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Chelouah S, Nna H, Angijiro P, Thomas F, Thavaseelan R, Januel D, Yekhlef W. Screening, Prevalence and Management of Chronic Viral Hepatitis C in Mental Health Setting: Towards the Eradication of A Forgotten Reservoir. J Viral Hepat 2025; 32:e70014. [PMID: 39976344 DOI: 10.1111/jvh.70014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 02/08/2025] [Accepted: 02/10/2025] [Indexed: 02/21/2025]
Abstract
The rate of HCV infection is higher in people with psychiatric conditions than in the general population. However, access to somatic care for populations with mental or dual diagnoses remains insufficient. These circumstances could constitute a barrier to the eradication of HCV infection. A retrospective study was performed in the public mental health institution of Ville Evrard. Screening for HCV infection should be systematically proposed to patients attending the institution. On-site assessment of liver disease severity and treatment with direct-acting antivirals prescribed by physicians not specialised in hepatology allowed a better continuum of care. Patients lost to follow-up after a positive HCV serology test without viral load assessment were contacted. Patients hospitalised at least once a year were included. 8520 patients out of 18,439 (46.2%) were screened for HCV infection between 2017 and 2021. The screening rate increased from 40.0% in 2017 to 65.7% in 2021. HCV seroprevalence was 2.2%. A total of 129 HCV PCRs were performed, and 27.1% were positive. In a logistic regression model, patients older than 30 years were at greater risk of having a positive HCV serology test. These positive serologies were 1.9 times higher in men than women (p < 0.001). The assessment of fibrosis was found in 45.7% of patients with a positive HCV PCR. Patients with psychiatric conditions constitute an important HCV reservoir. A strategy of screening and management of HCV infection in this population appears to be feasible. This strategy could contribute to the eradication of chronic HCV infection.
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Affiliation(s)
- Sonia Chelouah
- Service des Spécialités et Médecine Polyvalente, pôle CRISTALES (Coordination pour la Recherche et l'Information, les Soins, les Thérapeutiques, les Analyses de Laboratoire et l'Éducation à la Santé), Établissement Public de Santé de Ville-Evrard, Neuilly-sur-Marne, France
- Département de Recherche Clinique, pôle Universitaire 93G03, Établissement Public de Santé de Ville-Evrard, Neuilly-sur-Marne, France
| | - Harmonie Nna
- Service des Spécialités et Médecine Polyvalente, pôle CRISTALES (Coordination pour la Recherche et l'Information, les Soins, les Thérapeutiques, les Analyses de Laboratoire et l'Éducation à la Santé), Établissement Public de Santé de Ville-Evrard, Neuilly-sur-Marne, France
| | - Paul Angijiro
- Service des Spécialités et Médecine Polyvalente, pôle CRISTALES (Coordination pour la Recherche et l'Information, les Soins, les Thérapeutiques, les Analyses de Laboratoire et l'Éducation à la Santé), Établissement Public de Santé de Ville-Evrard, Neuilly-sur-Marne, France
| | - Fanny Thomas
- Département d'Information Médicale, pôle CRISTALES, Établissement Public de Santé de Ville-Evrard, Neuilly-sur-Marne, France
| | - Rusheenthira Thavaseelan
- Département de Recherche Clinique, pôle Universitaire 93G03, Établissement Public de Santé de Ville-Evrard, Neuilly-sur-Marne, France
| | - Dominique Januel
- Département de Recherche Clinique, pôle Universitaire 93G03, Établissement Public de Santé de Ville-Evrard, Neuilly-sur-Marne, France
- Université Sorbonne Paris Nord, Bobigny, France
| | - Wanda Yekhlef
- Service des Spécialités et Médecine Polyvalente, pôle CRISTALES (Coordination pour la Recherche et l'Information, les Soins, les Thérapeutiques, les Analyses de Laboratoire et l'Éducation à la Santé), Établissement Public de Santé de Ville-Evrard, Neuilly-sur-Marne, France
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Polukchi TV. Cognitive Impairments in Viral Hepatitis Patients: Causes, Manifestations, and Impact on Quality of Life. Rambam Maimonides Med J 2025; 16:RMMJ.10539. [PMID: 39879545 PMCID: PMC11779499 DOI: 10.5041/rmmj.10539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2025] Open
Abstract
Viral hepatitis, primarily caused by hepatitis B virus and hepatitis C virus, is widely recognized for its impact on liver function, but emerging evidence suggests it also affects cognitive function. This review explores the causes, manifestations, and impact of cognitive impairments in patients with viral hepatitis, to better understand this often-overlooked aspect of the disease. A literature review was conducted, focusing on studies published in PubMed up to August 2024. Key areas covered include the pathophysiological mechanisms behind cognitive impairment in viral hepatitis, clinical manifestations observed in affected patients, the implications for their daily functioning and overall well-being, and the tools used in cognitive assessments. Common manifestations included deficits in attention, memory, executive function, and psychomotor speed. These cognitive challenges can significantly impact daily activities, occupational performance, and social interactions, contributing to reduced quality of life. Cognitive impairments in viral hepatitis patients represent a significant concern that extends beyond liver health. Recognizing and addressing these cognitive issues are crucial for improving patient outcomes. Enhanced diagnostic strategies and targeted interventions are needed to better manage cognitive symptoms and support affected individuals in maintaining their quality of life. This narrative review aims to enhance clinical practice and inform future research directions.
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Kazmi SMA, Iftikhar R. Cross cutting symptoms, liver function and perceived immune status as predictors of quality of life in patients with Hepatitis B and C: the mediating role of social support and resilience. CURRENT PSYCHOLOGY 2024; 43:29954-29963. [DOI: 10.1007/s12144-024-06530-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/06/2024] [Indexed: 01/04/2025]
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Fakoury MK, Schmidt SL, Brandão Mello CE, Filho ADC, Amendola Pires MM. Cognitive Performance in Asymptomatic Elderly People with Hepatitis C: The Role of Education. J Clin Med 2023; 12:4588. [PMID: 37510703 PMCID: PMC10380825 DOI: 10.3390/jcm12144588] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Revised: 07/05/2023] [Accepted: 07/05/2023] [Indexed: 07/30/2023] Open
Abstract
BACKGROUND Neurotropism of the hepatitis C virus (HCV) can be the source of subtle neuropsychological symptoms in non-cirrhotic patients. Age is a risk factor for cognitive impairment (CI). Thus, asymptomatic elderly people who carry HCV might be at a greater risk of CI. Education can influence test performance. OBJECTIVES (1) To verify whether elderly people with HCV performed poorer than controls on cognitive tests. (2) To analyze how education affects performance. (3) To verify whether the extent of the effect of education on performance depends on the group (HCV vs. controls) and the type of cognitive test. METHODS Asymptomatic HCV carriers older than 60 years (n = 41) were matched with 41 corresponding controls. All participants performed the following tests: Mini-Cog, Mini Mental State Examination, clock drawing test (CDT), and verbal fluency. RESULTS (1) There were no significant differences in cognitive performance between the two groups. (2) Higher education was always associated with better performance. (3) There was a significant group difference in the slopes of the regression lines between years of education and CDT performance. No differences were found for the other three tests. CONCLUSION Considering the scores on the CDT, the rate of improvement in performance when schooling increases is higher in HCV carriers.
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Affiliation(s)
- Max Kopti Fakoury
- Department of Internal Medicine, Gaffrée and Guinle University Hospital, Federal University of the State of Rio de Janeiro, Rio de Janeiro 21941-853, Brazil
- Graduate Program in Neurology, Department of Neurology, PPGNEURO-UNIRIO, Federal University of the State of Rio de Janeiro, Rio de Janeiro 21941-853, Brazil
- Laboratory of Behavioral Neurology, Federal University of the State of Rio de Janeiro, Rio de Janeiro 21941-853, Brazil
- RENASCER Multidisciplinary Program of the Third Age, Gaffrée and Guinle University Hospital, Federal University of the State of Rio de Janeiro, Rio de Janeiro 21941-853, Brazil
| | - Sergio Luis Schmidt
- Graduate Program in Neurology, Department of Neurology, PPGNEURO-UNIRIO, Federal University of the State of Rio de Janeiro, Rio de Janeiro 21941-853, Brazil
- Laboratory of Behavioral Neurology, Federal University of the State of Rio de Janeiro, Rio de Janeiro 21941-853, Brazil
- RENASCER Multidisciplinary Program of the Third Age, Gaffrée and Guinle University Hospital, Federal University of the State of Rio de Janeiro, Rio de Janeiro 21941-853, Brazil
| | - Carlos Eduardo Brandão Mello
- Department of Internal Medicine, Gaffrée and Guinle University Hospital, Federal University of the State of Rio de Janeiro, Rio de Janeiro 21941-853, Brazil
- Graduate Program in Neurology, Department of Neurology, PPGNEURO-UNIRIO, Federal University of the State of Rio de Janeiro, Rio de Janeiro 21941-853, Brazil
- Graduate Program in HIV/AIDS Infection and Viral Hepatitis, PPGHIV/HV-UNIRIO, School of Medicine and Surgery, Federal University of the State of Rio de Janeiro, Rio de Janeiro 21941-853, Brazil
| | - Aureo do Carmo Filho
- Graduate Program in Neurology, Department of Neurology, PPGNEURO-UNIRIO, Federal University of the State of Rio de Janeiro, Rio de Janeiro 21941-853, Brazil
- Laboratory of Behavioral Neurology, Federal University of the State of Rio de Janeiro, Rio de Janeiro 21941-853, Brazil
| | - Marcia Maria Amendola Pires
- Graduate Program in Neurology, Department of Neurology, PPGNEURO-UNIRIO, Federal University of the State of Rio de Janeiro, Rio de Janeiro 21941-853, Brazil
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Dybowska D, Zarębska-Michaluk D, Rzymski P, Berak H, Lorenc B, Sitko M, Dybowski M, Mazur W, Tudrujek-Zdunek M, Janocha-Litwin J, Janczewska E, Klapaczyński J, Parfieniuk-Kowerda A, Piekarska A, Sobala-Szczygieł B, Dobrowolska K, Pawłowska M, Flisiak R. Real-world effectiveness and safety of direct-acting antivirals in hepatitis C virus patients with mental disorders. World J Gastroenterol 2023; 29:4085-4098. [PMID: 37476581 PMCID: PMC10354581 DOI: 10.3748/wjg.v29.i25.4085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 04/01/2023] [Accepted: 04/28/2023] [Indexed: 06/28/2023] Open
Abstract
BACKGROUND It is estimated that 58 million people worldwide are infected with the hepatitis C virus (HCV). Patients with severe psychiatric disorders could not be treated with previously available interferon-based therapies due to their unfavorable side effect profile. This has changed with the introduction of direct-acting antivirals (DAA), although their real-life tolerance and effectiveness in patients with different psychiatric disorders remain to be demonstrated. AIM To evaluate the effectiveness and safety of DAA in patients with various mental illnesses. METHODS This was a retrospective observational study encompassing 14272 patients treated with DAA for chronic hepatitis C in 22 Polish hepatology centers, including 942 individuals diagnosed with a mental disorder (anxiety disorder, bipolar affective disorder, depression, anxiety-depressive disorder, personality disorder, schizophrenia, sleep disorder, substance abuse disorder, and mental illness without a specific diagnosis). The safety and effectiveness of DAA in this group were compared to those in a group without psychiatric illness (n = 13330). Antiviral therapy was considered successful if serum ribonucleic acid (RNA) of HCV was undetectable 12 wk after its completion [sustained virologic response (SVR)]. Safety data, including the incidence of adverse events (AEs), serious AEs (SAEs), and deaths, and the frequency of treatment modification and discontinuation, were collected during therapy and up to 12 wk after treatment completion. The entire study population was included in the intent-to-treat (ITT) analysis. Per-protocol (PP) analysis concerned patients who underwent HCV RNA evaluation 12 wk after completing treatment. RESULTS Among patients with mental illness, there was a significantly higher percentage of men, treatment-naive patients, obese, human immunodeficiency virus and hepatitis B virus-coinfected, patients with cirrhosis, and those infected with genotype 3 (GT3) while infection with GT1b was more frequent in the population without psychiatric disorders. The cure rate calculated PP was not significantly different in the two groups analyzed, with a SVR of 96.9% and 97.7%, respectively. Although patients with bipolar disorder achieved a significantly lower SVR, the multivariate analysis excluded it as an independent predictor of treatment non-response. Male sex, GT3 infection, cirrhosis, and failure of previous therapy were identified as independent negative predictors. The percentage of patients who completed the planned therapy did not differ between groups with and without mental disorders. In six patients, symptoms of mental illness (depression, schizophrenia) worsened, of which two discontinued treatments for this reason. New episodes of sleep disorders occurred significantly more often in patients with mental disorders. Patients with mental illness were more frequently lost to follow-up (4.2% vs 2.5%). CONCLUSION DAA treatment is safe and effective in HCV-infected patients with mental disorders. No specific psychiatric diagnosis lowered the chance of successful antiviral treatment.
