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Pawłowski T, Radkowski M, Perlejewski K, Szymańska B, Berak H, Horban A, Laskus T. Direct-acting antivirals (DAA) positively affect depression and cognitive function in patients with chronic hepatitis C. PLoS One 2025; 20:e0320221. [PMID: 40184345 PMCID: PMC11970650 DOI: 10.1371/journal.pone.0320221] [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] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Accepted: 02/16/2025] [Indexed: 04/06/2025] Open
Abstract
The aim of the study was to determine how depression and cognitive dysfunction in patients with chronic hepatitis C virus (HCV) infection are affected by treatment with direct-acting antivirals (DAA). Fifty-two chronic hepatitis C patients underwent neurocognitive and psychological evaluation before therapy and 5-6 months later. Depression was measured by Beck Depression Inventory (BDI), anxiety by State-Trait Anxiety inventory (STAI), neuroticism by Eysenck Personality Inventory (N/EPO-R), while Ruff Figural Fluency Test (RFFT), Wisconsin Card Sorting Test (WCST), The Grooved Pegboard Test (GPT), and California Verbal Learning Test (CVLT) were used to assess neurocognitive function. There was significant positive change in BDI scores (8.8 ± 6.6 vs 6.1 ± 6.1; p < 0.0001) while the most striking improvement in cognitive tests was observed for CVLT sum of immediate recall from Trial-1 to Trial-5 (50.9 ± 10.0 to 54.1 ± 10.0; p = 0.0005) and RFFT, where the number of unique designs increased from 77.2 ± 21.0 to 86.1 ± 28.3 (p < 0.0001). These differences remained significant when patients with advanced (METAVIR grade F3/F4) and those with mild (grade F0/F1/F2) liver disease were analyzed separately, although in general the improvements were more pronounced in the former group. In conclusion, in chronic HCV infection the brain function is markedly improved by DAA treatment.
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Affiliation(s)
- Tomasz Pawłowski
- Department of Psychiatry, Wrocław Medical University, Wrocław, Poland
| | - Marek Radkowski
- Department of Immunopathology of Infectious and Parasitic Diseases, Medical University of Warsaw, Warsaw, Poland
| | - Karol Perlejewski
- Department of Immunopathology of Infectious and Parasitic Diseases, Medical University of Warsaw, Warsaw, Poland
| | - Bogna Szymańska
- Outpatient Clinic, Warsaw Hospital for Infectious Diseases, Warsaw, Poland
| | - Hanna Berak
- Outpatient Clinic, Warsaw Hospital for Infectious Diseases, Warsaw, Poland
| | - Andrzej Horban
- Department of Adult Infectious Diseases, Medical University of Warsaw, Warsaw, Poland
| | - Tomasz Laskus
- Department of Adult Infectious Diseases, Medical University of Warsaw, Warsaw, Poland
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Ocampo F, Sacdalan C, Pinyakorn S, Paudel M, Wansom T, Poltubtim N, Sriplienchan S, Phanuphak N, Paul R, Hsu D, Colby D, Trautmann L, Spudich S, Chan P. Neuropsychiatric and laboratory outcomes of hepatitis C treatment in an early-treated HIV cohort in Thailand. AIDS Res Ther 2025; 22:20. [PMID: 39972347 PMCID: PMC11841302 DOI: 10.1186/s12981-025-00707-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Accepted: 01/17/2025] [Indexed: 02/21/2025] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) coinfection may further compromise immunological and cognitive function in people with HIV (PWH). This study compared laboratory and neuropsychiatric measures across the periods of HCV seroconversion and direct-acting antiviral (DAA) therapy with sustained virologic response (SVR) among PWH who initiated antiretroviral therapy (ART) during acute HIV infection (AHI) and acquired HCV after 24 weeks of ART. METHODS Participants from the RV254 AHI cohort underwent paired laboratory and neuropsychiatric assessments during follow-up visits. The former included measurements of CD4 + and CD8 + T-cell counts, HIV RNA, liver enzymes, and lipid profiles. The latter included the Patient Health Questionnaire-9 (PHQ-9), Distress Thermometer (DT), and a 4-test cognitive battery that evaluated psychomotor speed, executive function, fine motor speed, and dexterity. The raw scores in the battery were standardized and averaged to create an aggregate performance (NPZ-4) score. Parameters of HCV-coinfected participants were compared across the periods of HCV seroconversion and DAA treatment. RESULTS Between 2009 and 2022, 79 of 703 RV254 participants acquired HCV after ≥ 24 weeks of ART; 53 received DAA, and 50 (94%) achieved SVR. All participants were Thai males (median age: 30 years); 34 (68%) denied past intravenous drug use, and 41 (82%) had a history of other sexually transmitted infections during follow-up. Following SVR, aspartate transferase (AST) and alanine transaminase (ALT) decreased (p < 0.001), while total cholesterol, low-density lipoprotein, and triglycerides increased (p < 0.01). The median CD4 + /CD8 + ratio increased from 0.91 to 0.97 (p = 0.012). NPZ-4 improved from 0.75 to 0.91 (p = 0.004). The median DT score increased from 1.7 to 2.7 (p = 0.045), but the PHQ-9 score remained unchanged. CONCLUSION HCV coinfection is common in this group of high-risk PWH, highlighting the need for regular screening, early diagnosis, and treatment. The study participants exhibited a modest improvement in the CD4 + /CD8 + T-cell ratio and cognitive performance following DAA therapy and SVR. Future studies should examine potential neuropsychiatric impacts during early HCV infection as well as the longer-term neuropsychiatric outcomes after DAA treatment with SVR.
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Affiliation(s)
- Ferron Ocampo
- SEARCH Research Foundation, Block 28, 926 Tower C Room C114-C115 Soi Chula 7, Wang Mai, Pathum Wan, Bangkok, 10330, Thailand.
| | - Carlo Sacdalan
- SEARCH Research Foundation, Block 28, 926 Tower C Room C114-C115 Soi Chula 7, Wang Mai, Pathum Wan, Bangkok, 10330, Thailand
- Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Suteeraporn Pinyakorn
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA
| | - Misti Paudel
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA
| | | | - Nathornsorn Poltubtim
- SEARCH Research Foundation, Block 28, 926 Tower C Room C114-C115 Soi Chula 7, Wang Mai, Pathum Wan, Bangkok, 10330, Thailand
| | - Somchai Sriplienchan
- SEARCH Research Foundation, Block 28, 926 Tower C Room C114-C115 Soi Chula 7, Wang Mai, Pathum Wan, Bangkok, 10330, Thailand
| | | | | | - Denise Hsu
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA
| | - Donn Colby
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA
| | - Lydie Trautmann
- U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA
| | - Serena Spudich
- Department of Neurology, Yale University, New Haven, CT, USA
- Yale Center for Brain and Mind Health, Yale University, New Haven, CT, USA
| | - Phillip Chan
- Department of Neurology, Yale University, New Haven, CT, USA
- Yale Center for Brain and Mind Health, Yale University, New Haven, CT, USA
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Ocampo FF, Sacdalan C, Pinyakorn S, Paudel M, Wansom T, Poltubtim N, Sriplienchan S, Phanuphak N, Paul R, Hsu D, Colby D, Trautmann L, Spudich S, Chan P. Neuropsychiatric and Laboratory Outcomes of Hepatitis C Treatment in an Early-Treated HIV Cohort in Thailand. RESEARCH SQUARE 2024:rs.3.rs-4186965. [PMID: 38645141 PMCID: PMC11030515 DOI: 10.21203/rs.3.rs-4186965/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/23/2024]
Abstract
Background Hepatitis C virus (HCV) coinfection may further compromise immunological and cognitive function in people with HIV (PWH). This study compared laboratory and neuropsychiatric measures across the periods of HCV seroconversion and direct-acting antiviral (DAA) therapy with sustained virologic response (SVR) among PWH who initiated antiretroviral therapy (ART) during acute HIV infection (AHI) and acquired HCV after 24 weeks of ART. Methods Participants from the RV254 AHI cohort underwent paired laboratory and neuropsychiatric assessments during regular follow-up. The former included measurements of CD4 + and CD8 + T-cell counts, HIV RNA, liver enzymes, and lipid profiles. The latter included the Patient Health Questionnaire-9 (PHQ-9), Distress Thermometer (DT), and a 4-test cognitive battery that evaluated psychomotor speed, executive function, fine motor speed and dexterity. The raw scores in the battery were standardized and averaged to create an overall performance (NPZ-4) score. Parameters of HCV-coinfected participants were compared across HCV seroconversion and DAA treatment groups. Results Between 2009 and 2022, 79 of 703 RV254 participants acquired HCV after ≥ 24 weeks of ART; 53 received DAA, and 50 (94%) achieved SVR. All participants were Thai males (median age: 30 years); 34 (68%) denied past intravenous drug use, and 41 (82%) had a history of other sexually transmitted infections during follow-up. Following SVR, aspartate transferase (AST) and alanine transaminase (ALT) decreased (p < 0.001), while total cholesterol, low-density lipoprotein, and triglycerides increased (p < 0.01). The median CD4+/CD8 + ratio increased from 0.91 to 0.97 (p = 0.012). NPZ-4 improved from 0.75 to 0.91 (p = 0.004). The median DT score increased from 1.7 to 2.7 (p = 0.045), but the PHQ-9 score remained unchanged. Conclusion HCV coinfection is common in this group of high-risk PWH, highlighting the need for regular screening, early diagnosis, and treatment. There was a modest improvement in the CD4+/CD8 + T-cell ratio and cognitive performance after DAA therapy in patients who achieved SVR. Future studies should examine potential neuropsychiatric impacts during early HCV infection as well as the longer-term neuropsychiatric outcomes after DAA treatment with SVR.
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Brunner N, Grischott T, Bruggmann P. Late presentation for hepatitis C treatment: prevalence and risk factors in the Swiss Hepatitis C Cohort. Eur J Gastroenterol Hepatol 2024; 36:326-331. [PMID: 38251444 DOI: 10.1097/meg.0000000000002705] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/23/2024]
Abstract
OBJECTIVE Patients with 'late presentation' (LP) of chronic hepatitis C infection (HCV) have already developed advanced liver disease before receiving direct-acting antiviral (DAA) treatment. Even after successful treatment, the risk of morbidity and premature death remains elevated, leading to an unnecessary disease burden. This study aimed to assess the prevalence of LP within the prospective observational Swiss Hepatitis C Cohort (SCCS) and evaluate risk factors as determinants of LP. METHODS Treatment-naïve participants of SCCS who received DAA treatment between 2014 and 2019 were included. Demographic, clinical and behavioural data were compared between the LP and non-LP strata. LP prevalence was calculated over time and by year. LASSO regression was used to identify potential risk factors for LP, and odds ratios were calculated by refitting logistic regression models. RESULTS In this explorative, retrospective case-control study using data of n = 5829 SCCS members, a total of 21.3% received their first HCV treatment. The cumulative LP prevalence decreased from mid-2015 and stabilised at 46.5% ( n = 579) by the end of 2019. Male gender, higher age and a history of alcohol overuse were associated with a higher risk of LP. CONCLUSION Despite the study's limitations, LP prevalence was higher than anticipated, considering Switzerland's availability period and universal access to DAAs. Therefore, any HCV LP should be viewed as a healthcare system failure, primarily in high-income economies. As LP is directly linked to the disease burden, it must be included as a mandatory parameter in surveillance response systems of HCV elimination programs.
