accepted: 09/07/2018] [Indexed: 12/17/2022]
Abstract
HIV and hepatitis C virus (HCV) have both been associated with cognitive impairment. Combination antiretroviral therapy (cART) has dramatically changed the nature of cognitive impairment in HIV-infected persons, while the role of direct-acting antivirals (DAA) in neurocognition of HCV-infected individuals remains unclear. Also, whether HIV and HCV interact to promote neurocognitive decline or whether they each contribute an individual effect continues to be an open question. In this work, we review the virally mediated mechanisms of HIV- and HCV-mediated neuropathogenesis, with an emphasis on the role of dual infection, and discuss observed changes with HIV viral suppression and HCV functional cure on neurocognitive impairments.
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9
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Psychiatric and functional neuroimaging abnormalities in chronic hepatitis C virus patients: Is vasculitis a contributing factor? Arab J Gastroenterol 2018; 19:71-75. [PMID: 29935864 DOI: 10.1016/j.ajg.2018.06.003] [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] [Received: 09/05/2017] [Revised: 03/21/2018] [Accepted: 06/05/2018] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND STUDY AIMS Central nervous system (CNS) involvement in hepatitis C virus (HCV) infection has different facets such as anxiety, depression, cognitive impairment and vasculitis. We were interested in detecting subclinical CNS involvement in chronic HCV infected subjects with and without systemic vasculitis. PATIENTS AND METHODS Nineteen patients (15 females and 4 males) with chronic HCV infection (mean age 46.5 ± 7 and mean duration since diagnosis of HCV infection 4.7 ± 4 years, including 6 (32%) Child-Pugh class A cirrhotic patients) and 30 age, sex and education matched healthy control subjects were studied. Thirteen patients had associated vasculitis. Patients and control subjects were assessed using the block design and comprehension subtests of Wechsler Bellevue Adult Intelligence Scale, Wechsler Memory scale (WMS), Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI). Brain HMPAO Single Photon Emission Computed Tomography (SPECT) was performed for HCV patients. RESULTS Patients with HCV had lower scores on the block design test compared to control subjects (8.37 ± 1.89 versus 10.37 ± 1.47, p < 0.001), lower total WMS scores (43.15 ± 10.49 versus 60.27 ± 8.08, p < 0.001) and higher anxiety and depression scores (16.94 ± 10.46 and 37.17 ± 10.38 versus 10.3 ± 4.67 and 28.9 ± 5.99, p = 0.004 and 0.001, respectively). Total WMS were lower in HCV patients with vasculitis compared to those without vasculitis (39.14 ± 9.3 versus 51.17 ± 8.3, p = 0.019) while the block design and comprehension tests, BAI and BDI were not significantly different between both groups. The block design and comprehension tests, WMS, BAI and BDI were not significantly different between cirrhotic and non-cirrhotic patients. Seven patients had different patterns of cerebral hypoperfusion on SPECT, and all of them had associated vasculitis. Abnormal SPECT was associated with lower total WMS scores (35.87 ± 10.8 versus 46.79 ± 8.6 in those with normal SPECT, p = 0.049). CONCLUSIONS Vasculitis may contribute to the development of neuropsychiatric involvement in HCV patients.
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10
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Abstract
Hepatitis C virus (HCV) is the most common blood-borne infection in the United States and is of concern in older adults. HCV infection is associated with not only hepatic but also extrahepatic comorbidities common to the aging patient including diabetes, kidney and cardiovascular diseases, and neurocognitive impairment. The effect of direct-acting antiviral agents to treat HCV on these outcomes is limited. This article summarizes the literature regarding the epidemiology and natural history of HCV infection; the impact of age on clinical outcomes in HCV-infected persons; and current knowledge regarding safety and efficacy of HCV treatment regimens in the older patient.
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Affiliation(s)
- Michael Reid
- Department of Medicine, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94122, USA
| | - Jennifer C Price
- Department of Medicine, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94122, USA
| | - Phyllis C Tien
- Department of Medicine, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94122, USA; Medical Service, Department of Veteran Affairs Medical Center, San Francisco, CA 94121, USA.
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Golfieri L, Gitto S, Morelli MC, Pinna AD, Grandi S, Andreone P. Impact of hepatitis C virus infection on health-related quality of life before and after liver transplantation: a multidisciplinary point of view. Expert Rev Anti Infect Ther 2018; 15:759-765. [PMID: 28756716 DOI: 10.1080/14787210.2017.1362334] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Hepatitis C negatively changes patient quality of life even in the absence of advanced liver disease. The specific patterns of quality of life of hepatitis C positive patients waiting for transplant or after surgery are not widely studied. Areas covered: A significant percentage of infected patients show cognitive impairment, fatigue, and/or a 'brain fog', that cannot be explained by the liver disease. Depression can be diagnosed in one third of hepatitis C positive patients. Conflicting data are available regarding the possible role of Model for End-Stage Liver Disease score as predictor of impaired quality of life. In the first period after liver transplant, quality of life tends to increase at the pre-transplant period but in the medium and long-term period, it declines. The recurrence of hepatitis C infection represents a strong predictor of morbidity and mortality and can significantly affect the global quality of life of patients. Expert commentary: Hepatologists, surgeons and psychologists should collaborate to support infected patients in all phases of transplant including the long-term period after surgery. Education and information should be implemented especially regarding the positive role of new direct antivirals.
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Affiliation(s)
- Lucia Golfieri
- a Dipartimento di Psicologia , Università di Bologna , Bologna , Italy
| | - Stefano Gitto
- b Centro di Ricerca per lo Studio delle Epatiti, Dipartimento di Scienze Mediche e Chirurgiche , Università di Bologna , Bologna , Italy.,c Programma Dipartimentale Innovazione Terapeutica Epatopatie Croniche Virali (ITEC), Dipartimento Ospedaliero dell'Apparato Digerente , Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola , Bologna , Italy
| | - Maria Cristina Morelli
- d Medicina Interna per il trattamento delle gravi insufficienze d'organo , Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola , Bologna , Italy
| | - Antonio Daniele Pinna
- e Chirurgia Generale e Trapianti , Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola , Bologna , Italy
| | - Silvana Grandi
- a Dipartimento di Psicologia , Università di Bologna , Bologna , Italy
| | - Pietro Andreone
- b Centro di Ricerca per lo Studio delle Epatiti, Dipartimento di Scienze Mediche e Chirurgiche , Università di Bologna , Bologna , Italy.,c Programma Dipartimentale Innovazione Terapeutica Epatopatie Croniche Virali (ITEC), Dipartimento Ospedaliero dell'Apparato Digerente , Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola , Bologna , Italy
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Ponziani FR, Miele L, Tortora A, Furnari M, Bodini G, Pompili M, Gasbarrini A, Giannini EG. Treatment of early stage chronic hepatitis C virus infection. Expert Rev Clin Pharmacol 2018; 11:519-524. [PMID: 29498556 DOI: 10.1080/17512433.2018.1447923] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2023]
Abstract
INTRODUCTION Treatment of Hepatitis C Virus (HCV) with direct acting antivirals (DAAs) is able to achieve the cure of infection in almost the totality of patients, independently of the characteristics of the individual and the virus, using short treatment schedules, and without the need of ribavirin. The high cost of DAAs is the main limiting factor for universal treatment of HCV. However, there is a strong evidence that treatment of infection at the early stage of disease may be the most rewarding approach. Areas covered: This review evaluates the aspects underlying the benefit of treating chronic HCV infection at the early stage of disease. It outlines the considerations that have to be taken into account when planning treatment in patients with HCV and minimal liver disease, assessing the positive reflex of viral eradication on several HCV-associated extra-hepatic conditions such as the risk of lymphoma, insulin-resistance and glycaemic control, and renal function. Lastly, it also covers the improvement of patients' quality of life and the pharmaco-economic aspects associated with early treatment. Expert commentary: Treatment of patients with HCV and minimal liver disease is associated with a beneficial, pleiotropic effect of viral eradication that goes beyond the simplistic consideration of the improvement in liver disease-related outcomes.
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Affiliation(s)
- Francesca Romana Ponziani
- a Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico "A. Gemelli" , Catholic University of Rome , Rome , Italy
| | - Luca Miele
- a Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico "A. Gemelli" , Catholic University of Rome , Rome , Italy
| | - Annalisa Tortora
- a Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico "A. Gemelli" , Catholic University of Rome , Rome , Italy
| | - Manuele Furnari
- b Gastroenterology Unit, Department of Internal Medicine , University of Genoa, IRCCS Ospedale Policlinico San Martino , Genoa , Italy
| | - Giorgia Bodini
- b Gastroenterology Unit, Department of Internal Medicine , University of Genoa, IRCCS Ospedale Policlinico San Martino , Genoa , Italy
| | - Maurizio Pompili
- a Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico "A. Gemelli" , Catholic University of Rome , Rome , Italy
| | - Antonio Gasbarrini
- a Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico "A. Gemelli" , Catholic University of Rome , Rome , Italy
| | - Edoardo Giovanni Giannini
- b Gastroenterology Unit, Department of Internal Medicine , University of Genoa, IRCCS Ospedale Policlinico San Martino , Genoa , Italy
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13
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Mapoure NY, Budzi MN, Eloumou SAFB, Malongue A, Okalla C, Luma HN. Neurological manifestations in chronic hepatitis C patients receiving care in a reference hospital in sub-Saharan Africa: A cross-sectional study. PLoS One 2018; 13:e0192406. [PMID: 29513678 PMCID: PMC5841655 DOI: 10.1371/journal.pone.0192406] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2017] [Accepted: 01/22/2018] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND Chronic hepatitis C infection is a major public health concern, with a high burden in Sub-Saharan Africa. There is growing evidence that chronic hepatitis C virus (HCV) infection causes neurological complications. This study aimed at assessing the prevalence and factors associated with neurological manifestations in chronic hepatitis C patients. METHODS Through a cross-sectional design, a semi-structured questionnaire was used to collect data from consecutive chronic HCV infected patients attending the outpatient gastroenterology unit of the Douala General Hospital (DGH). Data collection was by interview, patient record review (including HCV RNA quantification, HCV genotyping and the assessment of liver fibrosis and necroinflammatory activity), clinical examination complemented by 3 tools; Neuropathic pain diagnostic questionnaire, Brief peripheral neuropathy screen and mini mental state examination score. Data were analysed using Statistical package for social sciences version 20 for windows. RESULTS Of the 121 chronic hepatitis C patients (51.2% males) recruited, 54.5% (95% Confidence interval: 46.3%, 62.8%) had at least one neurological manifestation, with peripheral nervous system manifestations being more common (50.4%). Age ≥ 55 years (Adjusted Odds Ratio: 4.82, 95%CI: 1.02-18.81, p = 0.02), longer duration of illness (AOR: 1.012, 95%CI: 1.00-1.02, p = 0.01) and high viral load (AOR: 3.40, 95% CI: 1.20-9.64, p = 0.02) were significantly associated with neurological manifestations. Peripheral neuropathy was the most common neurological manifestation (49.6%), presenting mainly as sensory neuropathy (47.9%). Age ≥ 55 years (AOR: 6.25, 95%CI: 1.33-29.08, p = 0.02) and longer duration of illness (AOR: 1.01, 1.00-1.02, p = 0.01) were significantly associated with peripheral neuropathy. CONCLUSION Over half of the patients with chronic hepatitis C attending the DGH have a neurological manifestation, mainly presenting as sensory peripheral neuropathy. Routine screening of chronic hepatitis C patients for peripheral neuropathy is therefore necessary, with prime focus on those with older age and longer duration of illness.