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Affiliation(s)
- Dorota Dybowska
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Nicolaus Copernicus University, Bydgoszcz 85-030, Poland
| | - Dorota Zarębska-Michaluk
- Department of Infectious Diseases and Allergology, Jan Kochanowski University, Kielce 25-317, Poland
- Department of Infectious Diseases, Provincial Hospital, Kielce 25-317, Poland
| | - Piotr Rzymski
- Department of Environmental Medicine, University of Medical Sciences, Poznań 60-806, Poland
- Integrated Science Association, Universal Scientific Education and Research Network, Poznań 60-806, Poland
| | - Hanna Berak
- Outpatient Clinic, Hospital for Infectious Diseases in Warsaw, Warsaw 01-201, Poland
| | - Beata Lorenc
- Pomeranian Center of Infectious Diseases, Medical University, Gdańsk 80-214, Poland
| | - Marek Sitko
- Department of Infectious and Tropical Diseases, Jagiellonian University, Kraków 31-088, Poland
| | - Michał Dybowski
- Utrecht University School of Economics, Utrecht University, Utrecht 3584 EC, Netherlands
| | - Włodzimierz Mazur
- Clinical Department of Infectious Diseases, Medical University of Silesia, Chorzów 41-500, Poland
| | | | - Justyna Janocha-Litwin
- Department of Infectious Diseases and Hepatology, Medical University of Wrocław, Wrocław 50-367, Poland
| | - Ewa Janczewska
- Department of Basic Medical Sciences, Faculty of Public Health in Bytom, Medical University of Silesia, Katowice 40-007, Poland
| | - Jakub Klapaczyński
- Department of Internal Medicine and Hepatology, Central Clinical Hospital of the Ministry of Internal Affairs and Administration, Warsaw 00-241, Poland
| | - Anna Parfieniuk-Kowerda
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok 15-089, Poland
| | - Anna Piekarska
- Department of Infectious Diseases and Hepatology, Medical University of Łódź, Łódź 91-347, Poland
| | - Barbara Sobala-Szczygieł
- Department of Infectious Diseases and Hepatology, Medical University of Silesia, Bytom 41-902, Poland
| | | | - Malgorzata Pawłowska
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Nicolaus Copernicus University, Bydgoszcz 85-030, Poland
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok 15-089, Poland
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Ruck JM, King EA, Chu NM, Segev DL, McAdams-DeMarco M. Cognitive Dysfunction in Liver Disease and Its Implications for Transplant Candidates. CURRENT TRANSPLANTATION REPORTS 2023. [DOI: 10.1007/s40472-023-00390-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
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Acharya C, McGeorge S, Fagan A, Wade JB, Lee H, Luketic V, Sterling RK, Thacker L, Bajaj JS. Substance-use simulation impairs driving capability in patients with cirrhosis regardless of hepatic encephalopathy. Hepatol Commun 2022; 6:2867-2875. [PMID: 35842916 PMCID: PMC9512458 DOI: 10.1002/hep4.2028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 05/16/2022] [Accepted: 06/11/2022] [Indexed: 11/07/2022] Open
Abstract
Driving is independently affected by cirrhosis and hepatic encephalopathy (HE) and alcohol/substance use, but their concomitant impact is unclear. We aimed to determine the impact of alcohol and other substances on driving-simulator performance in cirrhosis with and without HE. Outpatients with cirrhosis and controls underwent cognitive testing and driving simulation for the following three conditions: baseline, wearing goggles simulating alcohol intoxication, and wearing goggles simulating opioid/benzodiazepine abuse. Outcomes were number of centerline crossings (CCs) and road-edge excursions (REEs). We compared controls versus patients with cirrhosis then subjects with cirrhosis with and without HE for all conditions, using generalized linear modeling (GLM). Sixty subjects (17 controls, 43 with cirrhosis [Model for End-Stage Liver Disease score, 10; 21 subjects with prior HE]) were included. Simulations showed higher CCs and REEs at baseline in patients with cirrhosis with and without HE versus controls. With alcohol- and substance abuse-impairment goggles, CCs increased but REEs decreased in cirrhosis. In the GLM, a time and group interaction was seen (p < 0.001) for CCs and REEs. Patients with cirrhosis showed higher CCs and REEs at baseline than controls (CCs, p = 0.003; REEs, p = 0.0001) and higher CCs (p = 0.03) and lower REEs (p = 0.001) with alcohol-simulating goggles. All groups were equally impaired with opioid/benzodiazepine-simulating goggles (CCs, p = 0.49; REEs, p = 0.46). Controls with alcohol-simulating goggles had similar CCs as the baseline of patients with cirrhosis (p = 0.98). conclusions: Simulating alcohol intake induces greater driving impairment in patients with cirrhosis versus controls, but similar patterns were seen with opioid/benzodiazepine-simulating goggles. At baseline, patients with cirrhosis have simulator outcomes equivalent to intoxicated controls. Driving simulation with goggles modeling substance abuse could improve insight into driving errors and enhance driving rehabilitation in patients with cirrhosis.
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Affiliation(s)
- Chathur Acharya
- Division of Gastroenterology, Hepatology, and NutritionVirginia Commonwealth University and Richmond VA Medical CenterRichmondVirginiaUSA
| | - Sara McGeorge
- Division of Gastroenterology, Hepatology, and NutritionVirginia Commonwealth University and Richmond VA Medical CenterRichmondVirginiaUSA
| | - Andrew Fagan
- Division of Gastroenterology, Hepatology, and NutritionVirginia Commonwealth University and Richmond VA Medical CenterRichmondVirginiaUSA
| | - James B. Wade
- Department of PsychiatryVirginia Commonwealth UniversityRichmondVirginiaUSA
| | - Hannah Lee
- Division of Gastroenterology, Hepatology, and NutritionVirginia Commonwealth University and Richmond VA Medical CenterRichmondVirginiaUSA
| | - Velimir Luketic
- Division of Gastroenterology, Hepatology, and NutritionVirginia Commonwealth University and Richmond VA Medical CenterRichmondVirginiaUSA
| | - Richard K. Sterling
- Division of Gastroenterology, Hepatology, and NutritionVirginia Commonwealth University and Richmond VA Medical CenterRichmondVirginiaUSA
| | - Leroy Thacker
- Department of BiostatisticsVirginia Commonwealth UniversityRichmondVirginiaUSA
| | - Jasmohan S. Bajaj
- Division of Gastroenterology, Hepatology, and NutritionVirginia Commonwealth University and Richmond VA Medical CenterRichmondVirginiaUSA
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Ramos A, Joshi RS, Szabo G. Innate immune activation: Parallels in alcohol use disorder and Alzheimer’s disease. Front Mol Neurosci 2022; 15:910298. [PMID: 36157070 PMCID: PMC9505690 DOI: 10.3389/fnmol.2022.910298] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 07/18/2022] [Indexed: 11/16/2022] Open
Abstract
Alcohol use disorder is associated with systemic inflammation and organ dysfunction especially in the liver and the brain. For more than a decade, studies have highlighted alcohol abuse-mediated impairment of brain function and acceleration of neurodegeneration through inflammatory mechanisms that directly involve innate immune cells. Furthermore, recent studies indicate overlapping genetic risk factors between alcohol use and neurodegenerative disorders, specifically regarding the role of innate immunity in the pathomechanisms of both areas. Considering the pressing need for a better understanding of the relevance of alcohol abuse in dementia progression, here we summarize the molecular mechanisms of neuroinflammation observed in alcohol abuse and Alzheimer’s disease, the most common cause of dementia. In addition, we highlight mechanisms that are already established in the field of Alzheimer’s disease that may be relevant to explore in alcoholism to better understand alcohol mediated neurodegeneration and dementia, including the relevance of the liver-brain axis.
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Affiliation(s)
- Adriana Ramos
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
| | - Radhika S. Joshi
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
| | - Gyongyi Szabo
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
- Broad Institute of MIT and Harvard, Cambridge, MA, United States
- *Correspondence: Gyongyi Szabo,
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Suhail M, Sohrab SS, Kamal M, Azhar EI. Role of hepatitis c virus in hepatocellular carcinoma and neurological disorders: an overview. Front Oncol 2022; 12:913231. [PMID: 35965577 PMCID: PMC9372299 DOI: 10.3389/fonc.2022.913231] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 06/28/2022] [Indexed: 11/13/2022] Open
Abstract
The hepatitis C virus (HCV) causes serious issues, affecting 71 million people globally. The most common manifestations range from chronic hepatitis to liver cirrhosis, leading to hepatocellular carcinoma. Many mechanisms are known to play an important role in HCV-induced HCC. The interaction of viral proteins with host cells results in oxidative stress damage, liver inflammation, and irregularities in signaling pathways. These results in the activation of oncogenes and metabolic disturbances, liver fibrosis, and angiogenesis. Additionally, some non-coding RNAs (ncRNAs) and toll-like receptors have been identified and play a significant role in HCC development. This virus is also associated with impairment of the central nervous system, resulting in acute or sub-acute encephalopathy and inflammatory disorders. Neurological disorders are associated with the inflammatory responses of many cells, including microglia and astrocytes. Additionally, there are many other extrahepatic manifestations, including neurological disorders such as depression and fatigue, in 50% of infected patients. These manifestations include neuro-invasion, immune-mediated damage, neurotransmitter alterations, sensory-motor polyneuropathy, sensitivity loss, weakness of the leg, and cryoglobulinemia, which significantly results in a reduced quality of life. HCV infection may be improved using an appropriate diagnosis and direct antiviral therapy for sustained virological response. However, the success of therapy depends on the symptoms and organ damage, diagnosis, and therapeutic strategies applied. Some published reports have discussed that HCV is associated with both HCC and neurological disorders. Additionally, it has also been observed that individuals with HCC also develop neurological disorders compared with individuals with HCV alone. This review aims to provide an overview of the latest information about the relationship between HCV-induced HCC and their role in neurological disorders. Additionally, we have also discussed the progress made in the diagnosis, physio-pathological mechanisms, and strong antiviral therapies developed for HCV infection and HCC, as well as the latest advancements made in the study of the neurological disorders associated with HCV infection.
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Affiliation(s)
- Mohd Suhail
- King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Sayed Sartaj Sohrab
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
- Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
- *Correspondence: Sayed Sartaj Sohrab,
| | - Mohammad Amjad Kamal
- King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
- West China School of Nursing/Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
- Enzymoics Novel Global Community Educational Foundation, Hebersham, NSW, Australia
| | - Esam Ibraheem Azhar
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
- Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
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Cunha LRD, Castro MCMD, Duarte GS, Nascimento GCE, Rocha GA, Silva LD. MAJOR DEPRESSIVE DISORDER IS ASSOCIATED WITH TYPE 2 DIABETES IN PATIENTS WITH CHRONIC HEPATITIS C INFECTION. ARQUIVOS DE GASTROENTEROLOGIA 2021; 58:476-482. [PMID: 34909853 DOI: 10.1590/s0004-2803.202100000-86] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Accepted: 06/11/2021] [Indexed: 11/21/2022]
Abstract
BACKGROUND Major depressive disorder (MDD) is commonly reported in patients with chronic hepatitis C (CHC); however, the factors behind the co-occurrence of these conditions have not been completely clarified yet. OBJECTIVE We aimed to evaluate the frequency of mental disorders in CHC patients and to investigate variables associated with MDD. METHODS CHC patients (n=151) attending a referral Centre for hepatitis were evaluated using the Mini-International Neuropsychiatry Interview and the Cut-Annoyed-Guilty-Eye (CAGE) Questionnaire. Multivariate analysis was used to evaluate independent covariates associated with current MDD. RESULTS Seventy-six (50.3%) patients had, at least, one current psychiatric diagnosis with MDD (33.1%) being the most common. Current MDD was independently associated with age (≤50 yr.) (OR=2.57; 95%CI=1.25-5.29; P=0.01) and type 2 diabetes mellitus (OR=2.80, 95%CI=1.17-6.70; P=0.02). Cirrhosis was associated with type 2 diabetes mellitus (OR=5.09; 95%CI=1.73-15.04; P=0.03) and current alcohol abuse/dependence (OR=2.54; 95%CI=1.04-6.22; P=0.04). DISCUSSION MDD is associated with type 2 diabetes in CHC patients. Even in the direct-acting antivirals (DAAs) era, characterized by great perspectives for the first ample cure of a chronic viral infection, we should ensure that the screening for psychiatric disorders takes place in the course of routine clinical care of patients chronically infected with hepatitis C virus.
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Affiliation(s)
- Luciana Rodrigues da Cunha
- Universidade Federal de Minas Gerais, Faculdade de Medicina, Ambulatório de Hepatites Virais, Instituto Alfa de Gastroenterologia, Belo Horizonte, MG, Brasil.,Universidade Federal de Minas Gerais, Programa de Pós-Graduação em Neurociências, Instituto de Ciências Biológicas, Belo Horizonte, MG, Brasil
| | - Maria Carolina Magalhães de Castro
- Universidade Federal de Minas Gerais, Faculdade de Medicina, Ambulatório de Hepatites Virais, Instituto Alfa de Gastroenterologia, Belo Horizonte, MG, Brasil
| | - Gabriela Silva Duarte
- Universidade Federal de Minas Gerais, Faculdade de Medicina, Ambulatório de Hepatites Virais, Instituto Alfa de Gastroenterologia, Belo Horizonte, MG, Brasil
| | - Graziela Cançado E Nascimento
- Universidade Federal de Minas Gerais, Faculdade de Medicina, Ambulatório de Hepatites Virais, Instituto Alfa de Gastroenterologia, Belo Horizonte, MG, Brasil
| | - Gifone Aguiar Rocha
- Universidade Federal de Minas Gerais, Faculdade de Medicina, Laboratório de Pesquisa em Bacteriologia, Belo Horizonte, MG, Brasil
| | - Luciana Diniz Silva
- Universidade Federal de Minas Gerais, Faculdade de Medicina, Ambulatório de Hepatites Virais, Instituto Alfa de Gastroenterologia, Belo Horizonte, MG, Brasil.,Universidade Federal de Minas Gerais, Faculdade de Medicina, Departamento de Clínica Médica, Belo Horizonte, MG, Brasil
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Santos-Lima C, Souza-Marques B, Vieira F, Isabel Schinoni M, Quarantini LC, Abreu N. Neuropsychological effects of direct-acting antiviral treatment for Hepatitis C virus subjects: A systematic review. J Viral Hepat 2021; 28:1672-1682. [PMID: 34320255 DOI: 10.1111/jvh.13584] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Revised: 06/21/2021] [Accepted: 06/26/2021] [Indexed: 12/15/2022]
Abstract
Direct-acting antivirals (DAAs) have been approved in recent years to treat patients infected by the Hepatitis C virus (HCV). The DAAs treatment is well tolerated and increases sustained virological responses, but there is no consensus about the neuropsychological functioning related to the treatment. This systematic review aims to provide an overview of the recent findings exploring the cognitive effects of DAAs treatment in patients with HCV. After a systematic search on PubMed, Embase, Scopus and LILACS, studies that assessed neuropsychological data related to DAAs treatment were included. We found nine articles, considering the inclusion and exclusion criteria. Three other manuscripts were included after searching for the references listed in the previously mentioned articles. We observed methodological heterogeneity in terms of neuropsychological tests used, cognitive domain explored and the sample characteristic presented between the studies. Studies presented data from HCV subjects monoinfected with or without cirrhosis, advanced liver disease and post-transplant patients; and HCV subjects coinfected with human immunodeficiency virus (HIV). Most results from the 12 studies that explored the effect of DAAs treatment in HCV subjects' neurocognitive functioning demonstrated cognitive improvement following treatment. In general, HCV and HCV/HIV subjects improved processing speed, verbal fluency and verbal/visual episodic memory. The DAAs treatment is effective for neurocognitive functioning in HCV monoinfected and coinfected subjects, with or without advanced liver disease, since neuropsychological scores increased after treatment. Further studies, however, are needed to confirm these findings.