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Affiliation(s)
| | - Thomas Grischott
- bInstitute of Primary Care, University Hospital Zurich, University of Zurich, Zurich, SwitzerlandGenevaBaselBerneLausanneLa Chaux-de-FondsLuganoNeuchâtelSt. GallenZurichBasel Clinical Trial Unit
| | - Philip Bruggmann
- Arud Centre for Addiction Medicine
- bInstitute of Primary Care, University Hospital Zurich, University of Zurich, Zurich, SwitzerlandGenevaBaselBerneLausanneLa Chaux-de-FondsLuganoNeuchâtelSt. GallenZurichBasel Clinical Trial Unit
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Radkowski M, Kryczka T, Szymańska-Kotwica B, Berak H, Horban A, Pawłowski T, Perlejewski K, Laskus T. Depression and Cognitive Dysfunction in Patients with Chronic Hepatitis C: Correlation with Viral Replication in the Peripheral Blood Mononuclear Cells and Cytokines in Serum. Int J Mol Sci 2023; 24:15351. [PMID: 37895030 PMCID: PMC10607636 DOI: 10.3390/ijms242015351] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Revised: 10/13/2023] [Accepted: 10/16/2023] [Indexed: 10/29/2023] Open
Abstract
Chronic hepatitis C virus (HCV) infection is commonly associated with depression and cognitive dysfunction, the cause of which could be related to the HCV neuroinvasion and/or state of chronic inflammation. Viral sequences and proteins were previously detected in the brain and since blood leukocytes can cross the blood-brain barrier, they could provide viral access to the CNS. Eighty chronic hepatitis C patients were tested for viral replication in PBMCs (detection of the HCV RNA-negative strand) and serum cytokines. Depression was assessed by the Beck Depression Inventory (BDI), neuroticism by the Eysenck Personality Inventory (N/EPO-R), and anxiety by the State-Trait Anxiety Inventory (STAI) while neurocognitive testing included the Wisconsin Card Sorting Test (WCST), Ruff Figural Fluency Test (RFFT), California Verbal Learning Test (CVLT), and Grooved Pegboard Test (GPT). The HCV RNA-negative strand was detected in PBMCs from 24 (30%) patients and these patients had significantly higher BDI scores (median 12.5 [IQR] 6.3-20.5 vs. median 8.00 [IQR] 3-12; p = 0.013). Both depression and anxiety correlated positively with IL-8 while cognitive flexibility, executive function, problem-solving skills, memory, and motor functioning correlated negatively with some proinflammatory cytokines. Our findings suggest that due to chronic HCV infection, the brain function is negatively affected by both viral replication in PBMCs and by the immune activation state.
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Affiliation(s)
- Marek Radkowski
- Department of Immunopathology of Infectious and Parasitic Diseases, Medical University of Warsaw, 02-106 Warsaw, Poland; (M.R.); (K.P.)
| | - Tomasz Kryczka
- Department of Development of Nursing and Social and Medical Sciences, Medical University of Warsaw, 01-445 Warsaw, Poland;
| | - Bogna Szymańska-Kotwica
- Outpatient Clinic, Warsaw Hospital for Infectious Diseases, 01-201 Warsaw, Poland; (B.S.-K.); (H.B.)
| | - Hanna Berak
- Outpatient Clinic, Warsaw Hospital for Infectious Diseases, 01-201 Warsaw, Poland; (B.S.-K.); (H.B.)
| | - Andrzej Horban
- Department of Adult Infectious Diseases, Medical University of Warsaw, 01-201 Warsaw, Poland
| | - Tomasz Pawłowski
- Department of Psychiatry, Wroclaw Medical University, 50-367 Wroclaw, Poland;
| | - Karol Perlejewski
- Department of Immunopathology of Infectious and Parasitic Diseases, Medical University of Warsaw, 02-106 Warsaw, Poland; (M.R.); (K.P.)
| | - Tomasz Laskus
- Department of Adult Infectious Diseases, Medical University of Warsaw, 01-201 Warsaw, Poland
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Amendola-Pires MM, Fakoury MK, Salazar H, De Oliveira SB, Brandão-Mello CE, Schmidt SL. Hepatitis C Virus (HCV) Infection and Neurocognitive Impairment in Subjects with Mild Liver Disease. J Clin Med 2023; 12:3910. [PMID: 37373605 DOI: 10.3390/jcm12123910] [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: 04/09/2023] [Revised: 05/12/2023] [Accepted: 05/25/2023] [Indexed: 06/29/2023] Open
Abstract
Hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis, hepatocellular carcinoma, and liver-related deaths. It is estimated that 40-74% of patients with hepatitis C will experience at least one extrahepatic manifestation within their lifetime. The finding of HCV-RNA sequences in post-mortem brain tissue raises the possibility that HCV infection may affect the central nervous system and be the source of subtle neuropsychological symptoms, even in non-cirrhotic. Our investigation aimed to evaluate whether asymptomatic, HCV-infected subjects showed cognitive dysfunctions. Twenty-eight untreated asymptomatic HCV subjects and 18 healthy controls were tested using three neuropsychological instruments in a random sequence: Symbol Digit Modalities Test (SDMT), Controlled Oral Word Association Test (COWAT), and Continuous Visual Attention Test (CVAT). We performed depression screening, liver fibrosis assessment, blood tests, genotyping, and HCV-RNA viral load. A MANCOVA and univariate ANCOVAS were performed to examine group differences (HCV vs. healthy controls) in four scores of the CVAT (omission errors, commission errors, reaction time-RT, and variability of RT-VRT), and the scores derived from the SDMT, and the COWAT. A discriminant analysis was performed to identify which test variables effectively discriminate HCV-infected subjects from healthy controls. There were no group differences in the scores of the COWAT, SDMT, and in two variables of the CVAT (omission and commission errors). In contrast, the performance of the HCV group was poorer than the controls in RT (p = 0.047) and VRT (p = 0.046). The discriminant analysis further indicated that the RT was the most reliable variable to discriminate the two groups with an accuracy of 71.7%. The higher RT exhibited by the HCV group may reflect deficits in the intrinsic-alertness attention subdomain. As the RT variable was found to be the best discriminator between HCV patients and controls, we suggest that intrinsic-alertness deficits in HCV patients may affect the stability of response times increasing VRT and leading to significant lapses in attention. In conclusion, HCV subjects with mild disease showed deficits in RT and intraindividual VRT as compared to healthy controls.
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Affiliation(s)
- Marcia Maria Amendola-Pires
- Postgraduate Program in Neurology, Neurobehavioral Laboratory, Department of Neurology, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20270-901, Brazil
- Gastroenterology & Liver Unit, Gaffrée e Guinle University Hospital, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20270-901, Brazil
| | - Max K Fakoury
- Postgraduate Program in Neurology, Neurobehavioral Laboratory, Department of Neurology, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20270-901, Brazil
- Gastroenterology & Liver Unit, Gaffrée e Guinle University Hospital, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20270-901, Brazil
- Internal Medicine Department, Gaffrée e Güinle University Hospital, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20270-901, Brazil
| | - Hellen Salazar
- Postgraduate Program in Neurology, Neurobehavioral Laboratory, Department of Neurology, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20270-901, Brazil
| | - Silvia B De Oliveira
- Postgraduate Program in Neurology, Neurobehavioral Laboratory, Department of Neurology, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20270-901, Brazil
| | - Carlos Eduardo Brandão-Mello
- Postgraduate Program in Neurology, Neurobehavioral Laboratory, Department of Neurology, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20270-901, Brazil
- Gastroenterology & Liver Unit, Gaffrée e Guinle University Hospital, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20270-901, Brazil
- Internal Medicine Department, Gaffrée e Güinle University Hospital, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20270-901, Brazil
| | - Sergio L Schmidt
- Postgraduate Program in Neurology, Neurobehavioral Laboratory, Department of Neurology, Federal University of the State of Rio de Janeiro, Rio de Janeiro 20270-901, Brazil
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Gutiérrez-Rojas L, de la Gándara Martín JJ, García Buey L, Uriz Otano JI, Mena Á, Roncero C. Patients with severe mental illness and hepatitis C virus infection benefit from new pangenotypic direct-acting antivirals: Results of a literature review. GASTROENTEROLOGIA Y HEPATOLOGIA 2023; 46:382-396. [PMID: 35718017 DOI: 10.1016/j.gastrohep.2022.06.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 05/25/2022] [Accepted: 06/07/2022] [Indexed: 05/09/2023]
Abstract
INTRODUCTION Hepatitis C virus (HCV) infection is a global health problem that can results in cirrhosis, hepatocellular carcinoma and even death. HCV infection is 3-20-fold more prevalent among patients with versus without severe mental illness (SMI), such as major depressive disorder, personality disorder, bipolar disorder and schizophrenia. Treatment options for HCV were formerly based on pegylated interferon alpha, which is associated with neuropsychiatric adverse events, and this contributed to the exclusion of patients with SMI from HCV treatment, elimination programmes, and clinical trials. Moreover, the assumption of poor adherence, scant access to healthcare and the stigma and vulnerability of this population emerged as barriers and contributed to the low rates of treatment and efficacy. METHODS This paper reviews the literature published between December 2010 and December 2020 exploring the epidemiology of HCV in patients with SMI, and vice versa, the effect of HCV infection, barriers to the management of illness in these patients, and benefits of new therapeutic options with pangenotypic direct antiviral agents (DAAs). RESULTS The approval of DAAs has changed the paradigm of HCV infection treatment. DAAs have proven to be an equally efficacious and safe option that improves quality of life (QoL) in patients SMI. CONCLUSIONS Knowledge of the consequences of the HCV infection and the benefits of treatment with new pangenotypic DAAs among psychiatrists can increase screening, referral and treatment of HCV infection in patients with SMI.