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Affiliation(s)
- N. Y. Mapoure
- Department of Clinical Sciences, Faculty of Medicine and Pharmaceutical Sciences, University of Douala, Douala, Cameroon
- Department of Internal Medicine, Douala General Hospital, Douala, Cameroon
| | - M. N. Budzi
- Faculty of Health Sciences, University of Buea, Buea, Cameroon
| | - S. A. F. B. Eloumou
- Department of Clinical Sciences, Faculty of Medicine and Pharmaceutical Sciences, University of Douala, Douala, Cameroon
- Department of Internal Medicine, Douala General Hospital, Douala, Cameroon
| | - A. Malongue
- Department of Internal Medicine, Douala General Hospital, Douala, Cameroon
| | - C. Okalla
- Department of Internal Medicine, Douala General Hospital, Douala, Cameroon
- Department of Biological Sciences, Faculty of Medicine and Pharmaceutical Sciences, University of Douala, Douala, Cameroon
| | - H. N. Luma
- Department of Internal Medicine, Douala General Hospital, Douala, Cameroon
- Department of Internal Medicine, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaounde, Cameroon
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14
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Kumar A, Deep A, Gupta RK, Atam V, Mohindra S. Brain Microstructural Correlates of Cognitive Dysfunction in Clinically and Biochemically Normal Hepatitis C Virus Infection. J Clin Exp Hepatol 2017; 7:198-204. [PMID: 28970706 PMCID: PMC5620352 DOI: 10.1016/j.jceh.2017.03.011] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2016] [Accepted: 03/14/2017] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND/AIMS This study examined correlates of the brain's neurocognitive performance among clinically and biochemically normal adult patient with hepatitis C virus (HCV). We hypothesized that anti-HCV positive individuals would demonstrate structural brain abnormalities and neurocognitive dysfunction as well as the changes in cell component and extracellular space in the white matter regions of brain in asymptomatic HCV infection by using diffusion tensor tractrography (DTT) metrics. METHODS Anti-HCV positive patient (n = 40), and healthy controls (n = 31), fulfilling inclusion criteria (incidentally detected anti-HCV positive) and able to provide informed consent were screened and recruited for the study. All these subjects and controls underwent subjective assessment of their quality of life related symptoms, neuropsychometric tests (NPT) and magnetic resonance imaging. RESULTS The patients were subjected to neuroimaging as well as psychological testing. There was no significant difference in basic laboratory parameters in these two groups. Independent t-test reveals significantly lower neuropsychological functioning as compared to healthy control. A significantly decreased FA values and myoinsitol were observed in HCV subjects on sensory, inferior longitudinal fascicules, and STR fiber bundles as compared to healthy control. Bivariate correlation analysis reveals that neuropsychological scores are significantly positive. CONCLUSION Our result show that HCV positive individuals would demonstrate structural brain abnormalities and neurocognitive dysfunction as well as the changes in cell component and extracellular space in the white matter regions of brain in asymptomatic HCV infection by using DTT metrics.
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Key Words
- BD, block design
- CC, central cortex
- Cho, choline
- DS, digit symbol
- DTT, diffusion tensor tractrography
- FA, fractional anisotrophy
- FCA, figure connection test A
- FCB, figure connection test B
- Gln, glutamine
- Glx, glutamate
- ILF, inferior longitudinal fascicules
- Ins, inositol
- MD, mean diffusivity
- MRI
- NAA, N-acetylaspartate
- OA, object assembly
- PA, picture arrangement
- PC, picture completion
- QOL, quality of life
- SLF, superior longitudinal fascicules
- STR fiber bundles
- STR, superior thalamic radiations
- hepatitis C virus
- myoinsitol
- neuropsychometric tests
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Affiliation(s)
- Ajay Kumar
- Department of Medical Gastroenterology, King George's Medical University, Lucknow 226003, India,Address for correspondence: Ajay Kumar, Assistant Prof, Department of Medical Gastroenterology, K.G. Medical University, Lucknow, UP 226003, India. Tel.: +91 9455519306.Department of Medical Gastroenterology, K.G. Medical UniversityLucknowUP226003India
| | - Amar Deep
- Department of Medical Gastroenterology, King George's Medical University, Lucknow 226003, India,Experimental and Public Health Lab, Department of Zoology, University of Lucknow, 226003, India
| | - Rakesh K. Gupta
- Department of Radiodiagnosis, SGPGIMS, Lucknow 226003, India
| | - Virendra Atam
- Department of Medicine, King George's Medical University, India
| | - Samir Mohindra
- Department of Gastroenterology, SGPGIMS, Lucknow, UP, India
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15
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Dirks M, Pflugrad H, Haag K, Tillmann HL, Wedemeyer H, Arvanitis D, Hecker H, Tountopoulou A, Goldbecker A, Worthmann H, Weissenborn K. Persistent neuropsychiatric impairment in HCV patients despite clearance of the virus?! J Viral Hepat 2017; 24:541-550. [PMID: 28117537 DOI: 10.1111/jvh.12674] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2016] [Accepted: 12/14/2016] [Indexed: 12/30/2022]
Abstract
One of the most disabling symptoms of hepatitis C virus (HCV) infection is chronic fatigue. While this is accepted for HCV polymerase chain reaction (PCR)-positive patients, a relationship between HCV infection and chronic fatigue is questioned after successful virus eradication. As fatigue is a subjective criterion, we aimed to evaluate in addition mood alterations and cognitive function in HCV-exposed patients with only mild liver disease and to assess a) possible interrelationships between these factors and health-related quality of life and b) the impact of viremia and former interferon treatment. One hundred and fifty-nine anti-HCV-positive individuals without advanced liver disease answered health-related quality of life (HRQoL), fatigue and depression questionnaires and underwent a battery of attention and memory tests. Accompanying diseases which could distort the results of the study such as HIV co-infection or drug addiction were exclusion criteria. The patients were subdivided into four groups according to their viremia status and interferon treatment history. Patients' data were evaluated with respect to norms given in the respective test manuals and in addition compared to those of 33 age-matched healthy controls. Eighty-five per cent of the patients had chronic fatigue, 50-60% mild depression or anxiety, 45% memory deficits and 30% attention deficits, irrespective of their HCV viremia status or treatment history. HRQoL correlated negatively with chronic fatigue (P<.001), while cognitive deficits-especially memory function-were independent from fatigue and depression. HCV infection may cause long-standing cerebral dysfunction that significantly impairs HRQoL and may even persist after clearance of the virus.
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Affiliation(s)
- M Dirks
- Department of Neurology, Hannover Medical School, Hannover, Germany
| | - H Pflugrad
- Department of Neurology, Hannover Medical School, Hannover, Germany
| | - K Haag
- Department of Neurology, Hannover Medical School, Hannover, Germany
| | - H L Tillmann
- Division of Gastroenterology, Hepatology & Nutrition, East Carolina University, Greenville, NC, USA
| | - H Wedemeyer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - D Arvanitis
- Department of Neurology, Hannover Medical School, Hannover, Germany
| | - H Hecker
- Department of Biometrics, Hannover Medical School, Hannover, Germany
| | - A Tountopoulou
- Department of Neurology, Hannover Medical School, Hannover, Germany
| | - A Goldbecker
- Department of Neurology, Hannover Medical School, Hannover, Germany
| | - H Worthmann
- Department of Neurology, Hannover Medical School, Hannover, Germany
| | - K Weissenborn
- Department of Neurology, Hannover Medical School, Hannover, Germany
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16
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Evon DM, Golin CE, Ruffin R, Fried MW. Development and Pilot-Testing of a Cognitive Behavioral Coping Skills Group Intervention for Patients with Chronic Hepatitis C. Contemp Clin Trials Commun 2017; 6:85-96. [PMID: 29082334 PMCID: PMC5654628 DOI: 10.1016/j.conctc.2017.03.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2016] [Revised: 03/08/2017] [Accepted: 03/18/2017] [Indexed: 02/08/2023] Open
Abstract
Psychosocial interventions for patients with chronic hepatitis C viral (HCV) infection are needed to attenuate the impact of extrahepatic symptoms, comorbid conditions, and treatment side effects on HCV health outcomes. We adapted empirically-supported interventions for similar patient populations to develop a Cognitive Behavioral Coping Skills group intervention for HCV patients (CBCS-HCV) undergoing treatment. The objectives of this paper are to describe the research activities associated with CBCS-HCV development and pilot testing, including: (1) formative work leading to intervention development; (2) preliminary study protocol; and (3) pilot feasibility testing of the intervention and study design. Formative work included a literature review, qualitative interviews, and adaption, development, and review of study materials. A preliminary study protocol is described. We evaluate the feasibility of conducting a randomized controlled trial (RCT) of the CBCS-HCV with 12 study participants in Wave 1 testing to examine: (a) feasibility of intervention delivery; (b) patient acceptability; (c) recruitment, enrollment, retention; (d) feasibility of conducting a RCT; (d) therapist protocol fidelity; and (e) feasibility of data collection. Numerous lessons were learned. We found very high rates of data collection, participant attendance, engagement, retention and acceptability, and therapist protocol fidelity. We conclude that many aspects of the CBCS-HCV intervention and study protocol were highly feasible. The greatest challenge during this Wave 1 pilot study was efficiency of participant enrollment due to changes in standard of care treatment. These findings informed two additional waves of pilot testing to examine effect sizes and potential improvements in clinical outcomes, with results forthcoming.
