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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] [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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Narváez-Bandera I, Suárez-Gómez D, Castro-Rivera CDM, Camasta-Beníquez A, Durán-Quintana M, Cabrera-Ríos M, Isaza CE. Hepatitis C virus infection and Parkinson's disease: insights from a joint sex-stratified BioOptimatics meta-analysis. Sci Rep 2024; 14:22838. [PMID: 39354018 PMCID: PMC11445468 DOI: 10.1038/s41598-024-73535-0] [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: 02/19/2024] [Accepted: 09/18/2024] [Indexed: 10/03/2024] Open
Abstract
Hepatitis C virus (HCV) infection poses a significant public health challenge and often leads to long-term health complications and even death. Parkinson's disease (PD) is a progressive neurodegenerative disorder with a proposed viral etiology. HCV infection and PD have been previously suggested to be related. This work aimed to identify potential biomarkers and pathways that may play a role in the joint development of PD and HCV infection. Using BioOptimatics-bioinformatics driven by mathematical global optimization-, 22 publicly available microarray and RNAseq datasets for both diseases were analyzed, focusing on sex-specific differences. Our results revealed that 19 genes, including MT1H, MYOM2, and RPL18, exhibited significant changes in expression in both diseases. Pathway and network analyses stratified by sex indicated that these gene expression changes were enriched in processes related to immune response regulation in females and immune cell activation in males. These findings suggest a potential link between HCV infection and PD, highlighting the importance of further investigation into the underlying mechanisms and potential therapeutic targets involved.
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Affiliation(s)
- Isis Narváez-Bandera
- Bioengineering Graduate Program, The Applied Optimization Group, University of Puerto Rico-Mayagüez, Mayagüez, 00681, Puerto Rico
- Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, FL, 33612, USA
| | - Deiver Suárez-Gómez
- Bioengineering Graduate Program, The Applied Optimization Group, University of Puerto Rico-Mayagüez, Mayagüez, 00681, Puerto Rico
| | - Coral Del Mar Castro-Rivera
- Biology Department, The Applied Optimization Group, University of Puerto Rico-Mayagüez, Call Box 9000, Mayagüez, 00681, Puerto Rico
| | - Alaina Camasta-Beníquez
- Biology Department, The Applied Optimization Group, University of Puerto Rico-Mayagüez, Call Box 9000, Mayagüez, 00681, Puerto Rico
| | - Morelia Durán-Quintana
- Biology Department, The Applied Optimization Group, University of Puerto Rico-Mayagüez, Call Box 9000, Mayagüez, 00681, Puerto Rico
| | - Mauricio Cabrera-Ríos
- Bioengineering Graduate Program, The Applied Optimization Group, University of Puerto Rico-Mayagüez, Mayagüez, 00681, Puerto Rico
- Industrial Engineering Department, The Applied Optimization Group, University of Puerto Rico-Mayagüez, Mayagüez, 00681, Puerto Rico
| | - Clara E Isaza
- Bioengineering Graduate Program, The Applied Optimization Group, University of Puerto Rico-Mayagüez, Mayagüez, 00681, Puerto Rico.
- Biology Department, The Applied Optimization Group, University of Puerto Rico-Mayagüez, Call Box 9000, Mayagüez, 00681, Puerto Rico.
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Tayyaba M, Zahra SM, Naeem F, Sohail M. Family System and Gender as Predictors of Religious Coping in Pakistani Patients with Hepatitis C. JOURNAL OF RELIGION AND HEALTH 2024; 63:2466-2481. [PMID: 38085450 DOI: 10.1007/s10943-023-01970-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 11/21/2023] [Indexed: 05/02/2024]
Abstract
Pakistan has the second-largest number of HCV infections in the world with homogeneity across provinces and no evidence of decline over the past 30 years (Mahmud et al. in BMC Infect Dis 19(1):1-11, 2019). Currently, one in every 20 Pakistanis is suffering from HCV (Haqqi et al. in Viral Immunol 32(9):402-413, 2019). The disease significantly interferes with the everyday life of the patient (Silberbogen et al. in Psychosomatics 50(2):114-122, 2009; Foster in Viral Hepat 16(9):605-611, 2009). The present research aimed to find the role of gender, family system, and social support in predicting coping in patients with hepatitis C (HCV). A sample of 100 HCV patients was taken using purposive sampling from different public and private hospitals in Lahore, Pakistan. For assessment, the Multidimensional Scale of Perceived Social Support and Brief Cope Inventory were used. Results showed that male hepatitis C patients used a higher level of religious coping. Hepatitis C patients living in a joint family system used a higher level of religious coping. It also showed that there was no significant relationship between social support and coping. Patients suffering from hepatitis C for 2 years or more adopted avoidant coping strategies as compared to the patients diagnosed for 1 year or more. This research has important implications for psychologists, paramedical staff, doctors, social workers, caregivers, peers, and families of patients suffering from HCV. It would help in formulating effective therapeutic interventions. It would also add to the literature in the field of health psychology.