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Affiliation(s)
| | | | - Luisa García Buey
- Gastroenterology Department, Liver Unit, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, Madrid, Spain
| | - Juan I Uriz Otano
- Gastroenterology Department, Liver Unit, Complejo Hospitalario de Navarra, Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain
| | - Álvaro Mena
- Infectious Diseases Unit, Internal Medicine Service, Clinical Virology Group, Instituto de Investigación Biomédica de A Coruña (INIBIC)-Complejo Hospitalario Universitario de A Coruña (CHUAC), Universidade da Coruña, Coruña, Spain
| | - Carlos Roncero
- Psychiatry Service, University of Salamanca Health Care Complex and Psychiatric Unit, School of Medicine, Institute of Biomedicine, University of Salamanca, Salamanca, Spain
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Carvalho TL, Mertens Brainer de Queiroz Lima AC, de Araújo NS, de Sousa Fernandes MS, Lira GB, de Melo MMM, Vasconcelos LRS, de Moura PMMF, da Cunha Correia C. Aspects of cognitive assessments and spectroscopic magnetic resonance imaging in people with chronic hepatitis C: a systematic review. PSYCHOL HEALTH MED 2023; 28:1013-1029. [PMID: 35075963 DOI: 10.1080/13548506.2022.2029915] [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: 10/19/2022]
Abstract
Extrahepatic manifestations are common in people with hepatitis C virus (HCV). Cognitive changes are pointed out, but the mechanisms are still uncertain. The aim of this systematic review was to analyze studies involving spectroscopic magnetic resonance in people infected with HCV, which also included cognitive tests. The research occurred in six databases (Directory of Open Access Journals, Lilacs, Medcaribe, Medline, Scielo and ScienceDirect) and the selection of studies was carried out in two stages: search for titles and abstracts, then reading of the full articles, excluding those that did not meet the eligibility criteria. 12,888 titles and abstracts were selected, but only 6 articles were included in the review. Impairments in attention, concentration, speed of information processing, memory, verbal fluency and executive functions were identified as well as an increase in the Cho/Cr and mI/Cr ratios and a reduction in the NAA/Cr ratio in some included studies. Longitudinal studies, with more homogeneous samples and methods, as well as with better controlled confounding factors, are necessary to adequately identify the effect of HCV on the brain.
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Affiliation(s)
- Tatiana Lins Carvalho
- Hospital Universitário Oswaldo Cruz, Pós-Graduação em Ciências da Saúde, Universidade de Pernambuco (UPE), Recife, Brazil
| | | | | | - Matheus Santos de Sousa Fernandes
- Departamento de Fisiologia e Farmacologia, Pós-graduação Em Neuropsiquiatria e Ciências do Comportamento, Universidade Federal de Pernambuco (UFPE), Recife, Brazil
| | - Gabriela Barza Lira
- Programa de Pós-graduação de Saúde da Criança e do Adolescente, Universidade Federal de Pernambuco (UFPE), Recife, PE, Brazil
| | | | | | | | - Carolina da Cunha Correia
- Professor of Neurology and Post Graduate Course in Health Sciences, Universidade de Pernambuco (UPE), Recife, PE, Brazil
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Ghosh A, Mahintamani T, Rana DK, Basu D, Mattoo SK, Premkumar M, Singh GK. Neurocognitive Functions in Patients with Comorbid Hepatitis C and Opioid Dependence: A Comparative Study. Indian J Psychol Med 2023; 45:146-154. [PMID: 36925501 PMCID: PMC10011847 DOI: 10.1177/02537176221127449] [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: 11/16/2022] Open
Abstract
Background Hepatitis C virus (HCV) infection is commonly comorbid with opioid dependence (OD). We wanted to compare the neurocognitive functions of OD subjects with or without HCV [HCV (+), HCV (-)] and healthy controls (HC). Methods We recruited 40 adult subjects (age 18-55 years) in each group. HCV(+) group had a detectable viral load. Subjects with HIV or hepatitis B infection, head injury, epilepsy, or comorbid mental illness were excluded. We administered Standard Progressive Matrices (SPM), Wisconsin Card Sorting Test, Iowa Gambling Task (IGT), trail-making tests A and B, and verbal and visual N-back tests (NBT) one week after opioid abstinence. The group differences in cognitive performance were adjusted for age and years of education. Effect size (ES) is expressed as Cohen's D. Results The HCV(+) and HCV(-) groups did not differ in potential effect modifiers (age and years of education) or confounders (age of opioid initiation, duration of use, dependence severity, tobacco use, and cannabis use) of neuropsychological functioning. HCV(+) showed significantly poorer performance than HCV(-) in SPM (P = 0.006; ES = 0.72). Both HCV(+) and HCV(-) performed worse than controls in IGT(P < 0.001; ES = 0.8) and visual NBT[P < 0.01 and ES > 1 for total errors]; HCV(+) had a larger ES of group difference than HCV(-). HCV(+) had higher error scores in verbal NBT than control. Conclusion HCV(+) has poorer general intellectual ability and reasoning than HCV(-) persons and controls. Chronic HCV infection causes a higher magnitude of dysfunction in decision-making and visual working memory in opioid-dependent individuals.
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Affiliation(s)
- Abhishek Ghosh
- Drug Deaddiction and Treatment Centre & Dept. of Psychiatry, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Tathagata Mahintamani
- Lokopriya Gopinath Bordoloi Regional Institute of Mental Health, Tezpur, Assam, India
| | - Devender K Rana
- Drug Deaddiction and Treatment Centre & Dept. of Psychiatry, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Debasish Basu
- Drug Deaddiction and Treatment Centre & Dept. of Psychiatry, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | | | - Madhumita Premkumar
- Dept. of Hepatology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Geetesh Kumar Singh
- National Institute of Mental Health and Neuro-Sciences, Bangalore, Karnataka, India
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Shehata GA, Ahmed GK, Hassan EA, Rehim ASEDA, Mahmoud SZ, Masoud NA, Seifeldein GS, Hassan WA, Aboshaera KO. Impact of direct-acting antivirals on neuropsychiatric and neurocognitive dysfunction in chronic hepatitis C patients. THE EGYPTIAN JOURNAL OF NEUROLOGY, PSYCHIATRY AND NEUROSURGERY 2022. [DOI: 10.1186/s41983-022-00568-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
Abstract
Abstract
Background
Hepatitis C virus (HCV) infection is associated with psychiatric and cognitive dysfunctions. We aimed to investigate depression, anxiety, and cognitive function of chronic hepatitis C (CHC) patients before and after treatment with direct-acting antivirals (DAAs). Forty CHC patients (20 non-cirrhotic and 20 cirrhotic) who had undergone DAA treatment in our outpatient clinic and ten controls. We administered the Hospital Anxiety and Depression questionnaires to measure the anxiety and depression symptoms and the Cognitive Abilities Screening Instruments (CASI) to measure the cognitive function at the beginning and 3 months after the end of the treatment.
Results
Sustained virological response (SVR) was achieved in all patients. Post-treatment anxiety and depression scores showed a significant improvement than pre-treatment ones in CHC patients. Regarding CASI, before and after the treatment, a statistical significance was found in short-term memory (P = 0.001), concentration (P = 0.033), abstract thinking and judgment (P = 0.024), total (P = 0.001) in non-cirrhotic, Also, an improvement was seen in long-term memory (P = 0.015), short-term memory (P < 0.001), concentration (P = 0.024) and total (P = 0.01) in cirrhotic. However, these changes were still impaired in post-treated cirrhotic compared to controls.
Conclusions
CHC patients' anxiety, depression, and cognitive function partially improved after DAA therapy. Besides, improving the status of CHC, reversibility of cognitive dysfunction in non-cirrhotic patients may indicate the importance of treatment in early stages of liver disease.
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11
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Tan CH, Chang MC, Tsai WF, Chuang WL, Huang JF, Lin ZY, Dai CY, Yeh ML, Li CT, Yu RL. Different profiles of neurocognitive impairment in patients with hepatitis B and C virus infections. Sci Rep 2022; 12:10625. [PMID: 35739162 PMCID: PMC9226189 DOI: 10.1038/s41598-022-14736-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Accepted: 06/13/2022] [Indexed: 11/20/2022] Open
Abstract
The direct impact of chronic hepatitis B and hepatitis C on neurocognition remains elusive due to the frequent comorbidities, and the domains of the neurocognitive functions affected have rarely been investigated comprehensively. We cross-sectionally assessed the neurocognitive functions of the individuals with chronic hepatitis B, chronic hepatitis C, treated chronic hepatitis C with a sustained virologic response, and their healthy control counterparts. Laboratory examinations were used to investigate the impact of inflammation on neurocognition, exclude the medical conditions that could interfere with neurocognition assessment, and assess liver function and fibrotic severity of the liver of the participants. This study found the detrimental impact of chronic hepatitis B on language and executive functions. In contrast, individuals with chronic hepatitis C showed deficits in executive functions, psychomotor speed, memory, and attention. Successful elimination of hepatitis C resulted in improved liver function, but not neuropsychological test performance. Moreover, erythrocyte sedimentation rate level was found to mediate the deficits in the attention of individuals with chronic hepatitis C. These results demonstrate the neurocognitive deficits and the difference in the profiles of neurocognitive deficits in individuals with chronic hepatitis B and chronic hepatitis C. Our study also provided results suggesting the mediation by systemic inflammation on the attention deficit in individuals with chronic hepatitis C.
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Affiliation(s)
- Chun-Hsiang Tan
- Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Meng-Chia Chang
- Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Wei-Fang Tsai
- M.Sc. Program in Tropical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Zu-Yau Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chi-Ting Li
- Department of Psychology, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Rwei-Ling Yu
- Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
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12
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Shirley K, Loftis JM. A spotlight on HCV and SARS-CoV-2 co-infection and brain function. Pharmacol Biochem Behav 2022; 217:173403. [PMID: 35561837 PMCID: PMC9088049 DOI: 10.1016/j.pbb.2022.173403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 04/26/2022] [Accepted: 05/05/2022] [Indexed: 12/09/2022]
Affiliation(s)
- Kate Shirley
- Research & Development Service, VA Portland Health Care System, Portland, OR, USA; Department of Psychiatry, Oregon Health & Science University, Portland, OR, USA; Clinical Psychology PhD Program, Oregon Health & Science University, Portland, OR, USA
| | - Jennifer M Loftis
- Research & Development Service, VA Portland Health Care System, Portland, OR, USA; Department of Psychiatry, Oregon Health & Science University, Portland, OR, USA; Clinical Psychology PhD Program, Oregon Health & Science University, Portland, OR, USA; Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA.