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Affiliation(s)
- Donna M. Evon
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, USA
| | - Carol E. Golin
- Department of Medicine, University of North Carolina, Chapel Hill, NC, USA
- Department of Health Behavior, University of North Carolina, Chapel Hill, NC, USA
| | - Rachel Ruffin
- Durham Veterans Affairs Medical Center, Durham, NC, USA
| | - Michael W. Fried
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, USA
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17
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Kharabian Masouleh S, Herzig S, Klose L, Roggenhofer E, Tenckhoff H, Kaiser T, Thöne-Otto A, Wiese M, Berg T, Schroeter ML, Margulies DS, Villringer A. Functional connectivity alterations in patients with chronic hepatitis C virus infection: A multimodal MRI study. J Viral Hepat 2017; 24:216-225. [PMID: 27813284 DOI: 10.1111/jvh.12634] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2016] [Accepted: 10/05/2016] [Indexed: 12/13/2022]
Abstract
Chronic hepatitis C virus (HCV) infection is associated with fatigue and depression. Cognitive impairments are also reported in a smaller number of HCV-positive patients. Recent studies linked HCV to low-grade inflammation in brain. Here, we test the hypothesis that chronic HCV is associated with 3T-neuroimaging-derived grey matter volume (GMV) and functional connectivity alterations in a sample of chronic HCV (1b), without severe liver disease. Regional GMV and resting-state fMRI-derived eigenvector centrality (EC) were compared between 19 HCV-positive patients and 23 healthy controls (all females, 50-69 and 52-64 years, respectively), controlling for white matter hyperintensities and age. Standard tests were used to assess fatigue, depression and cognitive performance. Also, liver fibrosis stage and viral load were quantified among patients. In comparison with controls, HCV-positive patients had higher scores in fatigue and depression, and worse alertness scores. The groups performed similarly in other cognitive domains. We report higher EC in a cluster in the right anterior superior parietal lobule in patients, while no differences are found in GMV. Post hoc functional connectivity analysis showed increased connectivity of this cluster with primary and secondary somatosensory cortex, and temporal and occipital lobes in patients. Higher mean EC in the superior parietal cluster, adjusted for mean framewise displacement, was associated with better memory and attention performance, but not with fatigue, depression, viral load or level of liver fibrosis, among patients. These results suggest a compensatory mechanism in chronic hepatitis C and explain equivocal results in the literature about cognitive deficits in infected persons. Further studies should define the relation of these connectivity changes to the brain's inflammatory activity.
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Affiliation(s)
- S Kharabian Masouleh
- Department of Neurology, Max Planck Institute for Cognitive and Brain Sciences, Leipzig, Germany
| | - S Herzig
- Clinic for Cognitive Neurology, University of Leipzig, Leipzig, Germany
| | - L Klose
- Clinic for Cognitive Neurology, University of Leipzig, Leipzig, Germany
| | - E Roggenhofer
- Department of Neurology, Max Planck Institute for Cognitive and Brain Sciences, Leipzig, Germany.,LREN, Department for Clinical Neurosciences, CHUV, University of Lausanne, Lausanne, Switzerland
| | - H Tenckhoff
- Section of Hepatology, Department of Gastroenterology and Rheumatology, University Hospital, Leipzig, Germany
| | - T Kaiser
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig, Germany
| | - A Thöne-Otto
- Clinic for Cognitive Neurology, University of Leipzig, Leipzig, Germany
| | - M Wiese
- Section of Hepatology, Department of Gastroenterology and Rheumatology, University Hospital, Leipzig, Germany
| | - T Berg
- Section of Hepatology, Department of Gastroenterology and Rheumatology, University Hospital, Leipzig, Germany
| | - M L Schroeter
- Department of Neurology, Max Planck Institute for Cognitive and Brain Sciences, Leipzig, Germany.,Clinic for Cognitive Neurology, University of Leipzig, Leipzig, Germany
| | - D S Margulies
- Max Planck Research Group for Neuroanatomy and Connectivity, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
| | - A Villringer
- Department of Neurology, Max Planck Institute for Cognitive and Brain Sciences, Leipzig, Germany.,Clinic for Cognitive Neurology, University of Leipzig, Leipzig, Germany
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18
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Yarlott L, Heald E, Forton D. Hepatitis C virus infection, and neurological and psychiatric disorders - A review. J Adv Res 2016; 8:139-148. [PMID: 28149649 PMCID: PMC5272938 DOI: 10.1016/j.jare.2016.09.005] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2016] [Revised: 09/09/2016] [Accepted: 09/09/2016] [Indexed: 02/06/2023] Open
Abstract
An association between hepatitis C virus infection and neuropsychiatric symptoms has been proposed for some years. A variety of studies have been undertaken to assess the nature and severity of these symptoms, which range from fatigue and depression to defects in attention and verbal reasoning. There is evidence of mild neurocognitive impairment in some patients with HCV infection, which is not fully attributable to liver dysfunction or psychosocial factors. Further evidence of a biological cerebral effect has arisen from studies using magnetic resonance spectroscopy; metabolic abnormalities correlate with cognitive dysfunction and resemble the patterns of neuroinflammation that have been described in HIV infection. Recent research has suggested that, in common with HIV infection, HCV may cross the blood brain barrier leading to neuroinflammation. Brain microvascular endothelial cells, astrocytes and microglia may be minor replication sites for HCV. Importantly, patient reported outcomes improve following successful antiviral therapy. Further research is required to elucidate the molecular basis for HCV entry and replication in the brain, and to clarify implications and recommendations for treatment.
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Affiliation(s)
- Lydia Yarlott
- Department of Gastroenterology and Hepatology, St George's University Hospitals NHS Foundation Trust, Blackshaw Rd, London SW17 0QT, United Kingdom
| | - Eleanor Heald
- Department of Gastroenterology and Hepatology, St George's University Hospitals NHS Foundation Trust, Blackshaw Rd, London SW17 0QT, United Kingdom
| | - Daniel Forton
- Department of Gastroenterology and Hepatology, St George's University Hospitals NHS Foundation Trust, Blackshaw Rd, London SW17 0QT, United Kingdom; St George's, University of London, Cranmer Terrace, London SW17 0RE, United Kingdom
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19
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Barboza KC, Salinas LM, Sahebjam F, Jesudian AB, Weisberg IL, Sigal SH. Impact of depressive symptoms and hepatic encephalopathy on health-related quality of life in cirrhotic hepatitis C patients. Metab Brain Dis 2016; 31:869-80. [PMID: 27032930 DOI: 10.1007/s11011-016-9817-y] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2015] [Accepted: 03/01/2016] [Indexed: 02/06/2023]
Abstract
Depression, common in chronic medical conditions, and hepatic encephalopathy (HE), a reversible neuropsychiatric syndrome due to liver dysfunction, are associated with impaired health-related quality of life (HRQOL) in cirrhosis and hepatitis C (HCV). This study investigated the impact of depression and HE on HRQOL in cirrhotic patients with HCV. A convenience sample of 43 ambulatory patients, with varying degrees of cirrhosis secondary to HCV, was prospectively enrolled in this study. Participants were assessed for any current depressive, fatigue, and daytime sleepiness symptoms and underwent a psychometric evaluation to determine the presence of HE symptoms. Participants reported current HRQOL on general health and liver disease-specific questionnaires. Diagnosis and current health status were confirmed via medical records. The associations between disease severity, depressive symptoms, HE, fatigue, and daytime sleepiness were measured. Predictors of HRQOL in this sample were determined. Depressive symptoms (70 %) and HE (77 %) were highly prevalent in this sample, with 58 % actively experiencing both conditions at the time of study participation. A significant positive association was found between depressive symptoms and HE severity (P = .05). Depressive symptoms were significantly associated with fatigue (P < .001), daytime sleepiness (P < .001), general HRQOL (P < .001), and disease-specific HRQOL (P < .001). HE was significantly associated with fatigue (P = .02), general HRQOL (P < .001), and disease-specific HRQOL (P < .001). Depressive symptoms and HE were significant predictors of reduced HRQOL (P < .001), with depressive symptoms alone accounting for 58.8 % of the variance. Depressive symptoms and HE accounted for 68.0 % of the variance. Findings suggest a possible pathophysiological link between depression and HE in cirrhosis, and potentially a wider-reaching benefit of treating minimal and overt HE than previously appreciated.
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Affiliation(s)
- Katherine C Barboza
- Department of Medicine, New York University Langone Medical Center, New York City, NY, USA.
| | - Lilian M Salinas
- Division of Gastroenterology, Department of Medicine, New York University Langone Medical Center, New York City, NY, USA
| | - Farhad Sahebjam
- Division of Gastroenterology, Department of Medicine, New York University Langone Medical Center, New York City, NY, USA
| | - Arun B Jesudian
- Center for Liver Disease and Transplantation, New York Presbyterian Weill Cornell Medical Center, New York, NY, USA
| | - Ilan L Weisberg
- Division of Gastroenterology, Department of Medicine, New York University Langone Medical Center, New York City, New York, USA
| | - Samuel H Sigal
- Division of Gastroenterology, Department of Medicine, New York University Langone Medical Center, New York City, NY, USA
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20
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Ibrahim I, Salah H, El Sayed H, Mansour H, Eissa A, Wood J, Fathi W, Tobar S, Gur RC, Gur RE, Dickerson F, Yolken RH, El Bahaey W, Nimgaonkar V. Hepatitis C virus antibody titers associated with cognitive dysfunction in an asymptomatic community-based sample. J Clin Exp Neuropsychol 2016; 38:861-8. [PMID: 27269819 DOI: 10.1080/13803395.2016.1168780] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is associated with cognitive dysfunction in clinic-based studies. The risk could be attributed to factors such as antiviral medications, substance abuse, or coincidental infection. AIM The aim was to evaluate cognitive function in relation to HCV antibody titers in a community-based sample of asymptomatic individuals at low risk for substance abuse. METHOD Adults were ascertained from a community in Mansoura, Egypt, where HCV is endemic (n = 258). Cognitive performance was evaluated using the Arabic version of the Penn Computerized Neurocognitive Battery. Substance abuse and psychopathology were also assessed. Antibodies to HCV and Toxoplasma gondii (TOX), a common protozoan that can affect cognition, were estimated using serological IgG assays. RESULTS The prevalence of HCV and TOX infection was 17.6% and 52.9%, respectively. HCV antibody titers were significantly associated with worse function in four cognitive tests for accuracy and three tests for speed, after adjusting for covariates (p < .05, beta coefficients, 2.1-3.2). TOX antibody titers were associated with impaired accuracy in one test. CONCLUSIONS The association between HCV antibody titers and cognitive impairment is not mediated by antiviral treatment or substance abuse in this sample. Whether HCV has a causal role in the cognitive dysfunction should be investigated.