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Affiliation(s)
- Cassio Santos-Lima
- Programa de Pós-graduação em Psicologia, Instituto de Psicologia, Universidade Federal da Bahia, Salvador, Bahia, Brazil.,Laboratório de Pesquisa em Neuropsicologia Clínica e Cognitiva, Instituto de Psicologia, Universidade Federal da Bahia, Salvador, Brazil.,Laboratório de Neuropsicofarmacologia, Serviço de Psiquiatria, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil
| | - Breno Souza-Marques
- Laboratório de Neuropsicofarmacologia, Serviço de Psiquiatria, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil.,Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Brazil
| | - Flávia Vieira
- Laboratório de Neuropsicofarmacologia, Serviço de Psiquiatria, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil.,Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Brazil
| | - Maria Isabel Schinoni
- Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Brazil
| | - Lucas C Quarantini
- Laboratório de Neuropsicofarmacologia, Serviço de Psiquiatria, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil.,Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Brazil
| | - Neander Abreu
- Programa de Pós-graduação em Psicologia, Instituto de Psicologia, Universidade Federal da Bahia, Salvador, Bahia, Brazil.,Laboratório de Pesquisa em Neuropsicologia Clínica e Cognitiva, Instituto de Psicologia, Universidade Federal da Bahia, Salvador, Brazil
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12
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Moretti R, Giuffrè M, Merli N, Caruso P, Di Bella S, Tiribelli C, Crocè LS. Hepatitis C Virus-Related Central and Peripheral Nervous System Disorders. Brain Sci 2021; 11:1569. [PMID: 34942871 PMCID: PMC8699483 DOI: 10.3390/brainsci11121569] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 11/19/2021] [Accepted: 11/23/2021] [Indexed: 12/19/2022] Open
Abstract
Hepatitis C Virus (HCV), despite being a hepatotropic virus, is the causative agent of many systemic disorders, such as vasculitis, autoimmune diseases, lymphoproliferative disorders, and a broad spectrum of neurological and psychiatric manifestations. Although symptoms have been misdiagnosed or underdiagnosed, only recently, evidence of direct (inflammatory) or indirect (immune-mediated) HCV-dependent cerebral effects has been established. HCV infection can promote acute inflammatory response, pro-coagulative status and ischemic disorders, and neurodegeneration. These effects rely on cerebral HCV replication, possibly mediated by blood-brain barrier alterations. Further study is needed to better understand the HCV-related mechanisms of brain damage.
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Affiliation(s)
- Rita Moretti
- Department Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy; (R.M.); (P.C.); (S.D.B.); (L.S.C.)
| | - Mauro Giuffrè
- Department Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy; (R.M.); (P.C.); (S.D.B.); (L.S.C.)
| | - Nicola Merli
- Department Neurological Sciences, University of Ferrara, 44121 Ferrara, Italy;
| | - Paola Caruso
- Department Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy; (R.M.); (P.C.); (S.D.B.); (L.S.C.)
| | - Stefano Di Bella
- Department Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy; (R.M.); (P.C.); (S.D.B.); (L.S.C.)
| | | | - Lory Saveria Crocè
- Department Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy; (R.M.); (P.C.); (S.D.B.); (L.S.C.)
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13
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Kirk FT, Munk DE, Laursen TL, Vilstrup H, Ott P, Grønbæk H, Lauridsen MM, Sandahl TD. Cognitive impairment in stable Wilson disease across phenotype. Metab Brain Dis 2021; 36:2173-2177. [PMID: 34342812 DOI: 10.1007/s11011-021-00804-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Accepted: 07/22/2021] [Indexed: 10/20/2022]
Abstract
In Wilson disease (WD), mutations in the gene encoding the ATP7B copper transport protein causes accumulation of copper especially in liver and brain. WD typically presents with hepatic and/or neuropsychiatric symptoms. Impaired cognition is a well-described feature in patients with neurological WD, while the reports on cognition in hepatic WD patients are fewer and less conclusive. We examined cognition in a cohort of WD patients with both phenotypes. In this cross-sectional pilot study, we investigated cognition in 28 stable Danish WD patients by the PortoSystemic Encephalopathy (PSE) and the Continuous Reaction Time (CRT) tests. Half of the patients were female, and their median age was 35.5 years (IQR 24.5). Their phenotype was hepatic in 14 (50%), neurologic in 10 (36%) and mixed in 4 (14%). The duration of treatment was > 2 year in all patients, and their condition was stable as judged by urinary copper excretion, liver enzymes, and clinical assessment. The hepatic patients did not show signs of liver failure. In total, 16 (57%) patients performed worse than normal in the PSE and/or the CRT tests. The two tests were correlated (rho = 0.60, p = 0.0007), but neither correlated with phenotype, MELD-, Child-Pugh score, 24 h-U-Cu, or treatment type. Measurable cognitive impairment was present in more than half of the stable WD patients independent of phenotype. Thus, our data questions the existence of a purely hepatic phenotype.
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Affiliation(s)
- Frederik Teicher Kirk
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, 8200, Aarhus N, Denmark.
| | - Ditte Emilie Munk
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, 8200, Aarhus N, Denmark
| | - Tea Lund Laursen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, 8200, Aarhus N, Denmark
| | - Hendrik Vilstrup
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, 8200, Aarhus N, Denmark
| | - Peter Ott
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, 8200, Aarhus N, Denmark
| | - Henning Grønbæk
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, 8200, Aarhus N, Denmark
| | - Mette Munk Lauridsen
- Department of Hepatology and Gastroenterology, University Hospital of South Denmark, Esbjerg, Denmark
| | - Thomas Damgaard Sandahl
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, 8200, Aarhus N, Denmark
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14
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Matos ADMB, Dahy FE, de Moura JVL, Marcusso RMN, Gomes ABF, Carvalho FMM, Fernandes GBP, Felix AC, Smid J, Vidal JE, Frota NAF, Casseb J, Easton A, Solomon T, Witkin SS, Malta Romano C, de Oliveira ACP. Subacute Cognitive Impairment in Individuals With Mild and Moderate COVID-19: A Case Series. Front Neurol 2021; 12:678924. [PMID: 34421788 PMCID: PMC8371908 DOI: 10.3389/fneur.2021.678924] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Accepted: 06/30/2021] [Indexed: 11/13/2022] Open
Abstract
Background: Previous reported neurologic sequelae associated with SARS-CoV-2 infection have mainly been confined to hospital-based patients in which viral detection was restricted to nasal/throat swabs or to IgM/IgG peripheral blood serology. Here we describe seven cases from Brazil of outpatients with previous mild or moderate COVID-19 who developed subacute cognitive disturbances. Methods: From June 1 to August 15, 2020, seven individuals 18 to 60 years old, with confirmed mild/moderate COVID-19 and findings consistent with encephalopathy who were observed >7 days after respiratory symptom initiation, were screened for cognitive dysfunction. Paired sera and CSF were tested for SARS-CoV-2 (IgA, IgG ELISA, and RT-PCR). Serum and intrathecal antibody dynamics were evaluated with oligoclonal bands and IgG index. Cognitive dysfunction was assessed by the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and the Clock Drawing Test (CDT). Results: All but one of our patients were female, and the mean age was 42.6 years. Neurologic symptoms were first reported a median of 16 days (IQR 15–33) after initial COVID-19 symptoms. All patients had headache and altered behavior. Cognitive dysfunction was observed mainly in phonemic verbal fluency (MoCA) with a median of six words/min (IQR 5.25–10.75) and altered visuospatial construction with a median of four points (IQR 4–9) (CDT). CSF pleocytosis was not detected, and only one patient was positive for SARS-Co Conclusions: A subacute cognitive syndrome suggestive of SARS-CoV-2-initiated damage to cortico-subcortical associative pathways that could not be attributed solely to inflammation and hypoxia was present in seven individuals with mild/moderate COVID-19.
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Affiliation(s)
| | | | | | | | - Andre Borges Ferreira Gomes
- Hospital Geral de Fortaleza, Serviço de Neurologia, Fortaleza, Brazil.,Programa de Pós-Graduação em Ciências Médicas, Universidade de Fortaleza, Fortaleza, Brazil
| | - Fernanda Martins Maia Carvalho
- Hospital Geral de Fortaleza, Serviço de Neurologia, Fortaleza, Brazil.,Programa de Pós-Graduação em Ciências Médicas, Universidade de Fortaleza, Fortaleza, Brazil
| | | | - Alvina Clara Felix
- Faculdade de Medicina, Instituto de Medicina Tropical, Universidade de São Paulo, São Paulo, Brazil
| | - Jerusa Smid
- Instituto de Infectologia Emilio Ribas, São Paulo, Brazil
| | - Jose Ernesto Vidal
- Faculdade de Medicina, Instituto de Medicina Tropical, Universidade de São Paulo, São Paulo, Brazil.,Instituto de Infectologia Emilio Ribas, São Paulo, Brazil
| | - Norberto Anizio Ferreira Frota
- Hospital Geral de Fortaleza, Serviço de Neurologia, Fortaleza, Brazil.,Programa de Pós-Graduação em Ciências Médicas, Universidade de Fortaleza, Fortaleza, Brazil
| | - Jorge Casseb
- Faculdade de Medicina, Instituto de Medicina Tropical, Universidade de São Paulo, São Paulo, Brazil
| | - Ava Easton
- Encephalitis Society, Malton, United Kingdom.,Department of Clinical Infection, Microbiology and Immunology, University of Liverpool, Liverpool, United Kingdom
| | - Tom Solomon
- National Institute for Health Research Health Protection Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom.,Walton Centre National Health Service Foundation Trust, Liverpool, United Kingdom
| | - Steven S Witkin
- Faculdade de Medicina, Instituto de Medicina Tropical, Universidade de São Paulo, São Paulo, Brazil.,Weill Cornell Medicine, Department of Obstetrics and Gynecology, New York, NY, United States
| | - Camila Malta Romano
- Faculdade de Medicina, Instituto de Medicina Tropical, Universidade de São Paulo, São Paulo, Brazil.,Faculdade de Medicina, Hospital das Clinicas, Universidade de São Paulo, São Paulo, Brazil
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15
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Faccioli J, Nardelli S, Gioia S, Riggio O, Ridola L. Neurological and psychiatric effects of hepatitis C virus infection. World J Gastroenterol 2021; 27:4846-4861. [PMID: 34447230 PMCID: PMC8371503 DOI: 10.3748/wjg.v27.i29.4846] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 05/07/2021] [Accepted: 06/04/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infection is widespread and affects 71 million people worldwide. Although hepatic manifestations are the most frequent, ranging from chronic hepatitis to cirrhosis and hepatocellular carcinoma, it is also associated with several extrahepatic manifestations. Infected patients may present non-specific neurological symptoms, regardless of the presence of liver cirrhosis. Several pathogenetic mechanisms underlying neurological symptoms have been hypothesized: neuroinvasion, immune-mediated damage, neurotransmitter alterations and cryoglobulinemia. Alterations of the central nervous system include cerebral vasculopathy, acute or subacute encephalopathy and inflammatory disorders. HCV infection may be responsible for neuropathies, of which the most frequent form is symmetrical axonal sensory or sensory-motor polyneuropathy which causes loss of leg sensitivity and weakness. Up to 50% of patients with HCV infection may experience cognitive decline and psychological disorders, such as depression and fatigue. HCV associated neurocognitive disorder is independent of the presence of liver cirrhosis and affects different domains than in patients with hepatic encephalopathy. It can be studied using specific tests that mainly explore executive functions, verbal learning and verbal recall. These disorders significantly reduce the quality of life. The new antiviral therapies improve the extrahepatic symptoms of HCV infection and their success depends on the achievement of sustained virological response. However, the effect of therapy may differ depending on the type of organ involved; neurological symptoms can be irreversible if there is organic liver damage. The aim of this review is to provide a critical overview of physiopathological mechanisms, diagnostic and therapeutic strategies of the neurological and psychiatric effects of HCV infection.
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Affiliation(s)
- Jessica Faccioli
- Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome 00185, Italy
| | - Silvia Nardelli
- Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome 00185, Italy
| | - Stefania Gioia
- Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome 00185, Italy
| | - Oliviero Riggio
- Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome 00185, Italy
| | - Lorenzo Ridola
- Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome 00185, Italy
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16
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Walter TJ, Iudicello J, Cookson DR, Franklin D, Tang B, Young JW, Perry W, Ellis R, Heaton RK, Grant I, Minassian A, Letendre S, on behalf of the Translational Methamphetamine AIDS Research Center (TMARC). The Relationships between HIV-1 Infection, History of Methamphetamine Use Disorder, and Soluble Biomarkers in Blood and Cerebrospinal Fluid. Viruses 2021; 13:1287. [PMID: 34372493 PMCID: PMC8310127 DOI: 10.3390/v13071287] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Revised: 06/24/2021] [Accepted: 06/25/2021] [Indexed: 01/13/2023] Open
Abstract
Methamphetamine (METH) use disorder is highly prevalent among people with HIV (PWH) and is a significant public health problem. HIV and METH use are each associated with immune system dysfunction; however, the combined effects on the immune system are poorly understood. This cross-sectional project measured soluble immune biomarkers in plasma and cerebrospinal fluid (CSF) collected from a control group, people with a history of a METH use disorder (METH+), PWH with no history of METH use disorder (HIV+), and PWH with a history of METH use disorder (HIV+/METH+). HIV, METH, and immune dysfunction can also be associated with affective and cognitive deficits, so we characterized mood and cognition in our participants. Two factor analyses were performed for the plasma and CSF biomarkers. Plasma IL-8, Ccl2, VEGF, and 8-isoprostane loaded onto one factor that was highest in the HIV+/METH+ group (p < 0.047) reflecting worse inflammation, vascular injury, and oxidative stress. This plasma factor was also negatively correlated with delayed recall (R = -0.49, p = 0.010), which was worst in the HIV+/METH+ group (p = 0.030 compared to the control group). Overall, these data implicate that combined HIV-1 infection and METH use may exacerbate inflammation, leading to worse cognition.