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13
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Takaura K, Kurosaki M, Inada K, Kirino S, Yamashita K, Muto T, Osawa L, Sekiguchi S, Hayakawa Y, Higuchi M, Kaneko S, Maeyashiki C, Tamaki N, Yasui Y, Itakura J, Tsuchiya K, Nakanishi H, Takahashi Y, Izumi N. The impact of background liver disease on the long-term prognosis of very-early-stage HCC after ablation therapy. PLoS One 2022; 17:e0264075. [PMID: 35196341 PMCID: PMC8865683 DOI: 10.1371/journal.pone.0264075] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Accepted: 02/02/2022] [Indexed: 12/24/2022] Open
Abstract
Background and aim The long-term prognosis of hepatocellular carcinoma (HCC) treated at a very-early-stage (the Barcelona Clinical Liver Cancer (BCLC) classification stage 0) was unclear, especially in terms of background liver disease. Methods This single-center, retrospective study included 302 patients with BCLC stage 0 HCC treated with radiofrequency ablation (RFA) and followed for at least six months. We examined the impact of background liver disease on overall survival and recurrence. Results The median age was 72 (range; 36–91) years; the median tumor diameter was 15 (range; 8–20) mm. The etiologies of background liver disease were hepatitis B virus infection (HBV) in 24 cases, hepatitis C virus infection (HCV) in 195 cases, and non-viral (NBNC) in 83 cases. Among the patients with HCV, 63 had achieved sustained virological response (SVR) by antiviral therapy (HCV SVR) before developing HCC (n = 37) or after HCC treatment (n = 26), and 132 had active HCV infection (HCV non-SVR). The median overall survival was 85 (95% CI; 72–98) months, and the median recurrence-free survival was 26 (95% CI; 20–30) months. Active infection with hepatitis C virus negatively contributed to overall survival (HR 2.91, 95% CI 1.31–3.60, p = 0.003) and recurrence-free survival (HR 1.47, 95% CI 1.06–2.05, p = 0.011). Conclusions The prognosis of RFA treatment for very early-stage HCC was favorable. Achieving SVR in hepatitis C was important for further prognosis improvement.
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Affiliation(s)
- Kenta Takaura
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Kento Inada
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Sakura Kirino
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Kouji Yamashita
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Tomohiro Muto
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Leona Osawa
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Shuhei Sekiguchi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yuka Hayakawa
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Mayu Higuchi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Shun Kaneko
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Chiaki Maeyashiki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Nobuharu Tamaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
- Division of Medicine, NAFLD Research Center, University of California, San Diego, La Jolla, California, United States of America
| | - Yutaka Yasui
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Jun Itakura
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Kaoru Tsuchiya
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Hiroyuki Nakanishi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yuka Takahashi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
- * E-mail:
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14
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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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15
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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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16
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Ibáñez-Samaniego L, Rapado-Castro M, Cabrero L, Navarrete C, García-Mulas S, Ahumada A, Marquez L, Pérez MD, Rincon D, Bañares R, Garcia-Martinez R. Hepatitis C eradication improves cognitive function in patients with or without cirrhosis: A prospective real-life study. Eur J Neurol 2021; 29:400-412. [PMID: 34634159 DOI: 10.1111/ene.15138] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 10/05/2021] [Accepted: 10/07/2021] [Indexed: 01/23/2023]
Abstract
BACKGROUND AND PURPOSE Hepatitis C virus (HCV) infection is associated with neuropsychiatric disturbances that impact on functioning and health-related quality of life (HRQoL). Reversibility at different liver disease stages is unknown, particularly in cirrhosis. We aimed to evaluate cognition, functioning, and HRQoL following HCV eradication at different liver disease stages. METHODS A random sample (n = 152) of consecutive patients treated with direct-acting antiviral agents (DAAs) between April 2015 and March 2017 were included. A comprehensive neuropsychological assessment, functioning and HRQoL questionnaires were applied at baseline, and 12 and 48 weeks after the end of antivirals. RESULTS One-hundred thirty-five patients who achieved virological response completed the follow-up, of whom 44 had cirrhosis (27% decompensated). Twenty-one percent had cognitive impairment before starting DAAs (34.1% cirrhotic vs. 14.4% noncirrhotic, p < 0.011). Viral eradication was associated with a decrease in cognitive impairment to 23% of cirrhotic and 6% of noncirrhotic patients (p < 0.05). Interestingly, older patients (B = 0.11, 95% confidence interval [CI] = 0.03-0.19) with baseline cognitive impairment (B = 3.58, 95% CI = 1.54-5.62) were those with higher cognitive benefit, regardless of liver disease. Persistent cognitive impairment was associated with having higher cardiovascular risk, cirrhosis, lower education, and higher anxiety and depression scores. Functioning and HRQoL also improved after eradication but remained worse in the cirrhotic group. CONCLUSIONS Viral eradication decreases the prevalence of cognitive impairment and improves functioning and HRQoL. Patients with lower brain reserve (older patients) and baseline cognitive impairment may benefit the most. Identification and treatment of HCV patients through screening programs may reduce the burden of cognitive disturbances beyond the prevention of liver disease progression.
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Affiliation(s)
- Luis Ibáñez-Samaniego
- Hepatology Unit, Department of Digestive Diseases, Gregorio Marañón University General Hospital, Madrid, Spain.,Gregorio Marañón Institute of Health Research, Madrid, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain
| | - Marta Rapado-Castro
- Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Gregorio Marañón University General Hospital, Madrid, Spain.,Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne & Melbourne Health, Carlton, Victoria, Australia.,School of Medicine, Complutense University of Madrid, Madrid, Spain
| | - Lucia Cabrero
- Gregorio Marañón Institute of Health Research, Madrid, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain
| | - Cristina Navarrete
- Hepatology Unit, Department of Digestive Diseases, Gregorio Marañón University General Hospital, Madrid, Spain
| | - Seila García-Mulas
- Hepatology Unit, Department of Digestive Diseases, Gregorio Marañón University General Hospital, Madrid, Spain
| | - Adriana Ahumada
- Hepatology Unit, Department of Digestive Diseases, Gregorio Marañón University General Hospital, Madrid, Spain
| | - Laura Marquez
- Hepatology Unit, Department of Digestive Diseases, Gregorio Marañón University General Hospital, Madrid, Spain
| | - Maria Dolores Pérez
- Hepatology Unit, Department of Digestive Diseases, Gregorio Marañón University General Hospital, Madrid, Spain
| | - Diego Rincon
- Hepatology Unit, Department of Digestive Diseases, Gregorio Marañón University General Hospital, Madrid, Spain.,Gregorio Marañón Institute of Health Research, Madrid, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain.,School of Medicine, Complutense University of Madrid, Madrid, Spain
| | - Rafael Bañares
- Hepatology Unit, Department of Digestive Diseases, Gregorio Marañón University General Hospital, Madrid, Spain.,Gregorio Marañón Institute of Health Research, Madrid, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain.,School of Medicine, Complutense University of Madrid, Madrid, Spain
| | - Rita Garcia-Martinez
- Gregorio Marañón Institute of Health Research, Madrid, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain.,School of Medicine, Complutense University of Madrid, Madrid, Spain.,Department of Internal Medicine, Gregorio Marañon University General Hospital, Madrid, Spain
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17
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Choi HG, Soh JS, Lim JS, Sim SY, Lee SW. Association between dementia and hepatitis B and C virus infection. Medicine (Baltimore) 2021; 100:e26476. [PMID: 34398003 PMCID: PMC8294892 DOI: 10.1097/md.0000000000026476] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Revised: 05/06/2021] [Accepted: 06/07/2021] [Indexed: 01/04/2023] Open
Abstract
ABSTRACT Several viral infections are known to increase the risk of dementia through brain cell damage and systemic infection. The association between hepatitis B and C virus (HBV and HCV) infections and dementia was evaluated using a national sample cohort from South Korea. Using the national cohort study from the Korean National Health Insurance Service, we extracted data for patients with HBV or HCV infection and for matched control participants. The controls were matched to the patients according to age, sex, income, region of residence, and past medical histories. The incidence of HCV infection was higher in the dementia group (1.0% [113/11,228]) than in the control group (0.8% [364/44,912], P = .043). However, there was no difference in the incidence of HBV infection in the dementia and control groups. The adjusted odds ratio (OR) for HCV infection was 1.25 (95% confidence interval [CI] = 1.01-1.54, P = .043) in the dementia group. According to the subgroup analysis by sex, the adjusted ORs for HCV infection were 1.04 (95% CI = 072-1.49, P = .851) in men and 1.38 (95% CI = 1.06-1.79, P = .016) in women. We concluded that the incidence of HCV infection was higher (with a higher OR) in women with dementia than in matched control participants in South Korea.
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Affiliation(s)
- Hyo Geun Choi
- Department of Otorhinolaryngology-Head & Neck Surgery, Hallym University College of Medicine, Anyang, Republic of Korea
- Hallym Data Science Laboratory, Hallym University College of Medicine, Anyang, Republic of Korea
| | - Jae Seung Soh
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea
| | - Jae Sung Lim
- Department of Neurology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea
| | - Song Yong Sim
- Department of Statistics and Institute of Statistics, Hallym University, Chuncheon, Republic of Korea
| | - Suk Woo Lee
- Department of Obstetrics and Gynecology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea
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18
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Bar N, Levy S, Deutsch L, Leshno M, Rabinowich L, Younis F, Shibolet O, Katchman H. Hepatitis C related cognitive impairment: Impact of viral and host factors and response to therapy. J Viral Hepat 2021; 28:870-877. [PMID: 33624351 DOI: 10.1111/jvh.13492] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2020] [Revised: 02/06/2021] [Accepted: 02/13/2021] [Indexed: 01/06/2023]
Abstract
Chronic hepatitis C virus (HCV) infection is associated with cognitive impairment via several suggested mechanisms including direct neurotoxicity and minimal hepatic encephalopathy. The prevalence of HCV-related cognitive impairment and whether it is reversed by anti-viral therapy is unknown. We aimed to assess predictors and reversibility of cognitive impairment of HCV-infected patients after successful treatment. Consecutive HCV patients treated during the EMERALD study (AbbVie 3D regimen for protease inhibitors failure) underwent neuropsychological (number connection test A [NCTA] and digital symbol test [DST]) and neurophysiological (critical flicker frequency [CFF]) tests at baseline and at 12 weeks post-treatment. Patient self-reported outcomes (PROs) were prospectively collected. Patients with a history of hepatic encephalopathy were excluded. Thirty-two patients underwent the cognitive tests at baseline. Seven of them had abnormal CFF test findings. Twenty-five (25/32, 78%) patients had repeated evaluations 3 months post-treatment. High viral loads were significantly associated with abnormal CFF across fibrosis levels (area under the ROC curve 0.817). CFF results significantly improved following viral eradication, from 40.9 (interquartile range 38.6-42.9) at baseline to 41.5 (39.8-44), p = .042, at follow-up. Both NCTA and DST results improved, but not significantly. There was improvement in the PROs of general health perception and vitality. The NCTA and DST results were more significantly associated with PROs than CFF. This prospective interventional study showed greater cognitive impairment in HCV patients with high viral load and demonstrated partial reversibility of HCV neurotoxicity and subsequent improvement in PROs following treatment.