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Affiliation(s)
- Ibtihal Ibrahim
- b Department of Psychiatry , Mansoura University School of Medicine , Mansoura , Egypt
| | - Hala Salah
- b Department of Psychiatry , Mansoura University School of Medicine , Mansoura , Egypt
| | - Hanan El Sayed
- b Department of Psychiatry , Mansoura University School of Medicine , Mansoura , Egypt
| | - Hader Mansour
- a Department of Psychiatry , University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic , Pittsburgh , PA , USA.,b Department of Psychiatry , Mansoura University School of Medicine , Mansoura , Egypt
| | - Ahmed Eissa
- b Department of Psychiatry , Mansoura University School of Medicine , Mansoura , Egypt
| | - Joel Wood
- a Department of Psychiatry , University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic , Pittsburgh , PA , USA
| | - Warda Fathi
- b Department of Psychiatry , Mansoura University School of Medicine , Mansoura , Egypt
| | - Salwa Tobar
- b Department of Psychiatry , Mansoura University School of Medicine , Mansoura , Egypt
| | - Ruben C Gur
- d Neuropsychiatry Section, Department of Psychiatry , University of Pennsylvania Perelman School of Medicine , Philadelphia , PA , USA
| | - Raquel E Gur
- d Neuropsychiatry Section, Department of Psychiatry , University of Pennsylvania Perelman School of Medicine , Philadelphia , PA , USA
| | - Faith Dickerson
- e Department of Pediatrics , Johns Hopkins School of Medicine , Baltimore , MD , USA
| | - Robert H Yolken
- f Department of Pediatrics , Stanley Division of Developmental Neurovirology , Baltimore , MD , USA
| | - Wafaa El Bahaey
- b Department of Psychiatry , Mansoura University School of Medicine , Mansoura , Egypt
| | - Vishwajit Nimgaonkar
- a Department of Psychiatry , University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic , Pittsburgh , PA , USA.,c Department of Human Genetics , Graduate School of Public Health, University of Pittsburgh , Pittsburgh , PA , USA
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21
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Fialho R, Pereira M, Bucur M, Fisher M, Whale R, Rusted J. Cognitive impairment in HIV and HCV co-infected patients: a systematic review and meta-analysis. AIDS Care 2016. [DOI: 10.1080/09540121.2016.1191614] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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22
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Cacoub P, Comarmond C, Domont F, Savey L, Desbois AC, Saadoun D. Extrahepatic manifestations of chronic hepatitis C virus infection. Ther Adv Infect Dis 2016; 3:3-14. [PMID: 26862398 DOI: 10.1177/2049936115585942] [Citation(s) in RCA: 115] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
During hepatitis C virus (HCV) chronic infection, extrahepatic manifestations are frequent and polymorphous. This article reports on a large cohort of patients with HCV-related autoimmune or lymphoproliferative disorders, from mixed cryoglobulinemia vasculitis to frank lymphomas. The relationship between HCV infection and such immune-related diseases has been formally demonstrated by epidemiological, clinical, immunological and pathological data, and results of therapeutic trials. More recently, other nonliver-related HCV disorders have been reported, including cardiovascular (i.e. stroke, ischemic heart disease), renal, metabolic and central nervous system diseases. For these manifestations, most evidence comes from large epidemiological studies; there is a need for mechanistic studies and therapeutic trials for confirmation. Beyond the risk of developing liver complications, that is, cirrhosis and liver cancer, patients with HCV infection have an increased risk of morbidity and mortality related to nonliver diseases. HCV chronic infection should be analyzed as a systemic disease in which extrahepatic consequences increase the weight of its pathological burden. The need for effective viral eradication measures is underlined.
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Affiliation(s)
- Patrice Cacoub
- Sorbonne Universités, UPMC Univ Paris 06, and Inflammation Immunopathology Biotherapy Department (DHU i2B), Paris, France
| | | | | | - Léa Savey
- Sorbonne Universités, UPMC Univ Paris 06, and Inflammation Immunopathology Biotherapy Department (DHU i2B), Paris, France
| | | | - David Saadoun
- Sorbonne Universités, UPMC Univ Paris 06, and Inflammation Immunopathology Biotherapy Department (DHU i2B), Paris, France
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23
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Abstract
Patients with chronic hepatitis C virus (HCV) infection frequently present with extrahepatic manifestations covering a large spectrum, involving different organ systems leading to the concept of systemic HCV infection. These manifestations include autoimmune phenomena and frank autoimmune and/or rheumatic diseases and may dominate the course of chronic HCV infection. Chronic HCV infection causes liver inflammation affecting the development of hepatic diseases. HCV is also a lymphotropic virus that triggers B cells and promotes favorable conditions for B lymphocyte proliferation, including mixed cryoglobulinemia (MC) and MC vasculitis, which is the most prominent extrahepatic manifestation of chronic HCV infection. HCV may also promote a low-grade chronic systemic inflammation that may affect the development of some extrahepatic manifestations, particularly cardiovascular and cerebral vascular diseases. Recognition of extrahepatic symptoms of HCV infection could facilitate early diagnosis and treatment. The development of direct-acting antiviral agents (DDAs) has revolutionized HCV treatment. DDAs, as well as new B-cell-depleting or B-cell-modulating monoclonal antibodies, will expand the panorama of treatment options for HCV-related extrahepatic manifestations including cryoglobulinemic vasculitis. In this context, a proactive, integrated approach to HCV therapy should maximize the benefits of HCV therapy, even when liver disease is mild.
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Affiliation(s)
- E Rosenthal
- Service de Médecine Interne, Hôpital de l'Archet, CHU de Nice, Nice; Université de Nice-Sophia Antipolis, Nice, France COREVIH PACA EST, CHU de Nice, France
| | - P Cacoub
- Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France INSERM, UMR_S 959, Paris, France CNRS, FRE3632, Paris, France AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
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Fialho R, Pereira M, Bucur M, Fisher M, Whale R, Rusted J. Cognitive impairment in HIV and HCV co-infected patients: a systematic review and meta-analysis. AIDS Care 2015. [PMID: 26542344 DOI: 10.1080/09540121.2015.1108385] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Cognitive impairment has been well documented in HIV and hepatitis C virus (HCV) mono-infections. However, in the context of HIV/HCV co-infection the research is more limited. The aim of this systematic review was to describe the characteristics of cognitive impairment in HIV/HCV co-infection and to examine the differences in cognitive performance between HIV/HCV and HIV and HCV mono-infected patients. Of the 437 records initially screened, 24 papers met the inclusion criteria and were included in the systematic review. Four studies were included in the meta-analysis. Most studies indicated that HIV/HCV co-infected patients had a higher level of cognitive impairment than HIV mono-infected patients. Meta-analysis indicated, however, that HIV mono-infected patients had a significantly higher global deficit score than co-infected patients. The results also indicated that co-infected patients were more likely to be impaired in information processing speed than HIV mono-infected patients. These findings can be challenged by biasing factors such as the small number of studies, heterogeneity of the samples, and a large diversity of methodological procedures. Future research with consistent and comprehensive neuropsychological batteries and covering a greater diversity of risk factors is needed, in order to clarify the effects of both viruses on cognitive function and the mechanisms that underlie these effects. Because cognitive impairments may pose significant challenges to medication adherence, quality of life and overall functioning, such knowledge may have important implications to the planning and implementation of effective interventions aimed at optimising the clinical management of these infections.
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Affiliation(s)
- Renata Fialho
- a School of Psychology, University of Sussex , Brighton , UK.,b Sussex Partnership NHS Foundation Trust , Brighton , UK
| | - Marco Pereira
- c Faculty of Psychology and Educational Sciences , University of Coimbra , Coimbra , Portugal
| | - Mihaela Bucur
- b Sussex Partnership NHS Foundation Trust , Brighton , UK
| | - Martin Fisher
- d Elton John Centre , Brighton and Sussex University Hospitals NHS Trust , Brighton , UK.,e Brighton and Sussex Medical School , Brighton , UK
| | - Richard Whale
- b Sussex Partnership NHS Foundation Trust , Brighton , UK.,e Brighton and Sussex Medical School , Brighton , UK
| | - Jennifer Rusted
- a School of Psychology, University of Sussex , Brighton , UK
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Abu Faddan NH, Shehata GA, Abd Elhafeez HA, Mohamed AO, Hassan HS, Abd El Sameea F. Cognitive function and endogenous cytokine levels in children with chronic hepatitis C. J Viral Hepat 2015; 22:665-70. [PMID: 25496114 DOI: 10.1111/jvh.12373] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2014] [Accepted: 10/29/2014] [Indexed: 12/23/2022]
Abstract
Little is known about how hepatitis C (HCV) infection affects cognitive function in children. The aim of the study was to assess the impact of HCV infection on cognitive function of children with normal liver functions and their relationships to endogenous IFN-α, IL-6 and TNF-α. IFN-α, IL-6 and TNF-α were measured and the Arabic version of the Stanford-Binet test used to assess cognitive functions in 35 children with HCV infection and 23 controls. Serum levels of IL-6 and IFN-α were significantly higher in patients compared to controls. There was a significant effect on vocabulary, comprehension, and abstract visual reasoning, quantitative reasoning and bead memory tests, as well as total short-term memory and intelligence quotient in patients compared to controls. There was a significant positive correlation between IFN-α and IL-6. Also there were significant negative correlations between IFN-α and Abstract visual reasoning test, Quantitative reasoning test, Bead memory test, Total short-term memory and Intelligence quotient; and between IL-6 and Abstract visual reasoning test, Quantitative reasoning test and Intelligence quotient. There was no significant correlation between TNF-α and any of the cognitive functions. Cytokine levels were not related to demographic characteristics of the patients or viral load (PCR). Children with chronic hepatitis C infection in its early stages showed signs of cognitive impairment, with the memory tasks being mostly affected. There was a significant correlation between endogenous cytokines and cognitive impairment in these children. Further studies are needed to define the effect of successful antiviral treatment.