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Affiliation(s)
- T. Jordan Walter
- Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; (J.I.); (D.R.C.); (D.F.); (B.T.); (J.W.Y.); (W.P.); (R.K.H.); (I.G.); (A.M.)
| | - Jennifer Iudicello
- Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; (J.I.); (D.R.C.); (D.F.); (B.T.); (J.W.Y.); (W.P.); (R.K.H.); (I.G.); (A.M.)
| | - Debra Rosario Cookson
- Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; (J.I.); (D.R.C.); (D.F.); (B.T.); (J.W.Y.); (W.P.); (R.K.H.); (I.G.); (A.M.)
| | - Donald Franklin
- Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; (J.I.); (D.R.C.); (D.F.); (B.T.); (J.W.Y.); (W.P.); (R.K.H.); (I.G.); (A.M.)
| | - Bin Tang
- Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; (J.I.); (D.R.C.); (D.F.); (B.T.); (J.W.Y.); (W.P.); (R.K.H.); (I.G.); (A.M.)
| | - Jared W. Young
- Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; (J.I.); (D.R.C.); (D.F.); (B.T.); (J.W.Y.); (W.P.); (R.K.H.); (I.G.); (A.M.)
| | - William Perry
- Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; (J.I.); (D.R.C.); (D.F.); (B.T.); (J.W.Y.); (W.P.); (R.K.H.); (I.G.); (A.M.)
| | - Ronald Ellis
- Department of Neurosciences, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA;
| | - Robert K. Heaton
- Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; (J.I.); (D.R.C.); (D.F.); (B.T.); (J.W.Y.); (W.P.); (R.K.H.); (I.G.); (A.M.)
| | - Igor Grant
- Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; (J.I.); (D.R.C.); (D.F.); (B.T.); (J.W.Y.); (W.P.); (R.K.H.); (I.G.); (A.M.)
| | - Arpi Minassian
- Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; (J.I.); (D.R.C.); (D.F.); (B.T.); (J.W.Y.); (W.P.); (R.K.H.); (I.G.); (A.M.)
- VA Center of Excellence for Stress and Mental Health, Veterans Administration San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161, USA
| | - Scott Letendre
- Division of Infectious Disease and Global Public Health, Department of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
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17
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Patients with Hepatitis C Infection and Normal Liver Function: A Neuropsychological and Neurophysiological Assessment of Cognitive Functions. Int J Hepatol 2021; 2021:8823676. [PMID: 34113467 PMCID: PMC8154309 DOI: 10.1155/2021/8823676] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Revised: 04/21/2021] [Accepted: 05/10/2021] [Indexed: 12/11/2022] Open
Abstract
Several studies have proposed a link between chronic hepatitis C virus (HCV) infection and the development of cognitive disorders. However, the inclusion of confounding factors in their samples significantly limits the interpretation of the results. Therefore, here, we aimed to compare the neurophysiological and cognitive performance between patients with HCV infection and a control group after excluding other factors that may cause cognitive impairment. This cross-sectional, group-control, observational study was performed from September 12, 2014, to October 20, 2017. HCV-infected patients and healthy individuals between 18 and 77 years were considered eligible. The exclusion criteria included well-established causes of cognitive impairment, such as depression and cirrhosis. The participants were submitted to neuropsychological testing to evaluate global cognitive function (minimental), sustained attention, divided attention, selective attention, working memory, psychomotor speed, and executive function and to a neurophysiological evaluation using quantitative electroencephalograms and P300 cognitive evoked potentials. Among the 309 patients considered eligible for the study, we excluded 259 patients who had one or more characteristics from the preestablished exclusion criteria, 18 who did not undergo neuropsychological and neurophysiological testing, and five who exhibited depression. The final sample consisted of 27 patients each in the HCV and control groups. The groups did not differ in age, schooling, and sex. The patients in the HCV group exhibited poorer performances in the cognitive areas involving attention (p = 0.01), memory (p = 0.02), and psychomotor velocity (p = 0.04) apart from exhibiting prolonged latency in the P3b component (p = 0.03) and Z score (p = 0.02) of the P300 evoked cognitive potential. In this study performed with strict selection criteria, on conducting neuropsychological and neurophysiological evaluations, we detected the presence of cognitive impairment characterized by the involvement of attention, working memory, psychomotor processing speed, and memory in the HCV group.
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18
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O'Gorman P, Strahan O, Ferguson D, Monaghan A, Kennedy M, Forde C, Melo AM, Doherty DG, O'Brien KK, McKiernan S, Kenny RA, Coen R, Doherty C, Bergin C, Gormley J, Norris S. Improvement in cognitive impairment following a 12-week aerobic exercise intervention in individuals with non-cirrhotic chronic hepatitis C. J Viral Hepat 2021; 28:637-650. [PMID: 33372320 DOI: 10.1111/jvh.13460] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Revised: 10/02/2020] [Accepted: 11/09/2020] [Indexed: 12/09/2022]
Abstract
Cognitive impairment occurs in 30%-50% of patients with non-cirrhotic chronic hepatitis C virus (HCV) infection. Exercise is beneficial in preventing and treating cognitive impairment and cardiometabolic abnormalities in many chronic inflammatory diseases, but there are few studies investigating the impact of exercise in HCV infection. The study aimed to assess the effect of a 12-week aerobic exercise intervention on cognition and extrahepatic manifestations in individuals with HCV. In this nonrandomized controlled pilot study, individuals with HCV participated in a 12-week aerobic exercise intervention. Outcome measures included cognition (Montreal Cognitive Assessment [MOCA], Trail Making Test A & B [TMT-A; TMT-B], Digit Symbol Test [DST]), cardiorespiratory fitness (estimated V ˙ O 2 max ), physical activity (accelerometry), anthropometry, quality of life (depression; fatigue; sleep quality) and biochemical markers. Outcomes were assessed at baseline (T0), intervention completion (T1) and 12 weeks after intervention completion (T2). Thirty-one patients completed the study (exercise group n = 13, control group n = 18). In the exercise group, cognition improved at T1 in the TMT-A (31% mean improvement, p = 0.019), TMT-B (15% mean improvement, p = 0.012) time and MOCA (14% mean improvement, p ≤ 0.001). These improvements were not maintained at T2. Depression (p = 0.038), sleep quality (p = 0.002), fatigue (p = 0.037) and estimated V ˙ O 2 max (7.8 mL kg-1 min-1 [22%] mean increase, p = 0.004) also improved at T1. In conclusion, this study demonstrates the benefits of a 12-week aerobic exercise intervention in improving cognition, quality of life and cardiorespiratory fitness in individuals with HCV. Larger studies are needed to confirm these findings and strategies for continued exercise engagement in individuals with HCV are warranted for sustained benefits.
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Affiliation(s)
- Philip O'Gorman
- Discipline of Physiotherapy, Trinity College, The University of Dublin, Dublin, Ireland
| | - Orla Strahan
- School of Psychology, Trinity College, The University of Dublin, Dublin, Ireland
| | - Damien Ferguson
- Academic Unit of Neurology, Trinity College, The University of Dublin, Dublin, Ireland
- Department of Neurology, St James's Hospital, Dublin, Ireland
| | - Ann Monaghan
- Discipline of Physiotherapy, Trinity College, The University of Dublin, Dublin, Ireland
| | - Megan Kennedy
- Discipline of Physiotherapy, Trinity College, The University of Dublin, Dublin, Ireland
| | - Cuisle Forde
- Discipline of Physiotherapy, Trinity College, The University of Dublin, Dublin, Ireland
| | - Ashanty M Melo
- Discipline of Immunology, Trinity College, The University of Dublin, Dublin, Ireland
| | - Derek G Doherty
- Discipline of Immunology, Trinity College, The University of Dublin, Dublin, Ireland
| | - Kelly K O'Brien
- Department of Physical Therapy, University of Toronto, Toronto, ON, Canada
- Institute of Health Policy, Management and Evaluation (IHPME), University of Toronto, Toronto, ON, Canada
- Rehabilitation Sciences Institute (RSI), University of Toronto, Toronto, ON, Canada
| | - Susan McKiernan
- Department of Clinical Medicine, Trinity College, The University of Dublin, Dublin, Ireland
- Department of Hepatology, St James's Hospital, Dublin, Ireland
| | - Rose Anne Kenny
- The Irish Longitudinal Study on Ageing (TILDA), Trinity College, The University of Dublin, Dublin, Ireland
- Mercer's Institute for Successful Ageing, St James's Hospital, Dublin, Ireland
| | - Robert Coen
- Mercer's Institute for Successful Ageing, St James's Hospital, Dublin, Ireland
| | - Colin Doherty
- Academic Unit of Neurology, Trinity College, The University of Dublin, Dublin, Ireland
- Department of Neurology, St James's Hospital, Dublin, Ireland
- FutureNeuro Centre for Rare and Chronic Diseases, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Colm Bergin
- Department of Clinical Medicine, Trinity College, The University of Dublin, Dublin, Ireland
- Department of Genito-Urinary Medicine and Infectious Diseases, St James's Hospital, Dublin, Ireland
| | - John Gormley
- Discipline of Physiotherapy, Trinity College, The University of Dublin, Dublin, Ireland
| | - Suzanne Norris
- Department of Clinical Medicine, Trinity College, The University of Dublin, Dublin, Ireland
- Department of Hepatology, St James's Hospital, Dublin, Ireland
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Ihle A, Gouveia ÉR, Gouveia BR, Haas M, Zuber S, Orsholits D, Cheval B, Sieber S, Cullati S, Kliegel M. Cognitive Reserve Mitigates Decline in Executive Functioning Following Hepatobiliary Diseases. SWISS JOURNAL OF PSYCHOLOGY 2020. [DOI: 10.1024/1421-0185/a000237] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Abstract. The cognitive reserve hypothesis postulates that lifelong cognitive stimulation establishes a buffer that is instrumental in maintaining cognitive health. To examine this conceptual proposition in detail, we applied a novel, more general conceptual view that included recent models of vulnerability and examined whether the longitudinal association between hepatobiliary diseases and later decline in executive functioning across 6 years varied by cognitive reserve. For this purpose, we investigated longitudinal data from 897 older individuals ( M = 74.33 years) tested using the Trail Making Test (TMT) in two waves 6 years apart. Individuals reported information on key commonly used indicators of lifelong cognitive reserve build-up (i.e., education, work, and participation in leisure activity) and hepatobiliary diseases. The results revealed a significant interaction of hepatobiliary diseases with participation in leisure activity on latent change in executive functioning. Specifically, only in individuals with little (but not greater) participation in leisure activity did hepatobiliary diseases significantly predict a steeper decline in executive functioning over 6 years (i.e., increases in TMT finishing time). In conclusion, the unfavorable aftereffects of hepatobiliary diseases on a later decline in executive functioning seem to be mitigated in individuals who have built up greater cognitive reserve via participation in leisure activity during their life.
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Affiliation(s)
- Andreas Ihle
- Cognitive Aging Lab, Department of Psychology, University of Geneva, Geneva, Switzerland
- Center for the Interdisciplinary Study of Gerontology and Vulnerability, University of Geneva, Geneva, Switzerland
- Swiss National Centre of Competence in Research LIVES – Overcoming Vulnerability: Life Course Perspectives, Lausanne and Geneva, Switzerland
| | - Élvio R. Gouveia
- Center for the Interdisciplinary Study of Gerontology and Vulnerability, University of Geneva, Geneva, Switzerland
- Department of Physical Education and Sport, University of Madeira, Funchal, Portugal
- LARSyS, Interactive Technologies Institute, Funchal, Portugal
| | - Bruna R. Gouveia
- Center for the Interdisciplinary Study of Gerontology and Vulnerability, University of Geneva, Geneva, Switzerland
- LARSyS, Interactive Technologies Institute, Funchal, Portugal
- Health Administration Institute, Secretary of Health of the Autonomous Region of Madeira, Funchal, Portugal
- Saint Joseph of Cluny Higher School of Nursing, Funchal, Portugal
| | - Maximilian Haas
- Cognitive Aging Lab, Department of Psychology, University of Geneva, Geneva, Switzerland
- Center for the Interdisciplinary Study of Gerontology and Vulnerability, University of Geneva, Geneva, Switzerland
| | - Sascha Zuber
- Cognitive Aging Lab, Department of Psychology, University of Geneva, Geneva, Switzerland
- Center for the Interdisciplinary Study of Gerontology and Vulnerability, University of Geneva, Geneva, Switzerland
- Swiss National Centre of Competence in Research LIVES – Overcoming Vulnerability: Life Course Perspectives, Lausanne and Geneva, Switzerland
| | - Dan Orsholits
- Center for the Interdisciplinary Study of Gerontology and Vulnerability, University of Geneva, Geneva, Switzerland
- Swiss National Centre of Competence in Research LIVES – Overcoming Vulnerability: Life Course Perspectives, Lausanne and Geneva, Switzerland
| | - Boris Cheval
- Swiss Center for Affective Sciences, University of Geneva, Geneva, Switzerland
- Laboratory for the Study of Emotion Elicitation and Expression (E3Lab), Department of Psychology, University of Geneva, Geneva, Switzerland
| | - Stefan Sieber
- Swiss National Centre of Competence in Research LIVES – Overcoming Vulnerability: Life Course Perspectives, Lausanne and Geneva, Switzerland
- Institute of Demography and Socioeconomics, University of Geneva, Geneva, Switzerland
| | - Stéphane Cullati
- Population Health Laboratory, Department of Community Health, University of Fribourg, Fribourg, Switzerland
- Quality of Care Service, Department of Readaptation and Geriatrics, University of Geneva, Geneva, Switzerland
| | - Matthias Kliegel
- Cognitive Aging Lab, Department of Psychology, University of Geneva, Geneva, Switzerland
- Center for the Interdisciplinary Study of Gerontology and Vulnerability, University of Geneva, Geneva, Switzerland
- Swiss National Centre of Competence in Research LIVES – Overcoming Vulnerability: Life Course Perspectives, Lausanne and Geneva, Switzerland
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Gascon MRP, Benute GRG, Macedo EC, CapitÃo CG, Vidal JE, Smid J, Marcusso RMN, Lucia MCSD, Penalva-DE-Oliveira AC, Diament D. Cognitive assessment in patients with Hepatitis C submitted to treatment with Sofosbuvir and Simeprevir or Daclatasvir. ARQUIVOS DE NEURO-PSIQUIATRIA 2020; 78:342-348. [PMID: 32609193 DOI: 10.1590/0004-282x20200022] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Received: 02/02/2020] [Accepted: 02/06/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND Hepatitis C can be defined as an infectious disease that develops an inflammatory activity, which may cause an impairment in the central nervous system, may cause cognitive impairments and symptoms of depression. OBJECTIVE The objective of this study was to verify the cognitive performance of patients with chronic hepatitis C before and after treatment with simeprevir, sofosbuvir, and daclatasvir. METHODS A prospective study was carried out in three stages: before, right after treatment, and six months after. Fifty-eight patients under clinical follow-up were evaluated at the Emílio Ribas Infectology Institute, in São Paulo, Brazil. The following instruments were used: sociodemographic questionnaire, Lawton's Scale, Beck's Depression Inventory, and a battery of neuropsychological tests that evaluated: intellectual function, memory, attention, executive function, and motor and processing speed). For statistical analysis, the analyses described (mean, frequency, and standard deviation), chi-square, and ANOVA were used. RESULTS Most of the participants were male (n=30, 51.7%), with a mean of 58.23±8.79 years, mean schooling of 9.75±4.43 years. Comparing the results of neuropsychological evaluations (before, just after completion of drugs, and six months), a significant improvement was observed in relation to the acquisition of new knowledge (p=0.03), late visual memory (p=0.01), and tendency towards alternate attention (p=0.07). CONCLUSION The treatment of the hepatitis C virus improved cognitive performance, especially in relation to memory.