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Affiliation(s)
- Nir Bar
- Department of Gastroenterology and Hepatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Sharon Levy
- Department of Gastroenterology and Hepatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Liat Deutsch
- Department of Gastroenterology and Hepatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Moshe Leshno
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,The Coller School of Management, Tel Aviv University, Tel Aviv, Israel
| | - Liane Rabinowich
- Department of Gastroenterology and Hepatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Fadi Younis
- Department of Gastroenterology and Hepatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Oren Shibolet
- Department of Gastroenterology and Hepatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Helena Katchman
- Department of Gastroenterology and Hepatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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19
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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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Tassi A, Gitto S, Piras C, Cursaro C, Alicandro T, Margotti M, Rivi M, Andreone P. Cognitive, neurological and psychiatric disorders occurring in Hepatitis C Virus infection. Minerva Med 2021; 112:238-245. [PMID: 33576202 DOI: 10.23736/s0026-4806.21.07388-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Chronic Hepatitis C is associated with many extrahepatic manifestations. Central nervous system is frequently involved, but the pathophysiological mechanisms are not fully understood. Local and systemic inflammation, ischemia, immune-mediated phenomena have been described in this context. Clinical manifestations include cognitive alterations, stroke, depression and demyelinating phenomena. It is unclear if cognitive deficits can be improved or resolved with viral eradication and to understand this, could have important therapeutical implications.
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Affiliation(s)
- Andrea Tassi
- Division of Internal Medicine, Department of Medical and Surgical Sciences, Maternal-Infantile and Adult, University of Modena and Reggio Emilia, Modena, Italy
| | - Stefano Gitto
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Chiara Piras
- Graduating School of Medicine and Surgery, University of Modena and Reggio Emilia, Modena, Italy
| | - Carmela Cursaro
- Division of Internal Medicine, Department of Medical and Surgical Sciences, Maternal-Infantile and Adult, University of Modena and Reggio Emilia, Modena, Italy
| | - Tatiana Alicandro
- Division of Internal Medicine, Department of Medical and Surgical Sciences, Maternal-Infantile and Adult, University of Modena and Reggio Emilia, Modena, Italy
- Postgraduate School of Allergy and Clinical Immunology, University of Modena and Reggio Emilia, Modena, Italy
| | - Marzia Margotti
- Division of Internal Medicine, Department of Medical and Surgical Sciences, Maternal-Infantile and Adult, University of Modena and Reggio Emilia, Modena, Italy
| | - Marco Rivi
- Division of Internal Medicine, Department of Medical and Surgical Sciences, Maternal-Infantile and Adult, University of Modena and Reggio Emilia, Modena, Italy
- Postgraduate School of Allergy and Clinical Immunology, University of Modena and Reggio Emilia, Modena, Italy
| | - Pietro Andreone
- Division of Internal Medicine, Department of Medical and Surgical Sciences, Maternal-Infantile and Adult, University of Modena and Reggio Emilia, Modena, Italy -
- Postgraduate School of Allergy and Clinical Immunology, University of Modena and Reggio Emilia, Modena, Italy
- Unit of Internal and Metabolic Medicine, Civil Hospital of Baggiovara, University of Modena and Reggio Emilia, Baggiovara, Modena, Italy
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Salmani H, Hosseini M, Baghcheghi Y, Samadi-Noshahr Z. The brain consequences of systemic inflammation were not fully alleviated by ibuprofen treatment in mice. Pharmacol Rep 2021; 73:130-142. [PMID: 32696348 DOI: 10.1007/s43440-020-00141-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Revised: 07/13/2020] [Accepted: 07/15/2020] [Indexed: 01/02/2023]
Abstract
BACKGROUND Extensive data point to the immune system as an important factor underlying the pathogenesis of brain diseases. Epidemiological studies have shown that long-term treatment with non-steroidal anti-inflammatory drugs (NSAIDs) significantly reduces the onset and progression of Alzheimer's disease. The present study aimed to investigate whether ibuprofen (IBU) is able to prevent the long-lasting alterations of brain function induced by systemic inflammation. METHODS Mice received intraperitoneal injections of lipopolysaccharide (LPS; 250 µg/kg/day) for seven consecutive days. Ibuprofen administration (40 mg/kg/day) was started three days before the LPS injections and continued until the last day of LPS injection. Within the next 2 weeks, mice performances on the behavioral tests were evaluated, and then brain tissue samples for biochemical analyses were collected. RESULTS The findings showed that ibuprofen significantly improved mice's performance in the passive avoidance test and reduced anxiety- and depressive-like behaviors. However, ibuprofen could not significantly improve spatial memory in the Morris water maze test and recognition ability in the novel object recognition test. TNF-α and IL-1β cytokines levels and malondialdehyde (MDA) concentration in the hippocampal tissues of LPS-treated mice were significantly lowered by ibuprofen treatment, whereas no significant effects on IL-10 production and hippocampal BDNF levels were observed. In addition, ibuprofen did not significantly reduce amyloid-β1-40 levels in the hippocampus of LPS-treated animals. CONCLUSION Overall, the findings of the present study suggest that some, but not all, of the adverse effects of systemic inflammation are alleviated by ibuprofen treatment.
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Affiliation(s)
- Hossein Salmani
- Student Research Committee, Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Division of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahmoud Hosseini
- Division of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
- Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
- Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Yousef Baghcheghi
- Student Research Committee, Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Zahra Samadi-Noshahr
- Student Research Committee, Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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Britton MK, Porges EC, Bryant V, Cohen RA. Neuroimaging and Cognitive Evidence for Combined HIV-Alcohol Effects on the Central Nervous System: A Review. Alcohol Clin Exp Res 2021; 45:290-306. [PMID: 33296091 PMCID: PMC9486759 DOI: 10.1111/acer.14530] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Accepted: 11/29/2020] [Indexed: 12/27/2022]
Abstract
Alcohol use disorder (AUD) among people living with HIV (PLWH) is a significant public health concern. Despite the advent of effective antiretroviral therapy, up to 50% of PLWH still experience worsened neurocognition, which comorbid AUD exacerbates. We report converging lines of neuroimaging and neuropsychological evidence linking comorbid HIV/AUD to dysfunction in brain regions linked to executive function, learning and memory, processing speed, and motor control, and consequently to impairment in daily life. The brain shrinkage, functional network alterations, and brain metabolite disruption seen in individuals with HIV/AUD have been attributed to several interacting pathways: viral proteins and EtOH are directly neurotoxic and exacerbate each other's neurotoxic effects; EtOH reduces antiretroviral adherence and increases viral replication; AUD and HIV both increase gut microbial translocation, promoting systemic inflammation and HIV transport into the brain by immune cells; and HIV may compound alcohol's damaging effects on the liver, further increasing inflammation. We additionally review the neurocognitive effects of aging, Hepatitis C coinfection, obesity, and cardiovascular disease, tobacco use, and nutritional deficiencies, all of which have been shown to compound cognitive changes in HIV, AUD, and in their comorbidity. Finally, we examine emerging questions in HIV/AUD research, including genetic and cognitive protective factors, the role of binge drinking in HIV/AUD-linked cognitive decline, and whether neurocognitive and brain functions normalize after drinking cessation.
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Affiliation(s)
- Mark K. Britton
- University of Florida, Department of Clinical and Health Psychology, Center for Cognitive Aging and Memory, Cognitive Aging and Memory Clinical Translational Research Program; 1225 Center Drive, Gainesville, Florida 32607
| | - Eric C. Porges
- University of Florida, Department of Clinical and Health Psychology, Center for Cognitive Aging and Memory, Cognitive Aging and Memory Clinical Translational Research Program; 1225 Center Drive, Gainesville, Florida 32607
| | - Vaughn Bryant
- University of Florida, Department of Clinical and Health Psychology, Center for Cognitive Aging and Memory, Cognitive Aging and Memory Clinical Translational Research Program; 1225 Center Drive, Gainesville, Florida 32607
- University of Florida, Department of Epidemiology, 2004 Mowry Road, Gainesville, FL 32610
| | - Ronald A. Cohen
- University of Florida, Department of Clinical and Health Psychology, Center for Cognitive Aging and Memory, Cognitive Aging and Memory Clinical Translational Research Program; 1225 Center Drive, Gainesville, Florida 32607
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Ochi H, Hiraoka A, Hirooka M, Koizumi Y, Amano M, Azemoto N, Watanabe T, Yoshida O, Tokumoto Y, Mashiba T, Yokota T, Abe M, Michitaka K, Hiasa Y, Joko K. Direct-acting antivirals improve survival and recurrence rates after treatment of hepatocellular carcinoma within the Milan criteria. J Gastroenterol 2021; 56:90-100. [PMID: 33278003 PMCID: PMC7819935 DOI: 10.1007/s00535-020-01747-y] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Accepted: 10/29/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND The effects of direct-acting antivirals (DAAs) on survival and recurrence rates after curative hepatocellular carcinoma (HCC) treatment in patients with hepatitis C virus (HCV) infection remain controversial. METHODS This retrospective, multicenter study involved Child-Pugh class A patients within the Milan criteria who had a first diagnosis of HCC and survived 6 months or longer after undergoing hepatectomy or radiofrequency ablation (RFA). The DAA-treated group (DAA group) included 56 patients, and the DAA-untreated group (untreated group) included 261 patients. The study was conducted using the propensity score-matched (1:2) DAA group and untreated group, 56 and 112 patients, respectively. RESULTS The survival rate at 48 months in the DAA group and the untreated group was 91.0% and 68.7%, respectively, showing significantly better survival in the DAA group (HR: 0.33; 95% CI 0.13-0.84; p = 0.021). The recurrence rate at 48 months was 36.7% and 66.7%, respectively, showing a significantly lower recurrence rate in the DAA group (HR, 0.46; 95% CI 0.27-0.77; p = 0.003). The median albumin-bilirubin (ALBI) score at 3 years post-HCC treatment was - 2.84 in the DAA group and - 2.34 in the untreated group. The ALBI score showed a significant improvement from baseline to 3 years post-HCC treatment (p = 0.001), whereas that in the untreated group showed a significant decline (p = 0.040). CONCLUSIONS DAAs after HCC treatment prevents deterioration of hepatic functional reserve and significantly improves both recurrence and survival rates.