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Affiliation(s)
- N H Abu Faddan
- Department of Pediatrics, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - G A Shehata
- Department of Neurology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - H A Abd Elhafeez
- Department of Clinical Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - A O Mohamed
- Department of Biochemistry, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - H S Hassan
- Department of Psychology, Faculty of Art, Assiut University, Assiut, Egypt
| | - F Abd El Sameea
- Department of Psychology, Faculty of Art, Assiut University, Assiut, Egypt
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Lam V, Albrecht MA, Takechi R, Heidari-Nejad S, Foster JK, Mamo JCL. Neuropsychological performance is positively associated with plasma albumin in healthy adults. Neuropsychobiology 2015; 69:31-8. [PMID: 24458291 DOI: 10.1159/000356967] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2013] [Accepted: 11/02/2013] [Indexed: 11/19/2022]
Abstract
BACKGROUND Albumin serves a range of physiological functions that are vital to overall brain and cognitive health. Indeed, associations between cognitive performance and albumin have been demonstrated in individuals with chronic liver or kidney disease and in patients with a high urinary excretion of albumin. However, an association of plasma albumin with cognitive performance has not been reported in otherwise healthy participants with clinically acceptable plasma albumin concentrations. METHOD This study utilized a wide-ranging neuropsychological test battery to investigate the relationship between cognitive performance and plasma albumin homeostasis in 222 healthy participants (143 females) between the ages of 43 and 84 years (mean 65 years). RESULTS Albumin both with and without the covariates of age, sex and acute-phase proteins was positively associated with enhanced performance on a range of neuropsychological domains including perceptual speed, Stroop and verbal ability. Albumin manifested generally positive but less robust associations with secondary and primary memory. CONCLUSION The results indicate that there is a positive association between albumin and cognitive performance in physiologically healthy participants free of chronic renal or liver disease.
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Affiliation(s)
- Virginie Lam
- School of Public Health, Curtin University, Perth, W.A., Australia
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Bassiony MM, Yousef A, Raya Y, El-Shabrawi A, Fouad E, El-Shafeey M. Cognitive impairment in relation to depression, anxiety and virological response in hepatitis C patients in Egypt. Int J Psychiatry Clin Pract 2015; 19:208-15. [PMID: 26099337 DOI: 10.3109/13651501.2015.1064964] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
OBJECTIVE Cognitive impairment commonly occurs in hepatitis C virus (HCV) patients. The objective of this study was to estimate the prevalence and sociodemographic and clinical correlates of cognitive impairment in HCV patients before and after 12 weeks of interferon treatment in comparison with a control group. METHODS Hundred and sixteen consecutive HCV patients were included in the study and divided into treated and untreated groups. All patients were assessed using sociodemographic and clinical questionnaire, Montreal Cognitive Assessment Scale (MOCA) and Hospital Anxiety and Depression Scale (HADS) before and after 12 weeks of treatment or observation. RESULTS Thirty-eight percent of treated patients showed cognitive impairment at baseline, which increased to 69% after 12 weeks of interferon treatment. This cognitive impairment was reflected in the total MOCA score and in visuo-constructional skills, attention, concentration, working memory, language, and short-term memory, which was not shown by untreated group after 12 weeks of observation. Cognitive impairment was associated with low education, but not with depression, anxiety, or virological response. CONCLUSIONS Cognitive impairment is common in HCV patients and increases significantly after interferon treatment. It is not related to depression or anxiety in HCV patients. Future research should focus on prevention, treatment and outcome of cognitive impairment in HCV patients, particularly those receiving interferon therapy.
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Affiliation(s)
- M M Bassiony
- a Department of Psychiatry , Faculty of Medicine, Zagazig University , Egypt
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Soriano V, Labarga P, Fernandez-Montero JV, de Mendoza C, Esposito I, Benítez-Gutiérrez L, Barreiro P. Hepatitis C cure with antiviral therapy – benefits beyond the liver. Antivir Ther 2015; 21:1-8. [DOI: 10.3851/imp2975] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/21/2015] [Indexed: 02/07/2023]
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Cacoub P, Gragnani L, Comarmond C, Zignego AL. Extrahepatic manifestations of chronic hepatitis C virus infection. Dig Liver Dis 2014; 46 Suppl 5:S165-73. [PMID: 25458776 DOI: 10.1016/j.dld.2014.10.005] [Citation(s) in RCA: 190] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2014] [Accepted: 10/03/2014] [Indexed: 02/09/2023]
Abstract
Hepatitis C virus (HCV) infected patients are known to be at risk of developing liver complications i.e. cirrhosis and liver cancer. However, the risks of morbidity and mortality are underestimated because they do not take into account non-liver consequences of chronic hepatitis C virus infection. Numerous extrahepatic manifestations have been reported in up to 74% of patients, from perceived to disabling conditions. The majority of data concern hepatitis C virus-related autoimmune and/or lymphoproliferative disorders, from mixed cryoglobulinaemia vasculitis to frank lymphomas. More recently, other hepatitis C virus-associated disorders have been reported including cardiovascular, renal, metabolic, and central nervous system diseases. This review aims to outline most of the extrahepatic manifestations that are currently being investigated, including some of autoimmune and/or lymphoproliferative nature, and others in which the role of immune mechanisms appears less clear. Beyond the liver, hepatitis C virus chronic infection should be analyzed as a multifaceted systemic disease leading to heavy direct and indirect costs. The accurate consideration of extrahepatic consequences of such a systemic infection significantly increases the weight of its pathological burden. The need for effective viral eradication measures is underlined.
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Affiliation(s)
- Patrice Cacoub
- Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR_S 959, Paris, France; CNRS, FRE3632, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France.
| | - Laura Gragnani
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Cloe Comarmond
- Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR_S 959, Paris, France; CNRS, FRE3632, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
| | - Anna Linda Zignego
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
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Morais-de-Jesus M, Daltro-Oliveira R, Pettersen KM, Dantas-Duarte A, Amaral LDD, Cavalcanti-Ribeiro P, Santos CT, Schinoni MI, Netto LR, Araújo-de-Freitas L, Paraná R, Miranda-Scippa Â, Koenen KC, Quarantini LC. Hepatitis C virus infection as a traumatic experience. PLoS One 2014; 9:e110529. [PMID: 25340574 PMCID: PMC4207714 DOI: 10.1371/journal.pone.0110529] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2014] [Accepted: 09/23/2014] [Indexed: 01/08/2023] Open
Abstract
OBJECTIVE The purpose of this study was to evaluate whether individuals consider their HCV infection to be a potentially traumatic experience. Additionally, we investigated its association with Post-Traumatic Stress Disorder (PTSD) and the impact of PTSD diagnosis on health-related quality of life (HRQoL) in HCV infected subjects. METHODS We conducted a cross-sectional survey of 127 HCV-infected outpatients recruited at a University Hospital in Salvador, Brazil. All subjects answered an orally-administered questionnaire to gather clinical and socio-demographic data. We investigated traumatic experiences and the subject's perception of the disease using the Trauma History Questionnaire. PTSD and other psychiatric diagnoses were assessed through the Mini International Neuropsychiatric Interview-Brazilian Version 5.0.0 (M.I.N.I. PLUS). HRQoL was assessed using Short-Form 36 (SF-36). RESULTS Approximately 38.6% of the patients considered hepatitis C to be a traumatic experience. Of these, 60.7% had a PTSD diagnosis. PTSD was associated with significant impairment in quality of life for individuals in seven SF-36 domains as shown bymultivariate analysis: Role-Physical (β: -24.85; 95% CI: -42.08; -7.61), Bodily Pain (β: -19.36; 95% CI: -31.28; -7.45), General Health (β: -20.79; 95% CI: -29.65; -11.92), Vitality (β: -11.92; 95% CI: -20.74; -3.1), Social Functioning (β: -34.73; 95% CI: -46.79; -22.68), Role-Emotional (β: -26.07; 95% CI: -44.61; -7.53), Mental Health (β: -17.46; 95% CI: -24.38; -10.54). CONCLUSION HCV is frequently a traumatic experience and it is strongly associated with PTSD diagnosis. PTSD significantly impaired HRQoL.