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Affiliation(s)
- Maria Rita Polo Gascon
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento: Divisão de Psicologia, São Paulo SP, Brazil
| | - Glaucia Rosana Guerra Benute
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Cliníca de Obstetricia - Pós-Graduação, São Paulo SP, Brazil
| | | | - Claudio Garcia CapitÃo
- Instituto de Infectologia Emilio Ribas, Departamento de Psicologia, São Paulo SP, Brazil
| | - José Ernesto Vidal
- Universidade de São Paulo, Faculdade de Medicina da USP, Departamento de Moléstias Infecciosas e Parasitárias, São Paulo SP, Brazil.,Instituto de Infectologia Emilio Ribas, Departamento de Neurologia, São Paulo SP, Brazil
| | - Jerusa Smid
- Instituto de Infectologia Emilio Ribas, Departamento de Neurologia, São Paulo SP, Brazil
| | | | | | | | - Decio Diament
- Instituto de Infectologia Emilio Ribas, Departamento de Doenças Infecciosas, Grupo de Hepatites, São Paulo SP, Brazil
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Catania VE, Malaguarnera G, Fiorenza G, Chisari EM, Lipari AR, Gallina V, Pennisi M, Lanza G, Malaguarnera M. Hepatitis C Virus Infection Increases Fatigue in Health Care Workers. Diseases 2020; 8:37. [PMID: 33076215 PMCID: PMC7709099 DOI: 10.3390/diseases8040037] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Revised: 10/04/2020] [Accepted: 10/12/2020] [Indexed: 02/07/2023] Open
Abstract
Fatigue is a common state associated with a weakening or depletion of one's physical and mental resources, that leads to the inability to continue the individual functioning at a normal level of activity. Frequently, fatigue represents a response to infections, inflammation and autoimmune diseases. The scope of this study was to evaluate the fatigue in healthcare workers with and without hepatitis C virus (HCV) infection. Mental, physical and severity fatigue were evaluated through Krupp, Wessely and Powell fatigue scale. Anti-HCV antibodies, HCV RNA and HCV genotypes were also measured. Physical, mental and severity fatigue were higher in healthcare workers with HCV infection than the healthcare workers without infection (p < 0.01). Our data showed a direct link between fatigue and HCV infection in healthcare workers. Further studies are needed to evaluate HCV antiviral treatments on fatigue severity and on quality of life in healthcare workers.
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Affiliation(s)
- Vito Emanuele Catania
- Department of Medical, Surgical Sciences and Advanced Technologies “G.F. Ingrassia”, University of Catania, 95124 Catania, Italy;
| | - Giulia Malaguarnera
- “The Great Senescence” Research Centre, University of Catania, 95100 Catania, Italy; (G.M.); (G.F.)
| | - Giorgia Fiorenza
- “The Great Senescence” Research Centre, University of Catania, 95100 Catania, Italy; (G.M.); (G.F.)
| | | | | | - Valentino Gallina
- SPRESAL ASP ENNA, 94100 Enna, Italy; (A.R.L.); (V.G.)
- Faculty of Engineering and Architecture-Risk analysis and work safety organization-Kore University of Enna, 94100 Enna, Italy
| | - Manuela Pennisi
- Department of Biomedical and Biotechnological Science, University of Catania, 95123 Catania, Italy;
| | - Giuseppe Lanza
- Department of Surgery and Medical-Surgical Specialties, University of Catania, 95123 Catania, Italy;
| | - Michele Malaguarnera
- “The Great Senescence” Research Centre, University of Catania, 95100 Catania, Italy; (G.M.); (G.F.)
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22
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Fernández-Bargiela N, Rotea-Salvo S, Margusino-Framiñán L, Balboa-Barreiro V, Martín-Herranz I, Castro-Iglesias Á, Mena-De-Cea Á, López-Calvo S, Vázquez-Rodríguez P, Míguez-Rey E, Cid-Silva P. Discontinuation due to neuropsychiatric adverse events with efavirenz- and dolutegravir-based antiretroviral therapy: a comparative real-life study. Eur J Hosp Pharm 2020; 29:207-211. [PMID: 33051194 DOI: 10.1136/ejhpharm-2020-002374] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 07/19/2020] [Accepted: 08/18/2020] [Indexed: 11/04/2022] Open
Abstract
OBJECTIVES Despite the high efficacy of antiretroviral treatment, no drug is free from adverse events (AEs). Efavirenz (EFV) and dolutegravir (DTG) are antiretroviral drugs for which neuropsychiatric adverse events (NPAEs) have been described. This study evaluated the safety and tolerability of DTG-based and EFV-based antiretroviral regimens in HIV-infected patients. METHODS A retrospective observational study was carried out in HIV-infected patients who started DTG- or EFV-based antiretroviral treatment from January 2008 to December 2018 at a reference hospital in north-western Spain. Epidemiological, clinical and immunovirological data were recorded. A statistical analysis was performed with SPSS software. RESULTS A total of 282 DTG- and 148 EFV-based therapies were initiated. During follow-up, statistically significant differences have been found between the rate of patients who discontinued DTG and EFV due to AEs (12.1% vs 35.8%, p<0.001) and the main AEs in both groups, NPAEs (8.2% vs 25.0%, p<0.001). Female gender (OR 2.610 (95% CI 1.327 to 5.133), p=0.005) was associated with discontinuations due to AEs. Patients with documented psychiatric disorders were at higher risk of discontinuation due to NPAEs (OR 4.782 (95% CI 1.190 to 19.220), p=0.027). The multivariate analysis showed a 61.2% risk reduction in benzodiazepine prescriptions in patients treated with DTG. In both groups, patients needed consultation and follow-up in the psychiatry unit (16.9% in the EFV group and 8.9% in the DTG group, p=0.021). CONCLUSIONS We found a high rate of discontinuations due to AEs and NPAEs, prescription of benzodiazepines and a requirement for consultation in a psychiatric unit in both treatment groups, especially with EFV.
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Affiliation(s)
| | - Sandra Rotea-Salvo
- Service of Pharmacy, Universitary Hospital of A Coruña (CHUAC), SERGAS, A Coruña, Spain
| | - Luis Margusino-Framiñán
- Service of Pharmacy, Universitary Hospital of A Coruña (CHUAC), SERGAS, A Coruña, Spain.,Division of Clinical Virology, Biomedical Research Institute of A Coruña (INIBIC), University Hospital of A Coruña (CHUAC), SERGAS, Universitary of A Coruña, A Coruña, Spain
| | - Vanesa Balboa-Barreiro
- Clinical Epidemiology and Biostatistics Unit, Biomedical Research Institute of A Coruña (INIBIC), Universitary Hospital of A Coruña (CHUAC), SERGAS, Universitary of A Coruña (UDC), A Coruña, Spain
| | - Isabel Martín-Herranz
- Service of Pharmacy, Universitary Hospital of A Coruña (CHUAC), SERGAS, A Coruña, Spain
| | - Ángeles Castro-Iglesias
- Division of Clinical Virology, Biomedical Research Institute of A Coruña (INIBIC), University Hospital of A Coruña (CHUAC), SERGAS, Universitary of A Coruña, A Coruña, Spain.,Service of Infectious Internal Medicine, Universitary Hospital of A Coruña (CHUAC), SERGAS, A Coruña, Spain
| | - Álvaro Mena-De-Cea
- Division of Clinical Virology, Biomedical Research Institute of A Coruña (INIBIC), University Hospital of A Coruña (CHUAC), SERGAS, Universitary of A Coruña, A Coruña, Spain.,Service of Infectious Internal Medicine, Universitary Hospital of A Coruña (CHUAC), SERGAS, A Coruña, Spain
| | - Soledad López-Calvo
- Division of Clinical Virology, Biomedical Research Institute of A Coruña (INIBIC), University Hospital of A Coruña (CHUAC), SERGAS, Universitary of A Coruña, A Coruña, Spain.,Service of Infectious Internal Medicine, Universitary Hospital of A Coruña (CHUAC), SERGAS, A Coruña, Spain
| | - Pilar Vázquez-Rodríguez
- Division of Clinical Virology, Biomedical Research Institute of A Coruña (INIBIC), University Hospital of A Coruña (CHUAC), SERGAS, Universitary of A Coruña, A Coruña, Spain.,Service of Infectious Internal Medicine, Universitary Hospital of A Coruña (CHUAC), SERGAS, A Coruña, Spain
| | - Enrique Míguez-Rey
- Division of Clinical Virology, Biomedical Research Institute of A Coruña (INIBIC), University Hospital of A Coruña (CHUAC), SERGAS, Universitary of A Coruña, A Coruña, Spain.,Service of Infectious Internal Medicine, Universitary Hospital of A Coruña (CHUAC), SERGAS, A Coruña, Spain
| | - Purificación Cid-Silva
- Service of Pharmacy, Universitary Hospital of A Coruña (CHUAC), SERGAS, A Coruña, Spain .,Division of Clinical Virology, Biomedical Research Institute of A Coruña (INIBIC), University Hospital of A Coruña (CHUAC), SERGAS, Universitary of A Coruña, A Coruña, Spain
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23
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Pocuca N, Young JW, MacQueen DA, Letendre S, Heaton RK, Geyer MA, Perry W, Grant I, Minassian A. Sustained attention and vigilance deficits associated with HIV and a history of methamphetamine dependence. Drug Alcohol Depend 2020; 215:108245. [PMID: 32871507 PMCID: PMC7811354 DOI: 10.1016/j.drugalcdep.2020.108245] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2020] [Revised: 07/31/2020] [Accepted: 08/16/2020] [Indexed: 12/22/2022]
Abstract
BACKGROUND Human immunodeficiency virus (HIV)-associated neurocognitive disorders persist in the era of antiretroviral therapy. One factor that is elevated among persons with HIV (PWH) and independently associated with neurocognitive impairment is methamphetamine dependence (METH). Such dependence may further increase cognitive impairment among PWH, by delaying HIV diagnosis (and thus, antiretroviral therapy initiation), which has been posited to account for persistent cognitive impairment among PWH, despite subsequent treatment-related viral load suppression (VLS; <50 copies of the virus per milliliter in plasma or cerebrospinal fluid). This study examined the main and interactive (additive versus synergistic) effects of HIV and history of METH on the sustained attention and vigilance cognitive domain, while controlling for VLS. METHODS Participants included 205 (median age = 44 years; 77% males; HIV-/METH- n = 67; HIV+/METH - n = 49; HIV-/METH+ n = 36; HIV+/METH+ n = 53) individuals enrolled in the Translational Methamphetamine AIDS Research Center, who completed Conners' and the 5-Choice continuous performance tests (CPTs). RESULTS METH participants exhibited deficits in sustained attention and vigilance; however, these effects were not significant after excluding participants who had a positive urine toxicology screen for methamphetamine. Controlling for VLS, PWH did not have worse sustained attention and vigilance, but consistently displayed slower reaction times across blocks, relative to HIV- participants. There was no HIV x METH interaction on sustained attention and vigilance. CONCLUSIONS Recent methamphetamine use among METH people and detectable viral loads are detrimental to sustained attention and vigilance. These findings highlight the need for prompt diagnosis of HIV and initiation of antiretroviral therapy, and METH use interventions.
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Affiliation(s)
- Nina Pocuca
- Department of Psychiatry, University of California San Diego, 9500 Gilman Drive MC 0804, La Jolla, CA, 92093-0804, United States.
| | - Jared W Young
- Department of Psychiatry, University of California San Diego, 9500 Gilman Drive MC 0804, La Jolla, CA, 92093-0804, United States; Desert-Pacific Mental Illness Research Education and Clinical Center, VA San Diego Healthcare System, San Diego, CA, United States
| | - David A MacQueen
- Department of Psychiatry, University of California San Diego, 9500 Gilman Drive MC 0804, La Jolla, CA, 92093-0804, United States; Desert-Pacific Mental Illness Research Education and Clinical Center, VA San Diego Healthcare System, San Diego, CA, United States
| | - Scott Letendre
- Department of Psychiatry, University of California San Diego, 9500 Gilman Drive MC 0804, La Jolla, CA, 92093-0804, United States
| | - Robert K Heaton
- Department of Psychiatry, University of California San Diego, 9500 Gilman Drive MC 0804, La Jolla, CA, 92093-0804, United States
| | - Mark A Geyer
- Department of Psychiatry, University of California San Diego, 9500 Gilman Drive MC 0804, La Jolla, CA, 92093-0804, United States; Desert-Pacific Mental Illness Research Education and Clinical Center, VA San Diego Healthcare System, San Diego, CA, United States
| | - William Perry
- Department of Psychiatry, University of California San Diego, 9500 Gilman Drive MC 0804, La Jolla, CA, 92093-0804, United States
| | - Igor Grant
- Department of Psychiatry, University of California San Diego, 9500 Gilman Drive MC 0804, La Jolla, CA, 92093-0804, United States
| | - Arpi Minassian
- Department of Psychiatry, University of California San Diego, 9500 Gilman Drive MC 0804, La Jolla, CA, 92093-0804, United States; VA Center of Excellence for Stress and Mental Health, Veterans Administration San Diego HealthCare System, 3350 La Jolla Village Drive, San Diego, CA, 92161, United States
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Abstract
PURPOSE OF REVIEW Liver transplantation (LT) remains the only way to cure patients with severe liver diseases. Important questions about neurological sequelae and quality of life after LT have emerged. In this review, we discuss the neurocognitive changes associated with LT and we conclude with recommendations in this regard for patients, caregivers, and physicians. RECENT FINDINGS Compared with other solid organ recipients, LT patients tend to have a higher incidence (up to 30%) of neurological complications post-LT. Even in absence of previous episodes of hepatic encephalopathy (HE), some patients display new onset of neurological symptoms post-LT, raising the concern about the role of other factors that may have a direct impact on cognitive function. SUMMARY Different mechanisms have been postulated to explain these postoperative neurological symptoms. They include sequelae of HE, persistent impairment of cognitive function due to cirrhosis, or postoperative decompensation of an unknown or undiagnosed neurodegenerative disorder.