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Affiliation(s)
- Hironori Ochi
- Center for Liver-Biliary-Pancreatic Disease, Matsuyama Red Cross Hospital, Bunkyo-cho 1, Matsuyama, Ehime Japan
| | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Kasuga-cho 83, Matsuyama, Ehime Japan
| | - Masashi Hirooka
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime Japan
| | - Yohei Koizumi
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime Japan
| | - Michiko Amano
- Center for Liver-Biliary-Pancreatic Disease, Matsuyama Red Cross Hospital, Bunkyo-cho 1, Matsuyama, Ehime Japan
| | - Nobuaki Azemoto
- Center for Liver-Biliary-Pancreatic Disease, Matsuyama Red Cross Hospital, Bunkyo-cho 1, Matsuyama, Ehime Japan
| | - Takao Watanabe
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime Japan
| | - Osamu Yoshida
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime Japan
| | - Yoshio Tokumoto
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime Japan
| | - Toshie Mashiba
- Center for Liver-Biliary-Pancreatic Disease, Matsuyama Red Cross Hospital, Bunkyo-cho 1, Matsuyama, Ehime Japan
| | - Tomoyuki Yokota
- Center for Liver-Biliary-Pancreatic Disease, Matsuyama Red Cross Hospital, Bunkyo-cho 1, Matsuyama, Ehime Japan
| | - Masanori Abe
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime Japan
| | - Kojiro Michitaka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Kasuga-cho 83, Matsuyama, Ehime Japan
| | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime Japan
| | - Kouji Joko
- Center for Liver-Biliary-Pancreatic Disease, Matsuyama Red Cross Hospital, Bunkyo-cho 1, Matsuyama, Ehime Japan
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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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Direct antivirals and cognitive impairment in hepatitis C: a clinical-neurophysiologic study. J Neurovirol 2020; 26:870-879. [PMID: 32910431 PMCID: PMC7716927 DOI: 10.1007/s13365-020-00904-6] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 08/05/2020] [Accepted: 08/26/2020] [Indexed: 12/26/2022]
Abstract
Cognition was assessed in hepatitis C virus (HCV) patients, who did not meet the criteria for a minimal hepatic encephalopathy. Their liver function was compensated. We then disentangled potential cognitive changes associated with a sustained virologic response at 12 weeks (SVR-12), following treatment with direct antiviral agents (DAAs). We studied 23 selected HCV patients with a battery of standard neuropsychological tests, and with recordings of the P300 wave, a cerebral potential of “cognitive” significance. There was a baseline evaluation (T0) and a second one 6 months later (T1). We had 2 control groups of comparable age and sex, i.e., 15 patients suffering from non-alcoholic fatty liver disease (NAFLD) and 15 healthy subjects. At T0, we detected a significant (p < 0.05) cognitive impairment in the HCV group, which involved episodic and working memory, attention, visuospatial and verbal abilities, executive functions, and logic reasoning. The P300 latency was significantly (p < 0.05) delayed in the group. At T1, we observed some significant (p < 0.05) HCV recovery in given test domains, e.g., memory, executive functions, and reasoning. Accordingly, the P300 latency shortened significantly (p < 0.05). HCV patients exhibited subtle cognitive defects, somehow independent of their liver condition, possibly linked to direct or indirect brain involvement by the virus. These defects partly recovered following the SVR-12, as achieved through DAAs. The P300 wave was a valid neurophysiologic counterpart of these changes. DAAs can have a role in the early preservation of cognition in HCVs.
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Luo M, Mu R, Liu JF, Bai FH. Novel computerized psychometric tests as primary screening tools for the diagnosis of minimal hepatic encephalopathy. World J Clin Cases 2020; 8:3377-3389. [PMID: 32913845 PMCID: PMC7457114 DOI: 10.12998/wjcc.v8.i16.3377] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Revised: 05/05/2020] [Accepted: 07/14/2020] [Indexed: 02/06/2023] Open
Abstract
Minimal hepatic encephalopathy (MHE) is a critical neurocognitive complication of decompensated liver cirrhosis and portosystemic shunting, which results in a wide range of cognitive deficits including impairments in working attention, psychomotor speed, and executive function. Current guidelines have recommended paper-and-pencil psychometric tests for the diagnosis of MHE. Most high-risk cirrhotic patients are required to be examined; however, paper-and-pencil psychometric tests are neither convenient nor rapid to perform in the clinic. Recently, novel computerized psychometric tests, including the inhibitory control test, EncephalApp Stroop App, and critical flicker frequency, have been proven to be rapid, effective, and convenient methods for screening MHE in clinical practice and for identifying high-risk cirrhotic patients for further validation using rigid neuropsychometric examinations. However, diagnostic accuracy of these tests is influenced by educational background, age, and cultural differences. This review summarizes clinical evidence of the application of novel computerized psychometric tests for screening MHE.
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Affiliation(s)
- Ming Luo
- Department of Gastroenterology, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan 750021, Ningxia Hui Autonomous Region, China
| | - Rui Mu
- Department of Gastroenterology, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan 750021, Ningxia Hui Autonomous Region, China
| | - Jian-Fang Liu
- Department of Gastroenterology, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan 750021, Ningxia Hui Autonomous Region, China
| | - Fei-Hu Bai
- Department of Gastroenterology, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan 750021, Ningxia Hui Autonomous Region, China
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The Many Difficulties and Subtleties in the Cognitive Assessment of Chronic Hepatitis C Infection. Int J Hepatol 2020; 2020:9675235. [PMID: 32257447 PMCID: PMC7106929 DOI: 10.1155/2020/9675235] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2019] [Revised: 02/27/2020] [Accepted: 03/10/2020] [Indexed: 12/30/2022] Open
Abstract
Since the discovery of HCV in 1989, several diseases have been related to chronic infection by this virus. Often, patients with hepatitis C virus (HCV) complain of cognitive impairment even before the development of hepatic cirrhosis, which they described as "brain fog." Several studies have proposed a link between chronic HCV infection and the development of cognitive alterations, but the inclusion of confounding factors in their samples significantly limits the analysis of the results. In this article, we will give an overview about cognitive dysfunction in patients with HCV.
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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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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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Modification of Serum Brain-Derived Neurotrophic Factor Levels Following Anti-HCV Therapy with Direct Antiviral Agents: A New Marker of Neurocognitive Disorders. HEPATITIS MONTHLY 2020. [DOI: 10.5812/hepatmon.95101] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
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Shiha G, Mousa N. Minimal Hepatic Encephalopathy: Silent Tragedy. LIVER DISEASE AND SURGERY [WORKING TITLE] 2019. [DOI: 10.5772/intechopen.88231] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/30/2024]
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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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33
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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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36
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Liver fibrosis is associated with cognitive impairment in people living with HIV. Infection 2019; 47:589-593. [PMID: 30784024 DOI: 10.1007/s15010-019-01284-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2018] [Accepted: 02/14/2019] [Indexed: 12/13/2022]
Abstract
PURPOSE Our aim was to better explore the association between liver fibrosis (LF) and neurocognitive impairment (NCI) in people living with HIV (PLWH). METHODS We performed a cross-sectional cohort study by consecutively enrolling PLWH at two clinical centers. All subjects underwent a comprehensive neuropsychological battery; NCI was defined as having a pathological performance (1.5 SD below the normative mean) on at least two cognitive domains. LF was explored using FIB4 index; in a subgroup of PLWH, LF was also assessed by transient elastography. RESULTS A total of 386 subjects were enrolled, of whom 17 (4.4%) had FIB4 > 3.25. In the subgroup of PLWH (N = 127) performing also liver transient elastography, 14 (11%) had liver stiffness > 14 kPa. Overall, 47 subjects (12%) were diagnosed with NCI. At multivariate regression analyses, participants with FIB4 > 1.45 showed a higher risk of NCI in comparison with those with lower values (aOR 3.04, p = 0.044), after adjusting for education (aOR 0.71, p < 0.001), past AIDS-defining events (aOR 2.91, p = 0.014), CD4 cell count, past injecting drug use (IDU), HIV-RNA < 50 copies/mL, and HCV co-infection. Also a liver stiffness > 14 kPa showed an independent association with a higher risk of NCI (aOR 10.13, p = 0.041). Analyzing any single cognitive domain, a higher risk of abnormal psychomotor speed was associated with a liver stiffness > 14 kPa (aOR 223.17, p = 0.019) after adjusting for education (aOR 0.57, p = 0.018), HIV-RNA < 50 copies/mL (aOR 0.01, p = 0.007), age, past IDU, and HCV co-infection. CONCLUSIONS In PLWH, increased LF, estimated through non-invasive methods, was associated to a higher risk of NCI independently from HCV status.
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37
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Liver Transplant Recipients Older Than 60 Years Show Executive and Memory Function Improvement Comparable to Younger Recipients. PSYCHOSOMATICS 2019; 60:488-498. [PMID: 30772017 DOI: 10.1016/j.psym.2019.01.008] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/26/2018] [Revised: 01/21/2019] [Accepted: 01/21/2019] [Indexed: 01/06/2023]
Abstract
BACKGROUND Increasing numbers of patients over the age of 60 are undergoing liver transplantation. OBJECTIVE We sought to determine whether age or clinical morbidities were associated with pre- and post-transplant executive and memory performance using the Brief Test of Adult Cognition by Telephone (BTACT). METHODS Participants included 36 recipients with n = 20 in the older group (>60 y) and n = 16 in the younger group (≤60 years). The BTACT was administered an average of 3 months before transplant, and at follow-up post-transplant intervals of 3, 6, and 9 months. BTACT composite scores for memory and executive function with age and education norms were obtained. RESULTS Older recipients were more likely to have hepatocellular carcinoma, a lower biological MELD score at transplant, less cellular rejection, and fewer post-operative hospital days. Older and younger recipients showed comparable pre-transplant executive and memory function and comparable post-transplant improvement. Both older and younger patients showed statistically significant improvement in executive function scores at 3 months post-transplant and maintained improvement at 6 and 9 months. Memory function improved significantly in older patients by 6 months post-transplant but did not improve significantly in the younger group. CONCLUSION Older liver transplant recipients were more likely to have hepatocellular carcinoma and a lower biological MELD score than younger recipients, but both age groups showed comparable pre-transplant cognitive performance and post-transplant cognitive improvement. Additionally, a normed telephone test can be used to effectively screen and track executive and memory function post-transplant.