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Affiliation(s)
- Mychelle Morais-de-Jesus
- Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Universidade Federal da Bahia, Salvador, BA, Brazil
| | | | - Karine Miranda Pettersen
- Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Universidade Federal da Bahia, Salvador, BA, Brazil
| | - Adriana Dantas-Duarte
- Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Universidade Federal da Bahia, Salvador, BA, Brazil
| | | | - Patrícia Cavalcanti-Ribeiro
- Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Universidade Federal da Bahia, Salvador, BA, Brazil
| | - Carlos Teles Santos
- Departamento de Ciências Exatas, Universidade Estadual de Feira de Santana, Feira de Santana, BA, Brazil
- Instituto de Saúde Coletiva, Universidade Federal da Bahia, Salvador, BA, Brazil
| | - Maria Isabel Schinoni
- Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Universidade Federal da Bahia, Salvador, BA, Brazil
| | - Liana R. Netto
- Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Universidade Federal da Bahia, Salvador, BA, Brazil
| | - Lucas Araújo-de-Freitas
- Hospital Universitário e Departamento de Neurociências e Saúde Mental da Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, BA, Brazil
| | - Raymundo Paraná
- Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Universidade Federal da Bahia, Salvador, BA, Brazil
- Faculdade de Medicina da Universidade Federal da Bahia, Salvador, BA, Brazil
| | - Ângela Miranda-Scippa
- Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Universidade Federal da Bahia, Salvador, BA, Brazil
- Hospital Universitário e Departamento de Neurociências e Saúde Mental da Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, BA, Brazil
| | - Karestan C. Koenen
- Department of Epidemiology, Mailman School of Public Health - Columbia University, New York, New York, United States of America
| | - Lucas C. Quarantini
- Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Universidade Federal da Bahia, Salvador, BA, Brazil
- Hospital Universitário e Departamento de Neurociências e Saúde Mental da Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, BA, Brazil
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Colagreco JP, Bailey DE, Fitzpatrick JJ, Musil CM, Afdhal NH, Lai M. Watchful waiting: role of disease progression on uncertainty and depressive symptoms in patients with chronic hepatitis C. J Viral Hepat 2014; 21:727-33. [PMID: 25280230 PMCID: PMC4185928 DOI: 10.1111/jvh.12207] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2013] [Accepted: 09/11/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS New therapies for HCV are rapidly emerging and providers are advising select patients to defer treatment and elect 'watchful waiting'. During the watchful waiting period, patients have been shown to have high rates of illness uncertainty and depression. We sought to answer the question of whether reassuring histological data (showing minimal fibrosis or no fibrosis progression over time) is associated with less illness uncertainty and depressive symptoms. METHODS This was a single-centre outpatient prospective cohort study to determine whether stage of fibrosis, fibrosis progression and reasons for treatment deferral were related to illness uncertainty and depressive symptoms in patients following watchful waiting. RESULTS Illness uncertainty was significantly related to depressive symptoms (r = 0.49, P < 0.01). More than half of the participants (54%) had moderate levels of uncertainty. About 40% of the participants were at risk for clinical depression (21.7% at mild to moderate risk and 18.5% at high risk). Treatment naïve subjects had lower mean scores on both the CES-D (depressive symptoms measure) and the MUIS-A (illness uncertainty measure) total score, MUIS-A Ambiguity subscale and MUIS-A Inconsistency subscale than subjects who failed treatment or were interferon intolerant or ineligible. Surprisingly, liver fibrosis stage and progression were not significantly associated with overall illness uncertainty or depressive symptoms. CONCLUSION Patients with chronic hepatitis C on watchful waiting are at high risk for significant illness uncertainty and depressive symptoms. Reassuring histological data does not seem to correlate with less uncertainty or depressive symptoms.
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Affiliation(s)
| | | | | | - Carol M. Musil
- Frances Payne Bolton School of Nursing, Case Western Reserve University
| | | | - Michelle Lai
- Harvard University, Beth Israel Deaconess Medical Center
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Madsen LW, Fabricius T, Hjerrild S, Hansen TM, Mössner BK, Birkemose I, Skamling M, Christensen PB. Depressive symptoms are frequent among drug users, but not associated with hepatitis C infection. ACTA ACUST UNITED AC 2014; 46:566-72. [PMID: 24934987 DOI: 10.3109/00365548.2014.918274] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
AIM To compare the prevalence and severity of depressive symptoms among drug users with and without hepatitis C virus (HCV) infection. METHODS This was a cross-sectional survey study carried out at the 2 major drug treatment centres on the island of Funen, Denmark. Participants were drug users presenting to the 2 treatment centres. Individuals with chronic hepatitis B virus or HIV infection were excluded. Participants completed the Major Depression Inventory (MDI) questionnaire when presenting at the centres. Patients with MDI scores indicating severe depression (total MDI score ≥ 35) were referred for treatment evaluation. Hepatitis C status was classified by the presence of anti-HCV as a marker of HCV exposure and HCV-RNA as a marker of ongoing infection. RESULTS Two hundred and sixty-eight patients were included, of whom 235 (88%) had complete serological testing; 100 (43%, 95% confidence interval (CI) 36-49%) had chronic hepatitis C. The median MDI score was 22 (interquartile range 12-33); 32% (95% CI 26-39%) had a score compatible with depression and 14% (95% CI 10-19%) were rated as severe depression. Depression was not associated with hepatitis C (HCV-infected 29%, non-infected 35%; p = 0.25). Forty-one percent (11/27) of the evaluated participants started antidepressant treatment. CONCLUSIONS Our study demonstrated a high prevalence of depressive symptoms among drug users, but this was not more frequent among HCV-infected patients. The high overall prevalence of depression underlines the relevance of screening for depression in patients who are drug users.
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Affiliation(s)
- Lone W Madsen
- From the Department of Infectious Diseases, Odense University Hospital , Denmark
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Snow KK, Bell MC, Stoddard AM, Curto TM, Wright EC, Dienstag JL. Processes to manage analyses and publications in a phase III multicenter randomized clinical trial. Trials 2014; 15:159. [PMID: 24886378 PMCID: PMC4040510 DOI: 10.1186/1745-6215-15-159] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2013] [Accepted: 04/24/2014] [Indexed: 02/07/2023] Open
Abstract
Background The timely publication of findings in peer-reviewed journals is a primary goal of clinical research. In clinical trials, the processes leading to publication can be complex from choice and prioritization of analytic topics through to journal submission and revisions. As little literature exists on the publication process for multicenter trials, we describe the development, implementation, and effectiveness of such a process in a multicenter trial. Methods The Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial included a data coordinating center (DCC) and clinical centers that recruited and followed more than 1,000 patients. Publication guidelines were approved by the steering committee, and the publications committee monitored the publication process from selection of topics to publication. Results A total of 73 manuscripts were published in 23 peer-reviewed journals. When manuscripts were closely tracked, the median time for analyses and drafting of manuscripts was 8 months. The median time for data analyses was 5 months and the median time for manuscript drafting was 3 months. The median time for publications committee review, submission, and journal acceptance was 7 months, and the median time from analytic start to journal acceptance was 18 months. Conclusions Effective publication guidelines must be comprehensive, implemented early in a trial, and require active management by study investigators. Successful collaboration, such as in the HALT-C trial, can serve as a model for others involved in multidisciplinary and multicenter research programs. Trial registration The HALT-C Trial was registered with clinicaltrials.gov (NCT00006164).
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Affiliation(s)
| | | | | | - Teresa M Curto
- New England Research Institutes, 9 Galen Street, Watertown, MA 02472, USA.
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Stewart CA, Enders FTB, Mitchell MM, Felmlee-Devine D, Smith GE. The cognitive profile of depressed patients with cirrhosis. Prim Care Companion CNS Disord 2013; 13:10m01090. [PMID: 21977378 DOI: 10.4088/pcc.10m01090] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2010] [Accepted: 11/22/2010] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVE To determine whether patients with cirrhosis and depressive symptoms have a different neuropsychological cognitive profile from patients with cirrhosis without depressive symptoms in order to show that cirrhosis may not be the only cause for cognitive decline in patients with cirrhosis. METHOD Adult outpatients with a diagnosis of cirrhosis based on histologic findings and clinical characteristics, who did not have clinically overt hepatic encephalopathy and who were being treated in the advanced liver disease and liver transplant clinics, were recruited for the study from May 2003 to May 2006. Patients underwent neuropsychological testing and evaluation for depression using the Beck Depression Inventory-II (BDI-II). Age-adjusted standard neuropsychological domain scores were compared between depressed (BDI-II score ≥ 14) and nondepressed (BDI-II score < 14) patients. RESULTS Seventy-five subjects were included in the study. The 23 patients with depression were similar to the 52 nondepressed patients in level of education, age, and race; the laboratory parameters of international normalized ratio, bilirubin, creatinine, and albumin concentration; and Model for End-Stage Liver Disease scores. There was a higher percentage of women in the depressed group than in the nondepressed group, with a trend toward significance (52% vs 29%; P = .07). No etiology of liver disease was associated with depression. In linear regression analyses, decreases in cognitive function were associated with higher BDI-II scores for the domains of working memory (P = .026), with a trend toward significance for visual-perception (P = .056). Approximately 7% of the variability in working memory score was predicted using the BDI score. CONCLUSIONS Depressive symptoms are associated with worsened cognitive function in cirrhosis.
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Affiliation(s)
- Charmaine A Stewart
- The Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, Minnesota, USA
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Umaki TM, Denney RL. Neurocognitive deficits associated with the hepatitis C virus among incarcerated men. Clin Neuropsychol 2013; 27:426-36. [PMID: 23343198 DOI: 10.1080/13854046.2012.758315] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
The purpose of this preliminary study was to examine cognitive functioning in inmates with the hepatitis C virus (HCV) and to investigate relationships among performance on the Repeatable Battery for the Assessment of Neuropsychological Status-Form A (RBANS; Randolph, 1998). Data from 43 HCV+ inmates were reviewed retrospectively and compared with a sample of HCV- inmates. Significant differences were found on two of five indices (Attention: U = 537.5, p = .003; r = -.32; Total: U = 643.0, p = .048; r = -.22) and four subtests: Coding (U = 326.0, p <.001, r = -.53), Digit Span (U = 634.0, p = .038, r = -.22), Story Memory (U = 625.5, p = .032, r = -.24), and Story Recall (U = 548.5, p = .004, r = -.31), with the HCV group scoring lower on all significant measures. In this study the RBANS proved to be an efficient measure with clinical utility among an HCV population. Within this incarcerated population patterns of performance were "typical" of current literature, with impaired attention appearing earlier in the disease process, and the study invites further exploration into proposed cognitive deficits among this population where HCV is highly prevalent.
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Affiliation(s)
- Tracie M Umaki
- University of Hawaii at Manoa, John A. Burns School of Medicine, Hawaii Center for AIDS, Honolulu, HI 96816, USA.
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Abstract
Chronic infection with hepatitis C virus (HCV) is associated with a wide spectrum of extrahepatic manifestations, affecting different organ systems. Neurological complications occur in a large number of patients and range from peripheral neuropathy to cognitive impairment. Pathogenetic mechanisms responsible for nervous system dysfunction are mainly related to the upregulation of the host immune response with production of autoantibodies, immune complexes, and cryoglobulins. Alternative mechanisms include possible extrahepatic replication of HCV in neural tissues and the effects of circulating inflammatory cytokines and chemokines.