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Affiliation(s)
- Somaya A. M. Albhaisi
- Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298-0341 USA
| | - Jasmohan S. Bajaj
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University and McGuire VA Medical Center, 1201 Broad Rock Boulevard, Richmond, VA USA
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Cognitive impairment severity in relation to signs of subclinical Wernicke's encephalopathy in HIV and alcoholism comorbidity. AIDS 2020; 34:391-403. [PMID: 31725430 PMCID: PMC7021228 DOI: 10.1097/qad.0000000000002428] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES The comorbidity of HIV infection and alcoholism (ALC) is prevalent. Wernicke's encephalopathy, a neurological disorder resulting from thiamine depletion, has been generally associated with alcoholism but has also been reported in HIV infection. This study examined whether subclinical Wernicke's encephalopathy signs could contribute to the heterogeneity of cognitive and motor deficits observed in individuals with both disease conditions (HIV+ALC). DESIGN Sixty-one HIV+ALC individuals and 59 controls were assessed on attention and working memory, production, immediate and delayed episodic memory, visuospatial abilities, and upper limb motor function. METHODS Using Caine criteria (dietary deficiency, oculomotor abnormality, cerebellar dysfunction, and altered mental state), HIV+ALC individuals were classified by subclinical Wernicke's encephalopathy risk factors. RESULTS Signs of subclinical Wernicke's encephalopathy were present in 20% of the HIV+ALC participants. For attention/working memory, delayed memory, and upper limb motor function, HIV+ALC Caine 2+ (i.e. meeting two or three criteria) demonstrated the most severe deficits, scoring lower than HIV+ALC Caine 1 (i.e. meeting one criterion), HIV+ALC Caine 0 (i.e. meeting no criteria), and controls. CONCLUSION The high prevalence of subclinical signs of Wernicke's encephalopathy and relevance to performance indicate that this condition should be considered in assessment of HIV-infected individuals, especially when alcoholism comorbidity is known or suspected. Above and beyond clinical factors, such as depression, alcoholism and HIV disease-related variables, AIDS, hepatitis C and drug history known to mediate neuropsychological performance, subclinical Wernicke's encephalopathy signs could partly explain the heterogeneity in patterns and severity of cognitive and motor impairments in HIV-infected individuals with alcoholism comorbidity.
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26
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Cognitive and Motor Impairment Severity Related to Signs of Subclinical Wernicke's Encephalopathy in HIV Infection. J Acquir Immune Defic Syndr 2020; 81:345-354. [PMID: 30958387 DOI: 10.1097/qai.0000000000002043] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Wernicke's encephalopathy (WE) is a neurological condition resulting from thiamine deficiency. Although commonly associated with alcoholism, nonalcoholic WE has been described in individuals with HIV infection, but subclinical WE may be underdiagnosed. The current study questioned whether the presence of subclinical WE signs underlies cognitive and motor deficits in HIV individuals as observed in alcoholism. SETTING Fifty-six HIV-positive individuals (HIV+) and 53 HIV-negative controls (HIV-) were assessed on 6 cognitive and motor domains: attention/working memory, production, immediate and delayed episodic memory, visuospatial abilities, and upper-limb motor function. METHODS Based on a rating scheme by Caine et al, HIV+ individuals were categorized by subclinical WE risk factors (dietary deficiency, oculomotor abnormality, cerebellar dysfunction, and altered mental state). Performance was expressed as age- and education-corrected Z-scores standardized on controls. RESULTS Sorting by Caine criteria yielded 20 HIV+ as Caine 0 (ie, meeting no criteria), 22 as Caine 1 (ie, meeting one criterion), and 14 as Caine 2 (ie, meeting 2 criteria). Comparison among HIV+ Caine subgroups revealed a graded effect: Caine 0 performed at control levels, Caine 1 showed mild to moderate deficits on some domains, and Caine 2 showed the most severe deficits on each domain. CONCLUSION This graded severity pattern of performance among Caine subgroups suggests that signs of subclinical WE can partly explain the heterogeneity in HIV-related cognitive and motor impairment. This study highlights the utility of Caine criteria in identifying potential causes of HIV-related neurocognitive disorders and has implications for disease management.
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27
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Waclawik K, Jones AA, Barbic SP, Gicas KM, O'Connor TA, Smith GN, Leonova O, Mathias S, Barr AM, Procyshyn RM, Lang DJ, Woodward ML, MacEwan GW, Panenka WJ, Yamamoto A, Honer WG, Thornton AE. Cognitive Impairment in Marginally Housed Youth: Prevalence and Risk Factors. Front Public Health 2019; 7:270. [PMID: 31649909 PMCID: PMC6792471 DOI: 10.3389/fpubh.2019.00270] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Accepted: 09/09/2019] [Indexed: 11/30/2022] Open
Abstract
Objective: Homeless and marginally housed youth are particularly vulnerable members of society, and are known to experience numerous health problems, including psychiatric illness, substance use, and viral infection. Despite the presence of these risk factors for cognitive compromise, there is limited research on the cognitive functioning of homeless and marginally housed youth. The present study examines the degree and pattern of cognitive impairment and associations with key risk factors in a sample of marginally housed young adults. Method: Participants (N = 101) aged 20-29 years old were recruited from single-room occupancy hotels, and underwent cognitive, psychiatric, neurological, and serological assessments. Results: Forty percent of participants were identified as mildly cognitively impaired across multiple domains, and 16% were moderately-severely impaired. Deficits in memory and attention were most prevalent, while impairments in inhibitory control/processing speed and cognitive flexibility were also present but tended to be less severe. Developmental and historical factors (premorbid intellectual functioning, neurological soft signs, earlier exposure to and longer duration of homelessness or marginal housing), as well as current health risks (stimulant dependence and hepatitis C exposure), were associated with cognitive impairment. Conclusions: The strikingly high rate of cognitive impairment in marginally housed young adults represents a major public health concern and is likely to pose a significant barrier to treatment and rehabilitation. These results suggest that the pathway to cognitive impairment involves both developmental vulnerability and modifiable risk factors. This study highlights the need for early interventions that address cognitive impairment and risk factors in marginalized young people.
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Affiliation(s)
- Kristina Waclawik
- Department of Psychology, Simon Fraser University, Burnaby, BC, Canada
| | - Andrea A. Jones
- Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
| | - Skye P. Barbic
- Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
- Department of Occupational Science and Occupational Therapy, University of British Columbia, Vancouver, BC, Canada
- Centre for Health Evaluation and Outcome Sciences, Vancouver, BC, Canada
- Providence Health Care and Foundry, Vancouver, BC, Canada
| | - Kristina M. Gicas
- Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
| | | | - Geoffrey N. Smith
- Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
| | - Olga Leonova
- Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
| | - Steve Mathias
- Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
- Centre for Health Evaluation and Outcome Sciences, Vancouver, BC, Canada
- Providence Health Care and Foundry, Vancouver, BC, Canada
- St. Paul's Hospital, Vancouver, BC, Canada
| | - Alasdair M. Barr
- Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC, Canada
| | - Ric M. Procyshyn
- Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
| | - Donna J. Lang
- Department of Radiology, University of British Columbia, Vancouver, BC, Canada
| | - Melissa L. Woodward
- Department of Radiology, University of British Columbia, Vancouver, BC, Canada
| | - G. William MacEwan
- Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
- St. Paul's Hospital, Vancouver, BC, Canada
| | - William J. Panenka
- Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
| | | | - William G. Honer
- Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
| | - Allen E. Thornton
- Department of Psychology, Simon Fraser University, Burnaby, BC, Canada
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Weinstein AA, Estep JM, de Avila L, Curry M, Golabi P, Escheik C, Birerdinc A, Stepanova M, Price JK, Gerber L, Younossi ZM. Relationships among neurotransmitters, cytokines and cognitive performance for individuals with hepatitis C achieving sustained virologic response: A pilot study. J Neuroimmunol 2019; 335:577022. [PMID: 31445380 DOI: 10.1016/j.jneuroim.2019.577022] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Revised: 08/13/2019] [Accepted: 08/13/2019] [Indexed: 01/20/2023]
Abstract
An important extrahepatic consequence of Hepatitis C is its adverse impact on the central nervous system and cognitive performance. We aimed to determine whether there is a significant relationship between selected neurotransmitters and cytokines and cognitive performance in patients with Chronic Hepatitis C before and after achieving sustained virologic response (SVR). Pre-SVR, elevated kynurenine was associated with increased immediate and delayed visual memory, whereas post-SVR the positive associations are between kynurenine and immediate and delayed verbal memory. TGF-B was consistently negatively associated with both immediate and delayed visual memory pre- and post-SVR. These concomitant changes may have important clinical relevance.
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Affiliation(s)
- Ali A Weinstein
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, United States; Center for the Study of Chronic Illness and Disability, George Mason University, Fairfax, VA, United States
| | - J Michael Estep
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, United States
| | - Leyla de Avila
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, United States
| | - Michael Curry
- Beth Israel Deaconess Medical Center, Boston, MA, United States
| | - Pegah Golabi
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, United States
| | - Carey Escheik
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, United States
| | - Aybike Birerdinc
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, United States
| | - Maria Stepanova
- Center for Outcomes Research in Liver Diseases, Washington, DC, United States
| | - Jillian K Price
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, United States
| | - Lynn Gerber
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, United States; Center for the Study of Chronic Illness and Disability, George Mason University, Fairfax, VA, United States; Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, VA, United States
| | - Zobair M Younossi
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, United States; Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, VA, United States.
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Amirsardari Z, Rahmani F, Rezaei N. Cognitive impairments in HCV infection: From pathogenesis to neuroimaging. J Clin Exp Neuropsychol 2019; 41:987-1000. [PMID: 31405320 DOI: 10.1080/13803395.2019.1652728] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Extrahepatic manifestations of hepatitis C virus (HCV) infection, in particular cognitive impairments, can be present in the absence of clinical liver dysfunction. Executive memory, attention, and concentration are cognitive domains that are most frequently affected. Microstructural and functional changes in cortical gray matter and basal ganglia associate these neuropsychiatric changes in early HCV infection. No study has covered the relationship between imaging features of HCV-related cognitive impairment and HCV pathology. Herein we summarize evidence suggesting a direct pathology of HCV in microglia, astrocytes, and microvascular endothelial cells, and a neuroinflammatory response in HCV-related cognitive decline. Lipoproteins and their receptors mediate HCV infectivity in the central nervous system and confer susceptibility to HCV-related cognitive decline. Magnetic resonance spectroscopy has revealed changes compatible with reactive gliosis and microglial activation in basal ganglia, frontal and occipital white matter, in the absence of cirrhosis or hepatic encephalopathy. Similarly, diffusion imaging shows evidence of structural disintegrity in the axonal fibers of white matter tracts associated with temporal and frontal cortices. We also discuss the cognitive benefits and side-effects of the two most popular therapeutic protocols interferon-based therapy and interferon-free therapy using direct acting anti-virals. Evidences support a network-based pattern of disruption in functional connectivity in HCV patients and a common neuronal substrate for HCV-related and interferon-therapy-associated cognitive decline. These evidences might help identify patients who benefit from either interferon-based or interferon-free treatment regimen.
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Affiliation(s)
- Zahra Amirsardari
- Student's Scientific Research Center (SSRC), Tehran University of Medical Sciences , Tehran , Iran.,NeuroImaging Network (NIN), Universal Scientific Education and Research Network (USERN) , Tehran , Iran
| | - Farzaneh Rahmani
- Student's Scientific Research Center (SSRC), Tehran University of Medical Sciences , Tehran , Iran.,NeuroImaging Network (NIN), Universal Scientific Education and Research Network (USERN) , Tehran , Iran
| | - Nima Rezaei
- NeuroImaging Network (NIN), Universal Scientific Education and Research Network (USERN) , Tehran , Iran.,Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences , Tehran , Iran
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Fabbiani M, Ciccarelli N, Castelli V, Soria A, Borghetti A, Colella E, Moschese D, Valsecchi M, Emiliozzi A, Gori A, De Luca A, Bandera A, Di Giambenedetto S. Hepatitis C virus-related factors associated WITH cognitive performance in HIV-HCV-coinfected patients. J Neurovirol 2019; 25:866-873. [PMID: 31281946 DOI: 10.1007/s13365-019-00780-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Revised: 06/10/2019] [Accepted: 06/19/2019] [Indexed: 02/07/2023]
Abstract
The contribution of HCV-related variables to cognitive impairment in HIV-HCV-coinfected patients has been poorly investigated. We selected HIV-HCV-coinfected patients undergoing cognitive examination (exploring memory, language, speed of mental processing and fine motor function) at three clinical centres. Cognitive performance was evaluated using Z-transformed scores. Logistic regression analysis was used to investigate variables associated to cognitive impairment (defined as a composite Z-score ≤ - 1). Overall, 146 HIV-HCV-coinfected patients were enrolled. Median HCV-RNA was 6.2logU/mL. HCV genotype 1a/b was the most represented (53.4%). Liver fibrosis was mild (Fib4 ≤ 1.45) in the majority of patients (44.5%). Global cognitive impairment was diagnosed in 35 (24%) subjects. Exploring each domain, a higher proportion of impairment was observed for memory (37%) followed by speed of mental processing (32.2%), fine motor functioning (24%) and language (18.5%). Among HCV-related variables, the duration of HCV infection was independently associated with global cognitive impairment (aOR 1.13 per +1 year, p = 0.016) and abnormal speed of mental processing (aOR 1.16 per +1 year, p = 0.001), while higher HCV-RNA was independently associated to fine motor functioning impairment (aOR 1.98 per +1log, p = 0.037). HCV genotype, fibrosis stage, transaminases or bilirubin levels were not related to cognitive performance. Of note, integrase inhibitor (InSTI) use was independently associated to a pathological performance in fine motor functioning (aOR 3.34, p = 0.035) and memory (aOR 3.70, p = 0.014). In conclusion, the duration of HCV infection and HCV-RNA load showed an association with cognitive impairment, suggesting a role of hepatitis-related factors in the development of cognitive disorders in HIV-HCV-coinfected patients. The association between InSTI use and altered cognitive performance should prompt investigations about potential neurotoxicity of these drugs.