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38
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Oriolo G, Egmond E, Mariño Z, Cavero M, Navines R, Zamarrenho L, Solà R, Pujol J, Bargallo N, Forns X, Martin-Santos R. Systematic review with meta-analysis: neuroimaging in hepatitis C chronic infection. Aliment Pharmacol Ther 2018. [PMID: 29536563 DOI: 10.1111/apt.14594] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Chronic hepatitis C is considered a systemic disease because of extra-hepatic manifestations. Neuroimaging has been employed in hepatitis C virus-infected patients to find in vivo evidence of central nervous system alterations. AIMS Systematic review and meta-analysis of neuroimaging research in chronic hepatitis C treatment naive patients, or patients previously treated without sustained viral response, to study structural and functional brain impact of hepatitis C. METHODS Using PRISMA guidelines a database search was conducted from inception up until 1 May 2017 for peer-reviewed studies on structural or functional neuroimaging assessment of chronic hepatitis C patients without cirrhosis or encephalopathy, with control group. Meta-analyses were performed when possible. RESULTS The final sample comprised 25 studies (magnetic resonance spectroscopy [N = 12], perfusion weighted imaging [N = 1], positron emission tomography [N = 3], single-photon emission computed tomography [N = 4], functional connectivity in resting state [N = 1], diffusion tensor imaging [N = 2] and structural magnetic resonance imaging [N = 2]). The whole sample was of 509 chronic hepatitis C patients, with an average age of 41.5 years old and mild liver disease. A meta-analysis of magnetic resonance spectroscopy studies showed increased levels of choline/creatine ratio (mean difference [MD] 0.12, 95% confidence interval [CI] 0.06-0.18), creatine (MD 0.85, 95% CI 0.42-1.27) and glutamate plus glutamine (MD 1.67, 95% CI 0.39-2.96) in basal ganglia and increased levels of choline/creatine ratio in centrum semiovale white matter (MD 0.13, 95% CI 0.07-0.19) in chronic hepatitis C patients compared with healthy controls. Photon emission tomography studies meta-analyses did not find significant differences in PK11195 binding potential in cortical and subcortical regions of chronic hepatitis C patients compared with controls. Correlations were observed between various neuroimaging alterations and neurocognitive impairment, fatigue and depressive symptoms in some studies. CONCLUSIONS Patients with chronic hepatitis C exhibit cerebral metabolite alterations and structural or functional neuroimaging abnormalities, which sustain the hypothesis of hepatitis C virus involvement in brain disturbances.
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Affiliation(s)
- G Oriolo
- Department of Psychiatry and Psychology, Hospital Clinic, Institut d'Investigació Biomèdica Arthur Pi I Sunyer (IDIBAPS), Centro Investigación Biomédica en Red de Salud Mental (CIBERSAM), University of Barcelona, Barcelona, Spain.,Department of Medicine, Institute of Neuroscience, University of Barcelona, Barcelona, Spain
| | - E Egmond
- Department of Psychiatry and Psychology, Hospital Clinic, Institut d'Investigació Biomèdica Arthur Pi I Sunyer (IDIBAPS), Centro Investigación Biomédica en Red de Salud Mental (CIBERSAM), University of Barcelona, Barcelona, Spain.,Department of Medicine, Institute of Neuroscience, University of Barcelona, Barcelona, Spain.,Department of Health and Clinical Psychology, Faculty of Psychology, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Z Mariño
- Liver Unit, Hospital Clinic, IDIBAPS, Centro Investigación Biomédica en Red de Enfermedades hepáticas y digestivas, (CIBEREHD), University of Barcelona, Barcelona, Spain
| | - M Cavero
- Department of Psychiatry and Psychology, Hospital Clinic, Institut d'Investigació Biomèdica Arthur Pi I Sunyer (IDIBAPS), Centro Investigación Biomédica en Red de Salud Mental (CIBERSAM), University of Barcelona, Barcelona, Spain.,Department of Medicine, Institute of Neuroscience, University of Barcelona, Barcelona, Spain
| | - R Navines
- Department of Psychiatry and Psychology, Hospital Clinic, Institut d'Investigació Biomèdica Arthur Pi I Sunyer (IDIBAPS), Centro Investigación Biomédica en Red de Salud Mental (CIBERSAM), University of Barcelona, Barcelona, Spain.,Department of Medicine, Institute of Neuroscience, University of Barcelona, Barcelona, Spain
| | - L Zamarrenho
- Departamento de Neurociências e Ciências do Comportamento, Faculdade de Medicina de Ribeirão Preto - Universidade de São Paulo (USP), Ribeirão Preto (SP), Brazil
| | - R Solà
- Liver Unit, Parc de Salut Mar, Universitat Autonoma de Barcelona, Barcelona, Spain
| | - J Pujol
- MRI Research Unit, Department of Radiology, Hospital del Mar, CIBERSAM, Barcelona, Spain
| | - N Bargallo
- Center of Diagnostic Image (CDIC), Hospital Clinic, Magnetic Resonance Image Core Facility, IDIBAPS, Barcelona, Spain
| | - X Forns
- Liver Unit, Hospital Clinic, IDIBAPS, Centro Investigación Biomédica en Red de Enfermedades hepáticas y digestivas, (CIBEREHD), University of Barcelona, Barcelona, Spain
| | - R Martin-Santos
- Department of Psychiatry and Psychology, Hospital Clinic, Institut d'Investigació Biomèdica Arthur Pi I Sunyer (IDIBAPS), Centro Investigación Biomédica en Red de Salud Mental (CIBERSAM), University of Barcelona, Barcelona, Spain.,Department of Medicine, Institute of Neuroscience, University of Barcelona, Barcelona, Spain.,Departamento de Neurociências e Ciências do Comportamento, Faculdade de Medicina de Ribeirão Preto - Universidade de São Paulo (USP), Ribeirão Preto (SP), Brazil
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Zahr NM. The Aging Brain With HIV Infection: Effects of Alcoholism or Hepatitis C Comorbidity. Front Aging Neurosci 2018; 10:56. [PMID: 29623036 PMCID: PMC5874324 DOI: 10.3389/fnagi.2018.00056] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2017] [Accepted: 02/20/2018] [Indexed: 12/11/2022] Open
Abstract
As successfully treated individuals with Human Immunodeficiency Virus (HIV)-infected age, cognitive and health challenges of normal aging ensue, burdened by HIV, treatment side effects, and high prevalence comorbidities, notably, Alcohol Use Disorders (AUD) and Hepatitis C virus (HCV) infection. In 2013, people over 55 years old accounted for 26% of the estimated number of people living with HIV (~1.2 million). The aging brain is increasingly vulnerable to endogenous and exogenous insult which, coupled with HIV infection and comorbid risk factors, can lead to additive or synergistic effects on cognitive and motor function. This paper reviews the literature on neuropsychological and in vivo Magnetic Resonance Imaging (MRI) evaluation of the aging HIV brain, while also considering the effects of comorbidity for AUD and HCV.
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Affiliation(s)
- Natalie M Zahr
- Neuroscience Program, SRI International, Menlo Park, CA, United States.,Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA, United States
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40
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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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Forton D, Weissenborn K, Bondin M, Cacoub P. Expert opinion on managing chronic HCV in patients with neuropsychiatric manifestations. Antivir Ther 2018; 23:47-55. [PMID: 30451150 DOI: 10.3851/imp3245] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/21/2018] [Indexed: 10/27/2022]
Abstract
Neurological manifestations of HCV infection appear to be under-recognized in clinical practice despite the majority of HCV-infected patients experiencing symptoms such as fatigue, depression and cognitive dysfunction. There is also growing evidence for a link between HCV infection and an increased risk of Parkinson's disease. The mechanism underpinning the association between HCV and these neuropsychiatric syndromes still requires further investigation. Here we review the pre-clinical and clinical evidence for a link between HCV and effects on the central nervous system leading to neuropsychiatric syndromes. Lastly, we describe how improvements in neuropsychiatric manifestations of HCV following treatment have been observed, which is subsequently reflected in an overall improvement in health-related quality of life.
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Affiliation(s)
- Daniel Forton
- Department of Gastroenterology and Hepatology, St George's Hospital London, London, UK
- St George's University of London, London, UK
| | | | | | - Patrice 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, F-75005, Paris, France
- AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
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42
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Barreira DP, Marinho RT, Bicho M, Fialho R, Ouakinin SRS. Psychosocial and Neurocognitive Factors Associated With Hepatitis C - Implications for Future Health and Wellbeing. Front Psychol 2018; 9:2666. [PMID: 30687151 PMCID: PMC6333630 DOI: 10.3389/fpsyg.2018.02666] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Accepted: 12/11/2018] [Indexed: 12/18/2022] Open
Abstract
Background: Hepatitis C virus (HCV) infection involves changes not only from the point of view of physical health, but also emotional, and social that have a significant impact on the quality of life of these patients. According to the literature review, it seems that there is an important association between psychosocial factors, in particular on a cognitive level and disease progression. The aim of this mini-review is to summarize recent literature looking at the associations between psychosocial and neurocognitive factors and HCV. Methods: PubMed/Medline was systematically searched for psychosocial and neurocognitive factors associated with hepatitis C, treatment adherence, and patient wellbeing. Results: Patients present with a range of extrahepatic symptoms including fatigue, anxiety, depression, and neurocognitive dysfunction. HCV's impact on quality of life and wellbeing has serious clinical and social implications. Conclusion: Hepatitis C and its management continue to have a profound impact on health and psychologic wellbeing. Considering the serious extrahepatic implications for individuals, it is imperative that healthcare professionals pay close attention to psychosocial and neurocognitive factors. The focus on combined clinical approaches could enhance understanding about the health and social impacts of hepatitis C along the life course.