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Evon DM, Golin CE, Fried MW, Keefe FJ. Chronic hepatitis C and antiviral treatment regimens: where can psychology contribute? J Consult Clin Psychol 2012; 81:361-74. [PMID: 22730952 DOI: 10.1037/a0029030] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVE Our goal was to evaluate the existing literature on psychological, social, and behavioral aspects of chronic hepatitis C viral (HCV) infection and antiviral treatment; provide the state of the behavioral science in areas that presently hinder HCV-related health outcomes; and make recommendations for areas in which clinical psychology can make significant contributions. METHOD The extant literature on HCV and antiviral therapy was reviewed as related to biopsychosocial factors such as mental health, substance/alcohol use, quality of life, coping, stigma, racial disparities, side effects, treatment adherence, integrated care, and psychological interventions. RESULTS For reasons that have not been well elucidated, individuals infected with HCV experience psychological and somatic problems and report poor health-related quality of life. Preexisting conditions, including poor mental health and alcohol/substance use, can interfere with access to and successful completion of HCV treatment. Perceived stigma is highly prevalent and associated with psychological distress. Racial disparities exist for HCV prevalence, treatment uptake, and treatment success. During HCV treatment, patients experience exacerbation of symptoms, treatment side effects, and poorer quality of life, making it difficult to complete treatment. Despite pharmacological advances in HCV treatment, improvements in clinical and public health outcomes have not been realized. The reasons for this lack of impact are multifactorial, but include suboptimal referral and access to care for many patients, treatment-related side effects, treatment nonadherence, and lack of empirically based approaches. CONCLUSIONS Biomedical advances in HCV and antiviral treatment have created a fertile field in which psychologists are uniquely positioned to make important contributions to HCV management and treatment.
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Affiliation(s)
- Donna M Evon
- Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7584, USA. Donna_
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Montagnese S, Schiff S, De Rui M, Crossey MME, Amodio P, Taylor-Robinson SD. Neuropsychological tools in hepatology: a survival guide for the clinician. J Viral Hepat 2012; 19:307-15. [PMID: 22497809 DOI: 10.1111/j.1365-2893.2012.01592.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Neuropsychological assessment has three main applications in clinical hepatology: (i) to detect, grade and monitor liver failure-related cognitive alterations in end-stage liver disease (hepatic encephalopathy), (ii) to substantiate complaints of attention or concentration difficulties in patients with non-cirrhotic chronic hepatitis C viral infection, and (iii) to screen patients who are being considered for liver transplantation for early signs of dementia. However, there is limited agreement on how cognitive assessment should be conducted in these patients, and how results should be interpreted and used to implement clinical decisions. In this review, we summarize the available literature on neuropsychological dysfunction in patients with cirrhosis and with chronic hepatitis C viral infection and provide some guidance on how to utilize neuropsychological assessment in practice.
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Affiliation(s)
- S Montagnese
- Department of Clinical and Experimental Medicine, University of Padova, Padova, Italy
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Senzolo M, Schiff S, D’Aloiso CM, Crivellin C, Cholongitas E, Burra P, Montagnese S. Neuropsychological alterations in hepatitis C infection: The role of inflammation. World J Gastroenterol 2011; 17:3369-74. [PMID: 21876628 PMCID: PMC3160562 DOI: 10.3748/wjg.v17.i29.3369] [Citation(s) in RCA: 61] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2010] [Revised: 01/14/2011] [Accepted: 01/21/2011] [Indexed: 02/06/2023] Open
Abstract
About 50% of patients with hepatitis C virus (HCV) infection complain of neuropsychiatric symptoms, “brain fog”, weakness, fatigue, and exhibit some degree of quality of life impairment, irrespective of the severity of liver disease. Since the first observation of HCV-related cognitive deficits, 10 studies have been published that have evaluated neuropsychiatric performance in patients with HCV infection and different degrees of hepatic impairment. Unfortunately, these have often included patients with cirrhosis, patients who had acquired the infection through previous intravenous drug misuse, who had a history of relatively recent treatment with interferon, or were on psychoactive medication. In addition, different neuropsychological batteries and tests that explored different cognitive domains were used, which makes the results of the studies difficult to compare. Finally, limited information is available on the pathogenesis of HCV-related cognitive impairment. Cerebral and/or systemic inflammation may be important players but their potential role has not been substantiated by experimental data. The present review outlines the available evidence of the presence of cognitive impairment in patients with HCV infection, with a focus on the potential relationship with cerebral and/or systemic inflammation.
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Hilsabeck RC, Anstead GM, Webb AL, Hoyumpa A, Stern SL. Author response. J Neuroimmunol 2011. [DOI: 10.1016/j.jneuroim.2010.10.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Kronfol Z, Litman HJ, Back-Madruga C, Bieliauskas LA, Lindsay KL, Lok AS, Fontana RJ. No increase in depression with low-dose maintenance peginterferon in prior non-responders with chronic hepatitis C. J Affect Disord 2011; 129:205-12. [PMID: 20889211 PMCID: PMC3025085 DOI: 10.1016/j.jad.2010.09.010] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2010] [Accepted: 09/15/2010] [Indexed: 01/22/2023]
Abstract
BACKGROUND Peginterferon and ribavirin treatment of chronic hepatitis C (CHC) is frequently associated with dose-limiting neuropsychiatric toxicity. The purpose of this study is to determine whether prolonged administration of low-dose peginterferon-α2a is associated with an increase in the rate and severity of depression compared to untreated controls. METHODS 129 non-responders to full-dose peginterferon and ribavirin treatment were randomized to low-dose maintenance treatment with peginterferon-α2a 90 μg/week or no treatment for 3.5 years. Depression was assessed using the Beck Depression Inventory (BDI-II) and the Composite International Diagnostic Interview (CIDI) at baseline and at 12, 24, 36, and 48 months. "Clinical depression" was defined as BDI-II ≥11 and/or meeting DSM-IV criteria for major depression on the CIDI. Serial cortisol and serotonin plasma concentrations were obtained in a subgroup of patients. RESULTS Rates of clinical depression did not significantly differ over time or between treatment groups. Baseline clinical depression was the only significant predictor of clinical depression over time (p<0.001). Rates of clinical depression were also significantly higher in patients experiencing liver disease progression (p=0.016). Antidepressant use did not significantly differ between groups. Adjusted whole blood serotonin levels dropped significantly over time (p=0.04), but there was no group by time effect. LIMITATIONS Lack of significant group differences in antidepressant use does not completely preclude significant mood changes masked by antidepressants. Results may differ in treatment naïve CHC patients or in those receiving full-dose peginterferon. CONCLUSIONS Prolonged low-dose peginterferon-α2a treatment is not associated with an increase in the frequency or severity of clinical depression in prior non-responder patients with chronic hepatitis C.
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Affiliation(s)
- Ziad Kronfol
- Depression Center, University of Michigan, Ann Arbor, MI
| | | | - Carla Back-Madruga
- Department of Psychiatry and the Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA
| | - Linas A. Bieliauskas
- Neuropsychology Section, Department of Psychiatry, University of Michigan, Ann Arbor, MI
- Psychology Service, Veterans Affairs Health System, Ann Arbor, MI
| | - Karen L. Lindsay
- Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA
| | - Anna S. Lok
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI
| | - Robert J. Fontana
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI
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Jacobson IM, Cacoub P, Dal Maso L, Harrison SA, Younossi ZM. Manifestations of chronic hepatitis C virus infection beyond the liver. Clin Gastroenterol Hepatol 2010; 8:1017-29. [PMID: 20870037 DOI: 10.1016/j.cgh.2010.08.026] [Citation(s) in RCA: 118] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2010] [Revised: 08/20/2010] [Accepted: 08/24/2010] [Indexed: 02/06/2023]
Abstract
In addition to its effects in the liver, chronic hepatitis C virus (HCV) infection can have serious consequences for other organ systems. Extrahepatic manifestations include mixed cryoglobulinemia (MC) vasculitis, lymphoproliferative disorders, renal disease, insulin resistance, type 2 diabetes, sicca syndrome, rheumatoid arthritis-like polyarthritis, and autoantibody production; reductions in quality of life involve fatigue, depression, and cognitive impairment. MC vasculitis, certain types of lymphoma, insulin resistance, and cognitive function appear to respond to anti-HCV therapy. However, treatments for HCV and other biopsychosocial factors can reduce quality of life and complicate management. HCV treatment has a high overall cost that increases when extrahepatic manifestations are considered. HCV appears to have a role in the pathogenesis of MC vasculitis, certain types of lymphoma, and insulin resistance. Clinicians who treat patients with HCV infections should be aware of potential extrahepatic manifestations and how these can impact and alter management of their patients.
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Affiliation(s)
- Ira M Jacobson
- Center for the Study of Hepatitis C, Joan and Sanford I. Weill Medical College of Cornell University, New York, New York 10021, USA.
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Posada C, Moore DJ, Woods SP, Vigil O, Ake C, Perry W, Hassanein TI, Letendre SL, Grant I. Implications of hepatitis C virus infection for behavioral symptoms and activities of daily living. J Clin Exp Neuropsychol 2010; 32:637-44. [PMID: 20603743 DOI: 10.1080/13803390903418900] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Hepatitis C virus (HCV) is neurovirulent and has been shown to be associated with neuropsychological (NP) deficits in a subset of infected individuals. Despite these previous findings, little work has been done to examine neurobehavioral symptoms associated with HCV infection. We examined 34 HCV seropositive (HCV+) individuals and 35 healthy comparison participants (HCV-) with the self-rating form of the Frontal Systems Behavior Scale (FrSBe). Results showed that at the group level, only the FrSBe apathy subscale mean was clinically elevated (T score >65) among HCV+ persons; executive dysfunction, disinhibition, and total subscale means were not clinically elevated. At the individual level, a significantly higher proportion of HCV+ individuals than of HCV- individuals reported clinically elevated FrSBe T scores . Moreover, HCV+ individuals were nearly 3 times as likely to report clinically elevated FrSBe T scores of apathy, executive dysfunction, and disinhibition as compared to HCV- participants. A multiple regression that included substance use disorders, neuropsychological impairment, and age indicated that HCV status was an independent predictor of self-reported FrSBe total T scores. Across all participants, small, yet significant, correlations were found between elevated self-reported FrsBe T scores and dependence in activities of daily living. These results show that a subset of HCV-infected individuals report clinically elevated behavioral symptoms. Clinical implications for the assessment and management of elevated behavioral symptoms in HCV are discussed.