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Affiliation(s)
- Massimiliano Fabbiani
- Infectious Diseases Unit, Fondazione IRCCS Policlinico San Matteo, viale Golgi 19, 27100, Pavia, Italy.
| | - Nicoletta Ciccarelli
- Department of Psychology, Catholic University, Largo Gemelli 1, 20123, Milan, Italy
| | - Valeria Castelli
- Infectious Diseases Unit, S. Gerardo Hospital, via Pergolesi 33, 20900, Monza, Italy
| | - Alessandro Soria
- Infectious Diseases Unit, S. Gerardo Hospital, via Pergolesi 33, 20900, Monza, Italy
| | - Alberto Borghetti
- Institute of Clinical Infectious Diseases, Fondazione Gemelli, IRCCS, Catholic University, Largo Gemelli 8, 00168, Rome, Italy
| | - Elisa Colella
- Infectious Diseases Unit, S. Gerardo Hospital, via Pergolesi 33, 20900, Monza, Italy
| | - Davide Moschese
- Institute of Clinical Infectious Diseases, Fondazione Gemelli, IRCCS, Catholic University, Largo Gemelli 8, 00168, Rome, Italy
| | - Manuela Valsecchi
- Infectious Diseases Unit, S. Gerardo Hospital, via Pergolesi 33, 20900, Monza, Italy
| | - Arianna Emiliozzi
- Institute of Clinical Infectious Diseases, Fondazione Gemelli, IRCCS, Catholic University, Largo Gemelli 8, 00168, Rome, Italy
| | - Andrea Gori
- Infectious Diseases Unit, S. Gerardo Hospital, via Pergolesi 33, 20900, Monza, Italy
| | - Andrea De Luca
- Department of Medical Biotechnologies, University of Siena, viale Bracci 16, 53100, Siena, Italy
| | - Alessandra Bandera
- Infectious Diseases Unit, S. Gerardo Hospital, via Pergolesi 33, 20900, Monza, Italy
| | - Simona Di Giambenedetto
- Institute of Clinical Infectious Diseases, Fondazione Gemelli, IRCCS, Catholic University, Largo Gemelli 8, 00168, Rome, Italy
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Rei A, Rocha M, Pedroto I. Improving Health-Related Quality of Life Assessment in Chronic Hepatitis C. GE PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2019; 26:150-151. [PMID: 30976627 PMCID: PMC6454384 DOI: 10.1159/000488507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/27/2018] [Accepted: 03/09/2018] [Indexed: 06/09/2023]
Affiliation(s)
- Andreia Rei
- aInstituto de Ciências Biomédicas Abel Salazar (ICBAS), Medical College, University of Porto (UP), Porto, Portugal
| | - Marta Rocha
- bGastroenterology Department, Hospital de Santo António (HSA), Centro Hospitalar do Porto (CHP), Porto, Portugal
| | - Isabel Pedroto
- bGastroenterology Department, Hospital de Santo António (HSA), Centro Hospitalar do Porto (CHP), Porto, Portugal
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Brain metabolic and functional alterations in a liver-specific PTEN knockout mouse model. PLoS One 2018; 13:e0204043. [PMID: 30235271 PMCID: PMC6147462 DOI: 10.1371/journal.pone.0204043] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2018] [Accepted: 08/31/2018] [Indexed: 01/11/2023] Open
Abstract
Insulin resistance-as observed in aging, diabetes, obesity, and other pathophysiological situations, affects brain function, for insulin signaling is responsible for neuronal glucose transport and control of energy homeostasis and is involved in the regulation of neuronal growth and synaptic plasticity. This study investigates brain metabolism and function in a liver-specific Phosphatase and Tensin Homologue (Pten) knockout mouse model (Liver-PtenKO), a negative regulator of insulin signaling. The Liver-PtenKO mouse model showed an increased flux of glucose into the liver-thus resulting in an overall hypoglycemic and hypoinsulinemic state-and significantly lower hepatic production of the ketone body beta-hydroxybutyrate (as compared with age-matched control mice). The Liver-PtenKO mice exhibited increased brain glucose uptake, improved rate of glycolysis and flux of metabolites in the TCA cycle, and improved synaptic plasticity in the hippocampus. Brain slices from both control- and Liver-PtenKO mice responded to the addition of insulin (in terms of pAKT/AKT levels), thereby neglecting an insulin resistance scenario. This study underscores the significance of insulin signaling in brain bioenergetics and function and helps recognize deficits in diseases associated with insulin resistance.
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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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de Almeida SM, de Pereira AP, Pedroso MLA, Ribeiro CE, Rotta I, Tang B, Umlauf A, Franklin D, Saloner RG, Batista MGR, Letendre S, Heaton RK, Ellis RJ, Cherner M. Neurocognitive impairment with hepatitis C and HIV co-infection in Southern Brazil. J Neurovirol 2018. [PMID: 29516346 PMCID: PMC5993600 DOI: 10.1007/s13365-018-0617-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Although cognitive impairment has been well documented in human immunodeficiency virus (HIV) and hepatitis C virus (HCV) mono-infections, research on neurocognitive effects is limited in the context of HIV/HCV co-infection. The aims of this study were to explore the interplay between HIV and HCV infections in the expression of neurocognitive impairment (NCI), and to examine the differences in test performance between HIV/HCV co-infected and HIV or HCV mono-infected patients. A total of 128 participants from Southern Brazil underwent a comprehensive neuropsychological (NP) battery comprising 18 tests. Participants were grouped according to their serological status: HCV mono-infected (n = 20), HIV mono-infected (n = 48), HIV/HCV co-infected (n = 12), and HIV-/HCV-uninfected controls (n = 48). The frequencies of HIV subtypes B and C between the HIV mono-infected and HIV/HCV co-infected groups were comparable. There was greater prevalence of neuropsychological impairment among all three infection groups compared with the uninfected control group, but no statistically significant differences among mono- and co-infected groups were found. HCV infection was associated with cognitive deficits, independently of liver dysfunction. HCV infection did not show an additive effect on neurocognitive function among HIV+. NCI was independent of HCV RNA on peripheral blood, CSF, and hepatic injury. While we did not find additive global effect, in the present study, there was some evidence of additive HIV/HCV co-infection effects in speed of information processing, executive function, and verbal fluency domains when comparing the co-infected group with the other three groups. NP impairment was not dependent on HCV subtypes.
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Affiliation(s)
- Sérgio Monteiro de Almeida
- Hospital de Clínicas-UFPR, Universidade Federal do Paraná, Seção de Virologia, Setor Análises Clínicas, Rua Padre Camargo, 280, Curitiba, PR, 80060-240, Brazil.
- Faculdades Pequeno Príncipe, Curitiba, Paraná, Brazil.
- Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Paraná, Brazil.
| | - Ana Paula de Pereira
- Hospital de Clínicas-UFPR, Universidade Federal do Paraná, Seção de Virologia, Setor Análises Clínicas, Rua Padre Camargo, 280, Curitiba, PR, 80060-240, Brazil
| | - Maria Lucia Alves Pedroso
- Hospital de Clínicas-UFPR, Universidade Federal do Paraná, Seção de Virologia, Setor Análises Clínicas, Rua Padre Camargo, 280, Curitiba, PR, 80060-240, Brazil
| | - Clea E Ribeiro
- Hospital de Clínicas-UFPR, Universidade Federal do Paraná, Seção de Virologia, Setor Análises Clínicas, Rua Padre Camargo, 280, Curitiba, PR, 80060-240, Brazil
| | - Indianara Rotta
- Hospital de Clínicas-UFPR, Universidade Federal do Paraná, Seção de Virologia, Setor Análises Clínicas, Rua Padre Camargo, 280, Curitiba, PR, 80060-240, Brazil
- Faculdades Pequeno Príncipe, Curitiba, Paraná, Brazil
- Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Paraná, Brazil
| | - Bin Tang
- University of California San Diego, San Diego, CA, USA
| | - Anya Umlauf
- University of California San Diego, San Diego, CA, USA
| | | | | | - Maria Geny Ribas Batista
- Hospital de Clínicas-UFPR, Universidade Federal do Paraná, Seção de Virologia, Setor Análises Clínicas, Rua Padre Camargo, 280, Curitiba, PR, 80060-240, Brazil
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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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Barbosa MED, Zaninotto AL, de Campos Mazo DF, Pessoa MG, de Oliveira CPMS, Carrilho FJ, Farias AQ. Hepatitis C virus eradication improves immediate and delayed episodic memory in patients treated with interferon and ribavirin. BMC Gastroenterol 2017; 17:122. [PMID: 29178838 PMCID: PMC5702148 DOI: 10.1186/s12876-017-0679-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2017] [Accepted: 11/15/2017] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Chronic hepatitis C virus (HCV) infection is associated with impairment of cognitive function and mood disorders. Our aim was to evaluate the impact of sustained virological response (SVR) on cognitive function and mood disorders. METHOD A prospective exploratory one arm study was conducted. Adult clinically compensated HVC patients were consecutively recruited before treatment with interferon and ribavirin for 24 to 48 weeks, according to HCV genotype. Clinical, neurocognitive and mood assessments using the PRIME-MD and BDI instruments were performed at baseline, right after half of the expected treatment has been reached and 6 months after the end of antiviral treatment. Exclusion criteria were the use of illicit psychotropic substances, mental confusion, hepatic encephalopathy, hepatocellular carcinoma, severe anemia, untreated hypothyroidism, Addison syndrome and major depression before treatment. RESULTS Thirty six patients were enrolled and 21 completed HCV treatment (n = 16 with SVR and n = 5 without). Regardless of the viral clearance at the end of treatment, there was a significant improvement in the immediate verbal episodic memory (p = 0.010), delayed verbal episodic memory (p = 0.007), selective attention (p < 0.001) and phonemic fluency (p = 0.043). Patients with SVR displayed significant improvement in immediate (p = 0.045) and delayed verbal episodic memory (p = 0.040) compared to baseline. The baseline frequency of depression was 9.5%, which rose to 52.4% during treatment, and returned to 9.5% 6 months after the end of treatment, without significant difference between patients with and without SVR. Depressive symptoms were observed in 19.1% before treatment, 62% during (p = 0.016) and 28.6% 6 months after the end of treatment (p = 0.719). CONCLUSIONS Eradication of HCV infection improved cognitive performance but did not affect the frequency of depressive symptoms at least in the short range.
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Affiliation(s)
- Mary Ellen Dias Barbosa
- Division of Psychology, Clinics Hospital, University of Sao Paulo School of Medicine, Avenida Dr. Eneas Carvalho de Aguiar, 255, São Paulo, 05403-900 Brazil
- Division of Clinical Gastroenterology and Hepatology, Clinics Hospital, Department of Gastroenterology, University of São Paulo School of Medicine, Avenida Dr. Eneas Carvalho de Aguiar, 255, sala 9159, São Paulo, 05403-900 Brazil
- Department of Gastroenterology, University of Sao Paulo School of Medicine, Av. Dr. Enéas de Carvalho Aguiar n° 255, São Paulo, 05403-000 Brazil
| | - Ana Luiza Zaninotto
- Division of Psychology, Clinics Hospital, University of Sao Paulo School of Medicine, Avenida Dr. Eneas Carvalho de Aguiar, 255, São Paulo, 05403-900 Brazil
| | - Daniel Ferraz de Campos Mazo
- Division of Clinical Gastroenterology and Hepatology, Clinics Hospital, Department of Gastroenterology, University of São Paulo School of Medicine, Avenida Dr. Eneas Carvalho de Aguiar, 255, sala 9159, São Paulo, 05403-900 Brazil
- Division of Gastroenterology, School of Medical Sciences, University of Campinas, Rua Carlos Chagas, 420, Campinas, 13083-878 Brazil
| | - Mario Guimarães Pessoa
- Division of Clinical Gastroenterology and Hepatology, Clinics Hospital, Department of Gastroenterology, University of São Paulo School of Medicine, Avenida Dr. Eneas Carvalho de Aguiar, 255, sala 9159, São Paulo, 05403-900 Brazil
| | - Cláudia Pinto Marques Souza de Oliveira
- Division of Clinical Gastroenterology and Hepatology, Clinics Hospital, Department of Gastroenterology, University of São Paulo School of Medicine, Avenida Dr. Eneas Carvalho de Aguiar, 255, sala 9159, São Paulo, 05403-900 Brazil
| | - Flair José Carrilho
- Division of Clinical Gastroenterology and Hepatology, Clinics Hospital, Department of Gastroenterology, University of São Paulo School of Medicine, Avenida Dr. Eneas Carvalho de Aguiar, 255, sala 9159, São Paulo, 05403-900 Brazil
| | - Alberto Queiroz Farias
- Division of Clinical Gastroenterology and Hepatology, Clinics Hospital, Department of Gastroenterology, University of São Paulo School of Medicine, Avenida Dr. Eneas Carvalho de Aguiar, 255, sala 9159, São Paulo, 05403-900 Brazil
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Shirazi TN, Summers AC, Smith BR, Steinbach SR, Kapetanovic S, Nath A, Snow J. Concordance Between Self-Report and Performance-Based Measures of Everyday Functioning in HIV-Associated Neurocognitive Disorders. AIDS Behav 2017; 21:2124-2134. [PMID: 28108876 PMCID: PMC11371461 DOI: 10.1007/s10461-017-1689-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Self-report is typically used to differentiate between asymptomatic neurocognitive impairment (ANI) and mild neurocognitive disorder (MND) in the assessment of HIV-associated neurocognitive disorders (HAND). Yet, it is unclear whether the lack of self-reported functional impairments in individuals with ANI is indicative of a genuine absence of functional impairment, or of inaccurate self-reports. In the present study, we examined the relationship between previously validated self-report (patient's assessment of own functioning inventory; instrumental activities of daily living inventory) and performance-based (the Texas Functional Living Scale) measures of functional abilities in 112 virologically-controlled HIV-infected, and 40 well-matched, HIV-uninfected participants. Participants with symptomatic cognitive impairment (CI) had significantly lower overall scores and higher rates of impairment on a performance-based measure of everyday functioning as compared to participants with either asymptomatic CI or normal cognitive performance (WNL [within normal limits]; all p < 0.05), while asymptomatic CI and WNL participants had comparable rates of impairment and performance within the average range on the performance-based measure. The concordance between self-report and performance-based measures of everyday functioning in asymptomatic and symptomatic CI provide support for ANI and MND as clinically distinct diagnostic entities, and support the use of self-reports as appropriate measures of everyday functioning in the diagnosis of HAND.