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Affiliation(s)
- David Pires Barreira
- Clínica Universitária de Psiquiatria e Psicologia Médica, Faculdade de Medicina, Universidade de Lisboa, Serviço de Gastrenterologia e Hepatologia, Centro Hospitalar Lisboa Norte-Hospital de Santa Maria, Lisbon, Portugal
- *Correspondence: David Pires Barreira,
| | - Rui Tato Marinho
- Faculdade de Medicina, Universidade de Lisboa, Serviço de Gastrenterologia e Hepatologia, Centro Hospitalar Lisboa Norte-Hospital de Santa Maria, Lisbon, Portugal
| | - Manuel Bicho
- Laboratório de Genética, Faculdade de Medicina, Instituto de Saúde Ambiental, Universidade de Lisboa, Lisbon, Portugal
| | - Renata Fialho
- Assertive Outreach Team, Sussex Partnership NHS Foundation Trust, Brighton and Hove, United Kingdom
| | - Silvia Raquel Soares Ouakinin
- Clínica Universitária de Psiquiatria e Psicologia Médica, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
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43
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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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Kumar A, Deep A, Gupta RK, Atam V, Mohindra S. Brain Microstructural Correlates of Cognitive Dysfunction in Clinically and Biochemically Normal Hepatitis C Virus Infection. J Clin Exp Hepatol 2017; 7:198-204. [PMID: 28970706 PMCID: PMC5620352 DOI: 10.1016/j.jceh.2017.03.011] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2016] [Accepted: 03/14/2017] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND/AIMS This study examined correlates of the brain's neurocognitive performance among clinically and biochemically normal adult patient with hepatitis C virus (HCV). We hypothesized that anti-HCV positive individuals would demonstrate structural brain abnormalities and neurocognitive dysfunction as well as the changes in cell component and extracellular space in the white matter regions of brain in asymptomatic HCV infection by using diffusion tensor tractrography (DTT) metrics. METHODS Anti-HCV positive patient (n = 40), and healthy controls (n = 31), fulfilling inclusion criteria (incidentally detected anti-HCV positive) and able to provide informed consent were screened and recruited for the study. All these subjects and controls underwent subjective assessment of their quality of life related symptoms, neuropsychometric tests (NPT) and magnetic resonance imaging. RESULTS The patients were subjected to neuroimaging as well as psychological testing. There was no significant difference in basic laboratory parameters in these two groups. Independent t-test reveals significantly lower neuropsychological functioning as compared to healthy control. A significantly decreased FA values and myoinsitol were observed in HCV subjects on sensory, inferior longitudinal fascicules, and STR fiber bundles as compared to healthy control. Bivariate correlation analysis reveals that neuropsychological scores are significantly positive. CONCLUSION Our result show that HCV positive individuals would demonstrate structural brain abnormalities and neurocognitive dysfunction as well as the changes in cell component and extracellular space in the white matter regions of brain in asymptomatic HCV infection by using DTT metrics.
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Key Words
- BD, block design
- CC, central cortex
- Cho, choline
- DS, digit symbol
- DTT, diffusion tensor tractrography
- FA, fractional anisotrophy
- FCA, figure connection test A
- FCB, figure connection test B
- Gln, glutamine
- Glx, glutamate
- ILF, inferior longitudinal fascicules
- Ins, inositol
- MD, mean diffusivity
- MRI
- NAA, N-acetylaspartate
- OA, object assembly
- PA, picture arrangement
- PC, picture completion
- QOL, quality of life
- SLF, superior longitudinal fascicules
- STR fiber bundles
- STR, superior thalamic radiations
- hepatitis C virus
- myoinsitol
- neuropsychometric tests
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Affiliation(s)
- Ajay Kumar
- Department of Medical Gastroenterology, King George's Medical University, Lucknow 226003, India,Address for correspondence: Ajay Kumar, Assistant Prof, Department of Medical Gastroenterology, K.G. Medical University, Lucknow, UP 226003, India. Tel.: +91 9455519306.Department of Medical Gastroenterology, K.G. Medical UniversityLucknowUP226003India
| | - Amar Deep
- Department of Medical Gastroenterology, King George's Medical University, Lucknow 226003, India,Experimental and Public Health Lab, Department of Zoology, University of Lucknow, 226003, India
| | - Rakesh K. Gupta
- Department of Radiodiagnosis, SGPGIMS, Lucknow 226003, India
| | - Virendra Atam
- Department of Medicine, King George's Medical University, India
| | - Samir Mohindra
- Department of Gastroenterology, SGPGIMS, Lucknow, UP, India
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45
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Abstract
The extrahepatic manifestations of hepatitis C include effects on the central nervous system, which have been associated with the ability of hepatitis C virus (HCV) to replicate in microglial and endothelial cells and the chronic inflammation induced by HCV. HCV can induce impaired neurocognition, which is clinically manifested by impaired quality of life, fatigue, and brain fog. These cognitive defects can be present even in patients with mild histologic HCV and have been confirmed by neurocognitive testing and brain imaging by magnetic resonance spectroscopy. Neurocognitive defects include loss of functioning memory and subtle changes in attention and processing speed.
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Affiliation(s)
- Sentia Iriana
- Division of Gastroenterology & Hepatology, Beth Israel Deaconess Medical Center, 110 Francis Street, Boston, MA 02125, USA
| | - Michael P Curry
- Division of Gastroenterology & Hepatology, Beth Israel Deaconess Medical Center, 110 Francis Street, Boston, MA 02125, USA
| | - Nezam H Afdhal
- Division of Gastroenterology & Hepatology, Beth Israel Deaconess Medical Center, 110 Francis Street, Boston, MA 02125, USA.
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46
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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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47
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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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48
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Devlin KN, Giovannetti T. Heterogeneity of Neuropsychological Impairment in HIV Infection: Contributions from Mild Cognitive Impairment. Neuropsychol Rev 2017; 27:101-123. [PMID: 28536861 DOI: 10.1007/s11065-017-9348-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2016] [Accepted: 05/02/2017] [Indexed: 02/04/2023]
Abstract
Despite longstanding acknowledgement of the heterogeneity of HIV-associated neurocognitive disorders (HAND), existing HAND diagnostic methods classify according to the degree of impairment, without regard to the pattern of neuropsychological strengths and weaknesses. Research in mild cognitive impairment (MCI) has demonstrated that classifying individuals into subtypes by both their level and pattern of impairment, using either conventional or statistical methods, has etiologic and prognostic utility. Methods for characterizing the heterogeneity of MCI provide a framework that can be applied to other disorders and may be useful in clarifying some of the current challenges in the study of HAND. A small number of studies have applied these methods to examine the heterogeneity of neurocognitive function among individuals with HIV. Most have supported the existence of multiple subtypes of neurocognitive impairment, with some evidence for distinct clinicodemographic features of these subtypes, but a number of gaps exist. Following a review of diagnostic methods and challenges in the study of HAND, we summarize the literature regarding conventional and empirical subtypes of MCI and HAND and identify directions for future research regarding neurocognitive heterogeneity in HIV infection.
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Affiliation(s)
- Kathryn N Devlin
- Department of Psychology, Temple University, Weiss Hall, 1701 North 13th Street, Philadelphia, PA, 19122, USA.
| | - Tania Giovannetti
- Department of Psychology, Temple University, Weiss Hall, 1701 North 13th Street, Philadelphia, PA, 19122, USA
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49
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CX3CR1 + monocytes modulate learning and learning-dependent dendritic spine remodeling via TNF-α. Nat Med 2017; 23:714-722. [PMID: 28504723 PMCID: PMC5590232 DOI: 10.1038/nm.4340] [Citation(s) in RCA: 99] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2016] [Accepted: 04/11/2017] [Indexed: 02/07/2023]
Abstract
Impaired learning and cognitive function often occurs during systemic infection or inflammation. Although activation of the innate immune system has been linked to the behavioral and cognitive effects that are associated with infection, the underlying mechanisms remain poorly understood. Here we mimicked viral immune activation with poly(I:C), a synthetic analog of double-stranded RNA, and longitudinally imaged postsynaptic dendritic spines of layer V pyramidal neurons in the mouse primary motor cortex using two-photon microscopy. We found that peripheral immune activation caused dendritic spine loss, impairments in learning-dependent dendritic spine formation and deficits in multiple learning tasks in mice. These observed synaptic alterations in the cortex were mediated by peripheral-monocyte-derived cells and did not require microglial function in the central nervous system. Furthermore, activation of CX3CR1highLy6Clow monocytes impaired motor learning and learning-related dendritic spine plasticity through tumor necrosis factor (TNF)-α-dependent mechanisms. Taken together, our results highlight CX3CR1high monocytes and TNF-α as potential therapeutic targets for preventing infection-induced cognitive dysfunction.
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50
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Miller TR, Weiss JJ, Bräu N, Dieterich DT, Stivala A, Rivera-Mindt M. Greater decline in memory and global neurocognitive function in HIV/hepatitis C co-infected than in hepatitis C mono-infected patients treated with pegylated interferon and ribavirin. J Neurovirol 2017; 23:260-272. [PMID: 27896573 PMCID: PMC5334364 DOI: 10.1007/s13365-016-0494-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2016] [Revised: 09/21/2016] [Accepted: 10/20/2016] [Indexed: 12/18/2022]
Abstract
The human immunodeficiency virus (HIV), hepatitis C virus (HCV), and the treatment of HCV with pegylated interferon and ribavirin (IFN/RBV) have been associated with neurocognitive and psychiatric abnormalities. The goal of this research was to prospectively evaluate neurocognitive functioning among a group of HCV mono-infected and HIV/HCV co-infected patients during the first 24 weeks of IFN/RBV treatment while accounting for practice effects, normal variations in change over time, and variations in IFN/RBV treatment exposure. Forty-four HCV mono-infected and 30 HIV/HCV co-infected patients were enrolled in a prospective study of patients beginning on IFN/RBV for chronic HCV infection. Patients were administered a depression inventory, a measure of fatigue, a structured psychiatric interview, and a neurocognitive battery at baseline and 24 weeks after initiation of treatment. Analyses were conducted to explore possible associations between neurocognitive functioning and the following: HIV/HCV co-infection vs. HCV mono-infection, IFN and RBV treatment exposure, psychiatric status, liver disease stage, and other medical characteristics. At baseline, there were no significant differences between the two groups' neuropsychiatric or neurocognitive function other than the mono-infected group had significantly higher reports of fatigue (p = 0.033). Over the course of 24 weeks of treatment after controlling for practice effects, the HIV/HCV co-infected patients experienced significantly greater declines in memory (t(56) = 2.14, p = 0.037) and global neurocognitive functioning (t(53) = 2.28, p = 0.027). In a well-characterized sample of mono-infected and co-infected patients, it appears that persons with HIV/HCV co-infection are potentially more vulnerable to neurocognitive sequalae during HCV treatment.
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Affiliation(s)
- Theodore R Miller
- Department of Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, PO Box 1087, New York, NY, 10029, USA
- Yale School of Nursing, 400 West Campus Drive, Orange, CT, 06477, USA
| | - Jeffrey J Weiss
- Department of Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, PO Box 1087, New York, NY, 10029, USA.
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.
| | - Norbert Bräu
- Department of Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, PO Box 1087, New York, NY, 10029, USA
- Infectious Disease Section, Bronx Veterans Affairs Medical Center, 130 W. Kingsbridge Road, Bronx, New York, NY, 10468, USA
| | - Douglas T Dieterich
- Department of Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, PO Box 1087, New York, NY, 10029, USA
| | - Alicia Stivala
- Department of Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, PO Box 1087, New York, NY, 10029, USA
| | - Monica Rivera-Mindt
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA
- Psychology Department, Fordham University, DE 340, 441 E. Fordham Road, Bronx, NY, 10458, USA
- Department of Neurology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA
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