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Affiliation(s)
- Carolina Posada
- San Diego State University/University of California, San Diego Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA
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Fontana RJ, Bieliauskas L, Back-Madruga C, Lindsay KL, Litman HJ, Lok AS, Kronfol Z. Cognitive function does not worsen during long-term low-dose peginterferon therapy in patients with chronic hepatitis C. Am J Gastroenterol 2010; 105:1551-60. [PMID: 20104219 PMCID: PMC3772520 DOI: 10.1038/ajg.2010.3] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Neuropsychiatric toxicity is a common dose-limiting side effect of interferon therapy. The primary aim of this study was to determine whether patients receiving long-term low-dose peginterferon therapy had a higher incidence of cognitive side effects compared with untreated patients enrolled in the Hepatitis C Antiviral Long-Term treatment against Cirrhosis (HALT-C) Trial. METHODS A total of 129 patients with chronic hepatitis C and advanced fibrosis completed a battery of 10 neuropsychological tests and the Beck Depression Inventory at pretreatment baseline and at months 12, 24, 36, and 48 while receiving long-term peginterferonalpha2a (90 microg/week) or no therapy during the randomized phase of the HALT-C Trial. Cognitive impairment was defined as a global deficit score (GDS) > or = 1.0. RESULTS The mean age was 51.2 years, 67% were male, and 42% had cirrhosis. After accounting for baseline GDS scores, the mean GDS scores did not significantly change over time (P=0.46) nor with treatment group (P=0.49). Cognitive function was also not influenced by medication adherence in the 66 patients receiving maintenance peginterferon (P=0.14) after controlling for baseline GDS scores and time. Beck Depression scores did not significantly increase over time (P=0.60), nor did they vary by treatment group (P=0.74). Although 32% of patients experienced objective worsening of their liver disease during follow-up, the frequency and severity of cognitive impairment did not differ in those with and without disease progression (P=0.71). CONCLUSIONS Measures of cognitive function were neither influenced by low-dose peginterferon treatment nor with objective evidence of liver disease progression in patients with advanced chronic hepatitis C prospectively followed up for 3.5 years.
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Affiliation(s)
- Robert J. Fontana
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI
| | - Linas Bieliauskas
- Neuropsychology Section, Department of Psychiatry, University of Michigan, Ann Arbor, MI,Psychology Service, Veterans Affairs Health System, Ann Arbor, MI
| | - Carla Back-Madruga
- Department of Psychiatry and the Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA
| | - Karen L Lindsay
- Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA
| | | | - Anna S.F. Lok
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI
| | - Ziad Kronfol
- Depression Center, University of Michigan, Ann Arbor, MI
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Lowry D, Coughlan B, McCarthy O, Crowe J. Investigating health-related quality of life, mood and neuropsychological test performance in a homogeneous cohort of Irish female hepatitis C patients. J Viral Hepat 2010; 17:352-9. [PMID: 19758275 DOI: 10.1111/j.1365-2893.2009.01188.x] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Neurocognitive dysfunction has been reported in individuals with chronic hepatitis C (CHC) infection, but HCV populations investigated have often included participants with numerous potential confounding comorbidities. This pilot study sought to investigate functional capacity and neurocognitive function in a homogeneous state-infected HCV population with histologically defined mild liver disease, free from the comorbid factors typically associated with HCV populations. A further aim was to examine cognitive function in a treatment naive population with a similar history of iatrogenic HCV exposure and spontaneous viral clearance. A convenience sample of 29 women, all of whom were carefully screened to exclude relevant comorbidities, was recruited to the study. Twenty women with a history of iatrogenic HCV exposure were recruited from prospective specialist tertiary care liver clinics. A comparison group of healthy controls (n = 9) was also assessed. Study participants underwent mood, health-related quality of life and neuropsychological assessment. CHC patients reported significantly higher levels of cognitive fatigue than healthy controls (F = 3.4, P = 0.04). On cognitive testing, CHC patients showed impairments compared with healthy controls on estimates of general memory [F(2,25) = 4.1, P = 0.03, partial eta squared = 0.25], delayed auditory recognition [F(2,25) = 4.2, P = 0.03, partial eta squared= 0.22] and sustained attention [F(2,25) = 3.6, P = 0.04, partial eta squared = 0.22]. Increased cognitive fatigue only correlated with delayed auditory memory recall ability (r = 0.724, P = 0.006). In conclusion, these findings appear to support the presence of neurocognitive abnormalities in an iatrogenically infected, homogeneous female HCV population who were carefully screened to eliminate other factors affecting neurocognitive test performance and may indicate underlying neurophysiological causative mechanisms.
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Affiliation(s)
- D Lowry
- Centre for Liver Disease, Mater Misericordiae University Hospital, 55 Eccles Street, Dublin 7, Ireland.
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Hilsabeck RC, Anstead GM, Webb AL, Hoyumpa A, Ingmundson P, Holliday S, Zhang Q, Casas AM, Jovel M, Stern SL. Cognitive efficiency is associated with endogenous cytokine levels in patients with chronic hepatitis C. J Neuroimmunol 2010; 221:53-61. [DOI: 10.1016/j.jneuroim.2010.01.017] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2009] [Revised: 01/13/2010] [Accepted: 01/29/2010] [Indexed: 01/18/2023]
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Michitaka K, Hiraoka A, Kume M, Uehara T, Hidaka S, Ninomiya T, Hasebe A, Miyamoto Y, Ichiryu M, Tanihira T, Nakahara H, Ochi H, Tanabe A, Uesugi K, Tokumoto Y, Mashiba T, Abe M, Hiasa Y, Matsuura B, Onji M. Amino acid imbalance in patients with chronic liver diseases. Hepatol Res 2010; 40:393-8. [PMID: 20236360 DOI: 10.1111/j.1872-034x.2009.00614.x] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
AIM The aim of this study is to clarify the amino acid imbalance in patients with chronic hepatitis (CH) as well as those with liver cirrhosis (LC). METHODS We assayed total branched-chain amino acids (BCAA), tyrosine (Tyr) levels and their ratio (BTR) in sera of 101 patients with CH (37 in fibrosis stage F1, 23 in F2, 21 in F3) and 20 with LC (F4) who were diagnosed by liver biopsy. Their levels in relation to the staging of liver fibrosis were analyzed. RESULTS The percentage of patients whose BTR was less than the normal range was 32.1% in CH and 75.0% in LC. The levels of BTR and BCAA were significantly lower (P < 0.001, P < 0.05, respectively) and that of Tyr was significantly higher (P < 0.001) in patients with LC than those in CH. The levels of BTR decreased according to the staging. The levels of Tyr increased according the staging, whereas the levels of BCAA deceased prominently in F4 (487 +/- 103 in F1, 483 +/- 122 in F2, 487 +/- 111 in F3 and 423 +/- 94 in F4). CONCLUSION A considerable number of patients not only with LC but also with CH showed lower levels of BTR. It has been clarified that amino acid imbalance of Tyr was found in the early stage of liver disease, whereas decrease of BCAA was found mainly in F4 stage.
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Affiliation(s)
- Kojiro Michitaka
- Department of Gastroenterology, Ehime Prefectural Central Hospital, Matsuyama
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Wobrock T, Mihm U, Löhr C, Hofmann WP, Sarrazin C, Zeuzem S, Falkai P. Cognition in hepatitis C patients treated with pegylated interferon. World J Biol Psychiatry 2010; 10:819-26. [PMID: 19995219 DOI: 10.1080/15622970701714362] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
Neuropsychiatric symptoms are frequently reported by patients with chronic hepatitis C during treatment with interferon (IFN)-alpha and may lead to treatment discontinuation. In order to assess the objective neuropsychiatric impairments we prospectively administered standardized neuropsychological testing before and 3 months after the initiation of antiviral treatment with pegylated IFN-alpha in 17 patients suffering from chronic hepatitis C. In addition depression and anxiety scores, social functioning and hepatological parameters were obtained. While depressive and anxiety symptoms increased significantly during treatment only subtle worsening in neurocognitive performance could be detected, indicating slight impairment in cognitive flexibility and psychomotor speed (Trail Making Test B; 69.6+/-23 s before vs. 80.7+/-31 s during therapy, P=0.011, not remaining significant after Bonferroni correction). We found no association between reduced neurocognitive performance and the severity of depression. Better neurocognitive performance in single domains was associated with better response to antiviral treatment measured as the decline of elevated liver enzymes (AST). We conclude that neurocognitive performance was influenced by antiviral IFN-alpha-based combination treatment only in single domains and not to a clinically relevant extent in contrast to the significant worsening of depression.
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Affiliation(s)
- Thomas Wobrock
- Department of Psychiatry and Psychotherapy, Georg-August University Göttingen, Göttingen, Germany.
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Björnsson E, Verbaan H, Oksanen A, Frydén A, Johansson J, Friberg S, Dalgård O, Kalaitzakis E. Health-related quality of life in patients with different stages of liver disease induced by hepatitis C. Scand J Gastroenterol 2010; 44:878-87. [PMID: 19437190 DOI: 10.1080/00365520902898135] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Patients with hepatitis C have been shown to have impaired health-related quality of life (HRQoL). The aim of this study was to determine HRQoL in patients in different stages of hepatitis C virus (HCV) and to compare HRQoL in HCV cirrhosis with non-HCV-induced cirrhosis. MATERIAL AND METHODS Out of 489 consecutive patients who fulfilled the inclusion criteria, 472 (96%) agreed to participate in the study: 158 patients with mild/moderate fibrosis with chronic hepatitis C (CHC group), 76 patients with HCV compensated cirrhosis (CC), 53 patients with HCV decompensated (DC) cirrhosis, 52 non-cirrhotic patients with sustained viral response (SVR), and a control group consisting of 32 patients with non-HCV CC and 101 with non-HCV DC who completed the Short Form-36 (SF-36) and EQ-5D questionnaire. RESULTS The CHC group had significantly lower SF-36 scores than healthy controls, with the exception of scores for the dimensions physical function and bodily pain. HCV patients with DC had lower scores in all SF-36 dimensions in comparison with those of the CHC group, as well as in physical and mental component summaries (p<0.001). In comparison with the CHC group, the HCV CC group had lower scores on the SF-36 general health dimension (p<0.05) and lower SF-36 physical component summary (PCS) scores (p<0.05). No major differences were seen in patients with HCV- and non-HCV-induced cirrhosis. CONCLUSIONS Impairment in HRQoL in patients with HCV was associated with the severity of liver disease, patients with decompensated cirrhosis exhibiting the highest impairment in HRQoL. The etiology of liver disease does not seem to be important in determining HRQoL in cirrhosis.
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Affiliation(s)
- Einar Björnsson
- Department of Internal Medicine, Section of Gastroenterology and Hepatology, Sahlgrenska University Hospital, Gothenburg, Sweden.
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