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Affiliation(s)
- Talia N Shirazi
- Office of the Clinical Director, National Institute of Mental Health, National Institutes of Health, 10 Center Drive room 3n218, Bethesda, MD, 20814, USA.
| | - Angela C Summers
- Office of the Clinical Director, National Institute of Mental Health, National Institutes of Health, 10 Center Drive room 3n218, Bethesda, MD, 20814, USA
| | - Bryan R Smith
- Section of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
| | - Sally R Steinbach
- Section of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
- Clinical Research Directorate/Clinical Monitoring Research Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, MD, 21702, USA
| | - Suad Kapetanovic
- Office of the Clinical Director, National Institute of Mental Health, National Institutes of Health, 10 Center Drive room 3n218, Bethesda, MD, 20814, USA
- Department of Psychiatry and the Behavioral Sciences, University of Southern California Keck School of Medicine, Los Angeles, CA, USA
| | - Avindra Nath
- Section of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
| | - Joseph Snow
- Office of the Clinical Director, National Institute of Mental Health, National Institutes of Health, 10 Center Drive room 3n218, Bethesda, MD, 20814, USA
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Lin HC, Xirasagar S, Lee HC, Huang CC, Chen CH. Association of Alzhemier's disease with hepatitis C among patients with bipolar disorder. PLoS One 2017. [PMID: 28622343 PMCID: PMC5473552 DOI: 10.1371/journal.pone.0179312] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Associations of hepatitis C virus infection with Alzheimer’s disease have not been studied among higher risk, bipolar disorder patients. This population-based case-control study investigated the risks of hepatitis C virus infection among Alzheimer’s disease patients with bipolar disorder in the years preceding their Alzheimer’s disease diagnosis. We used 2000–2013 data from the Longitudinal Health Insurance Database in Taiwan. Among patients with bipolar disorder, 73 were diagnosed with Alzheimer’s disease (cases), who were compared with 365 individuals with bipolar disorder but without Alzheimer’s disease (randomly selected controls matched on sex, age, and index year with cases). Prior claims (before the diagnosis year/index year for controls) were screened for a diagnosis of hepatitis C virus infection. Conditional logistic regression models were used for analysis. We found that 23 (31.51%) and 60 (16.44%) patients with bipolar disease were identified with a hepatitis C diagnosis among those with and without Alzheimer’s disease, respectively. Compared to controls, patients with Alzheimer’s disease showed 2.31-fold (95% confidence interval = 1.28–4.16) increased risk of hepatitis C infections adjusted for demographics and socio-economic status. Findings suggest an association of Alzheimer’s disease with a preceding diagnosis of hepatitis C infection among patients with bipolar disorder. Findings may suggest a need for increased awareness of and appropriate surveillance for Alzheimer’s disease in patients with bipolar disorder diagnosed with hepatitis C infection.
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Affiliation(s)
- Herng-Ching Lin
- School of Health Care Administration, Taipei Medical University, Taipei, Taiwan
- Sleep Research Center, Taipei Medical University Hospital, Taipei, Taiwan
| | - Sudha Xirasagar
- Department of Health Services Policy and Management, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina, United States of America
| | - Hsin-Chien Lee
- Department of Psychiatry, Taipei Medical University-Shuang-Ho Hospital, Taipei, Taiwan
- Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Chung-Chien Huang
- School of Health Care Administration, Taipei Medical University, Taipei, Taiwan
| | - Chao-Hung Chen
- Department & Institute of Physiology, National Yang-Ming University, Taipei, Taiwan
- Department of Cosmetic Applications and Management, Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan
- Department of Thoracic Surgery, MacKay Memorial Hospital, Taipei, Taiwan
- Research Center of Sleep Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- * E-mail:
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39
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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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40
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Mendis SB, Lukats V. Diagnostic conundrum: lessons from the man who accidently set fire to his home. BMJ Case Rep 2016; 2016:bcr-2016-215642. [PMID: 27856530 DOI: 10.1136/bcr-2016-215642] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
A 62-year-old man presented to psychiatric services with a 3-month history of a range of symptoms which included obsessional thoughts, self-neglect, lack of mental flexibility, reduced ability to plan, organise and follow instructions, reduced capacity to empathise and disinhibition. He also accidently set fire to his house. Overall these findings are compatible with a dysexecutive syndrome. This man has a significant history of polysubstance misuse and chronic hepatitis C infection. Neuroimaging revealed an acquired traumatic brain injury which could account for his dysexecutive syndrome. The patient was managed in a holistic manner. A community psychiatric nurse was allocated, he had social services input and he was started on trazodone. He is currently housed in short-term housing and is awaiting a long-term residential placement.
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Affiliation(s)
- Sahan Benedict Mendis
- Department of Brunswick Ward, Sussex Partnership NHS Foundation Trust, Hove, UK.,Brighton and Sussex Medical School, Trafford Centre, Brighton, UK
| | - Victoria Lukats
- Department of Brunswick Ward, Sussex Partnership NHS Foundation Trust, Hove, UK
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41
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Dantas-Duarte A, Morais-de-Jesus M, Nunes AP, Miranda-Pettersen K, Araújo-de-Freitas L, Netto LR, Santos CT, Codes L, Quarantini LC. Risk-taking behavior and impulsivity among HCV-infected patients. Psychiatry Res 2016; 243:75-80. [PMID: 27371803 DOI: 10.1016/j.psychres.2016.04.114] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2015] [Revised: 03/02/2016] [Accepted: 04/29/2016] [Indexed: 12/22/2022]
Abstract
The association between risk behaviors and hepatitis C virus (HCV) has been extensively studied. It is also proved that impulsivity is associated with risk behaviors. However, there is a lack of studies investigating the association between HCV and impulsivity, a characteristic that can contribute directly to these risk behaviors. This study aimed to investigate HCV-infected individuals' impulsivity and whether this feature mediates risk behavior. Adult patients with liver diseases (n=269) were divided into two groups: viral group (n=157) - patients with HCV and nonviral group (n=112). Risk behaviors were evaluated by a sociodemographic questionnaire. Impulsivity was assessed through Barratt Impulsiveness Scale - BIS-11. Psychiatric comorbidities were investigated by the Mini International Neuropsychiatric Interview 5.0.0. The viral group patients had higher impulsivity than the nonviral group in all domains: attentional impulsivity, motor impulsivity, and nonplanning. Risk behaviors were also shown to be associated with impulsivity levels. Our results suggest that HCV-infected patients are more impulsive than individuals with other liver diseases, even when analyses are controlled for the presence of comorbid mental disorders. In addition, at-risk behavior was significantly mediated by impulsivity.
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Affiliation(s)
- Adriana Dantas-Duarte
- Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Universidade Federal da Bahia, Salvador, Bahia, Brazil
| | - Mychelle Morais-de-Jesus
- Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Universidade Federal da Bahia, Salvador, Bahia, Brazil
| | - Ana Paula Nunes
- Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Universidade Federal da Bahia, Salvador, Bahia, Brazil
| | - Karine Miranda-Pettersen
- Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Universidade Federal da Bahia, Salvador, Bahia, Brazil
| | - Lucas Araújo-de-Freitas
- Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Universidade Federal da Bahia, Salvador, Bahia, Brazil
| | - Liana R Netto
- Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Universidade Federal da Bahia, Salvador, Bahia, Brazil
| | - Carlos Teles Santos
- Departamento de Ciências Exatas, Universidade Estadual de Feira de Santana, Feira de Santana, Bahia, Brazil; Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador, Bahia, Brazil
| | - Liana Codes
- Hospital Universitário da Universidade Federal da Bahia, Salvador, Bahia, Brazil
| | - Lucas C Quarantini
- Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Universidade Federal da Bahia, Salvador, Bahia, Brazil; Hospital Universitário da Universidade Federal da Bahia, Salvador, Bahia, Brazil.
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42
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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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43
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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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44
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Hjerrild S, Renvillard SG, Leutscher P, Sørensen LH, Østergaard L, Eskildsen SF, Videbech P. Reduced cerebral cortical thickness in Non-cirrhotic patients with hepatitis C. Metab Brain Dis 2016; 31:311-9. [PMID: 26530221 DOI: 10.1007/s11011-015-9752-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2015] [Accepted: 10/21/2015] [Indexed: 02/06/2023]
Abstract
Hepatitis C virus (HCV) infection is associated with fatigue, depression, and cognitive impairment even in the absence of severe liver fibrosis or cirrhosis. HCV has been hypothesised to cause neurodegenerative changes through low-grade neuroinflammation. Our aim was to examine whether cortical thickness (CTh) differs between chronic HCV patients and healthy controls, suggestive of cortical atrophy. In this case-control study 43 HCV patients without severe liver fibrosis, substance abuse, or comorbid HIV or hepatitis B virus infection, and 43 age and sex matched controls underwent MRI. Cortical thickness was measured using a surface based approach. Participants underwent semi-structured psychiatric interview and fatigue was assessed using the fatigue severity scale. HCV was associated with higher fatigue scores, and 58 % of HCV patients suffered from significant fatigue (p < 0.0001). Depression was observed in 16 % of patients. Areas of significantly reduced CTh were found in both left and right occipital cortex and in the left frontal lobe after correction for multiple comparisons (p < 0.05). No association between fatigue, former substance abuse, or psychotropic medication and CTh was found. No overall difference in cerebral white and grey matter volume was found. The findings support the hypothesis that HCV is associated with neurodegenerative changes.
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Affiliation(s)
- Simon Hjerrild
- Department for Affective Disorders, Aarhus University Hospital, Skovagervej 2, 8240, Risskov, Denmark.
- Center of Functionally Integrative Neuroscience (CFIN), Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
| | - Signe Groth Renvillard
- Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark
- Department for Affective Disorders, Aarhus University Hospital, Skovagervej 2, 8240, Risskov, Denmark
| | - Peter Leutscher
- Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark
| | | | - Leif Østergaard
- Center of Functionally Integrative Neuroscience (CFIN), Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Simon Fristed Eskildsen
- Center of Functionally Integrative Neuroscience (CFIN), Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Poul Videbech
- Department for Affective Disorders, Aarhus University Hospital, Skovagervej 2, 8240, Risskov, Denmark
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45
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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: 120] [Impact Index Per Article: 13.3] [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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46
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Infectious disease burden and cognitive function in young to middle-aged adults. Brain Behav Immun 2016; 52:161-168. [PMID: 26598104 DOI: 10.1016/j.bbi.2015.10.014] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2015] [Revised: 10/23/2015] [Accepted: 10/23/2015] [Indexed: 11/20/2022] Open
Abstract
Prior research has suggested an association between exposure to infectious disease and neurocognitive function in humans. While most of these studies have explored individual viral, bacterial, and even parasitic sources of infection, few have considered the potential neurocognitive burden associated with multiple infections. In this study, we utilized publically available data from a large dataset produced by the Centers for Disease Control and Prevention that included measures of neurocognitive function, sociodemographic variables, and serum antibody data for several infectious diseases. Specifically, immunoglobulin G antibodies for toxocariasis, toxoplasmosis, hepatitis A, hepatitis B, and hepatitis C, cytomegalovirus, and herpes 1 and 2 were available in 5662 subjects. We calculated an overall index of infectious-disease burden to determine if an aggregate measure of exposure to infectious disease would be associated with neurocognitive function in adults aged 20-59 years. The index predicted processing speed and learning and memory but not reaction time after controlling for age, sex, race-ethnicity, immigration status, education, and the poverty-to-income ratio. Interactions between the infectious-disease index and some sociodemographic variables were also associated with neurocognitive function. In summary, an index aggregating exposure to several infectious diseases was associated with neurocognitive function in young- to middle-aged adults.
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47
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Gerber L, Estep M, Stepanova M, Escheik C, Weinstein A, Younossi ZM. Effects of Viral Eradication With Ledipasvir and Sofosbuvir, With or Without Ribavirin, on Measures of Fatigue in Patients With Chronic Hepatitis C Virus Infection. Clin Gastroenterol Hepatol 2016; 14:156-64.e3. [PMID: 26241510 DOI: 10.1016/j.cgh.2015.07.035] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2015] [Accepted: 07/22/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Fatigue is a disturbing symptom of chronic hepatitis C virus (HCV) infection. We assessed the effects of sustained virologic response 12 weeks after the end of therapy (SVR12) on fatigue. METHODS We performed a retrospective analysis of 100 patients with chronic HCV infection who achieved an SVR12 after treatment with ledipasvir and sofosbuvir, with or without ribavirin. Data were collected on fatigue-related patient-reported outcomes (PROs) and assessed by using the Functional Assessment of Cancer Therapy-Fatigue scoring system and the Vitality subscale of Short Form 36. We measured levels of cytokines and growth factors in frozen serum samples collected at baseline, week 12 of treatment, and 4 weeks after treatment. Central fatigue and peripheral or muscle fatigue (PF) were determined by using items from PROs. Serum levels of cytokines, growth factors, serotonin, alanine aminotransferase, and aspartate aminotransferase were measured by using the Bio-Plex, enzyme-linked immunosorbent, and enzymatic assays. RESULTS Compared with baseline, 4 weeks after the end of treatment, all fatigue-associated PROs improved significantly. Baseline PROs correlated inversely with serum level of interferon-γ; level of platelet-derived growth factor correlated with PF, central fatigue, and total fatigue score. Only PF correlated with serum level of serotonin. At baseline, high PF scores correlated with high serum levels of serotonin and low levels of interleukin-10 and tumor necrosis factor-α. In multivariate analysis, serum level of interleukin-8 was associated with greater fatigue (P < .02). Reductions in levels of chemokine (C-C motif) ligand 2 (also called monocyte chemotactic protein 1) were associated with fatigue after treatment (P = .0165). CONCLUSIONS In an analysis of data from patients with chronic HCV infection participating in a clinical trial of ledipasvir and sofosbuvir, SVR12 was associated with reduced fatigue, compared with baseline. High baseline serum levels of interferon-γ were associated with fatigue. Reductions in levels of chemokine (C-C motif) ligand 2 were associated with persistent fatigue after SVR12. Central and peripheral fatigue each associated with different biomarkers, suggesting different pathogenic pathways.
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Affiliation(s)
- Lynn Gerber
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia
| | - Michael Estep
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia; Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia
| | - Maria Stepanova
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia
| | - Carey Escheik
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia
| | - Ali Weinstein
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia
| | - Zobair M Younossi
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia; Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia.
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48
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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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49
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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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