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Affiliation(s)
- Mubashra Tayyaba
- Department of Psychology, Lahore Garrison University, Sector C, DHA Phase 6, Lahore, Pakistan
| | - Syeda Mehreen Zahra
- Department of Psychology, Lahore Garrison University, Sector C, DHA Phase 6, Lahore, Pakistan
| | - Fatima Naeem
- Department of Psychology, Lahore Garrison University, Sector C, DHA Phase 6, Lahore, Pakistan
| | - Marva Sohail
- Department of Psychology, Lahore Garrison University, Sector C, DHA Phase 6, Lahore, Pakistan.
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Wang W, Pan D, Liu Q, Chen X, Wang S. L-Carnitine in the Treatment of Psychiatric and Neurological Manifestations: A Systematic Review. Nutrients 2024; 16:1232. [PMID: 38674921 PMCID: PMC11055039 DOI: 10.3390/nu16081232] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 04/13/2024] [Accepted: 04/19/2024] [Indexed: 04/28/2024] Open
Abstract
OBJECTIVE L-carnitine (LC), a vital nutritional supplement, plays a crucial role in myocardial health and exhibits significant cardioprotective effects. LC, being the principal constituent of clinical-grade supplements, finds extensive application in the recovery and treatment of diverse cardiovascular and cerebrovascular disorders. However, controversies persist regarding the utilization of LC in nervous system diseases, with varying effects observed across numerous mental and neurological disorders. This article primarily aims to gather and analyze database information to comprehensively summarize the therapeutic potential of LC in patients suffering from nervous system diseases while providing valuable references for further research. METHODS A comprehensive search was conducted in PubMed, Web Of Science, Embase, Ovid Medline, Cochrane Library and Clinicaltrials.gov databases. The literature pertaining to the impact of LC supplementation on neurological or psychiatric disorders in patients was reviewed up until November 2023. No language or temporal restrictions were imposed on the search. RESULTS A total of 1479 articles were retrieved, and after the removal of duplicates through both automated and manual exclusion processes, 962 articles remained. Subsequently, a meticulous re-screening led to the identification of 60 relevant articles. Among these, there were 12 publications focusing on hepatic encephalopathy (HE), while neurodegenerative diseases (NDs) and peripheral nervous system diseases (PNSDs) were represented by 9 and 6 articles, respectively. Additionally, stroke was addressed in five publications, whereas Raynaud's syndrome (RS) and cognitive disorder (CD) each had three dedicated studies. Furthermore, migraine, depression, and amyotrophic lateral sclerosis (ALS) each accounted for two publications. Lastly, one article was found for other symptoms under investigation. CONCLUSION In summary, LC has demonstrated favorable therapeutic effects in the management of HE, Alzheimer's disease (AD), carpal tunnel syndrome (CTS), CD, migraine, neurofibromatosis (NF), PNSDs, RS, and stroke. However, its efficacy appears to be relatively limited in conditions such as ALS, ataxia, attention deficit hyperactivity disorder (ADHD), depression, chronic fatigue syndrome (CFS), Down syndrome (DS), and sciatica.
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Affiliation(s)
- Wenbo Wang
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, and Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China; (W.W.); (D.P.); (X.C.)
| | - Da Pan
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, and Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China; (W.W.); (D.P.); (X.C.)
| | - Qi Liu
- Department of Public Health, School of Medicine, Xizang Minzu University, Xianyang 712082, China;
| | - Xiangjun Chen
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, and Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China; (W.W.); (D.P.); (X.C.)
- Department of Public Health, School of Medicine, Xizang Minzu University, Xianyang 712082, China;
| | - Shaokang Wang
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, and Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China; (W.W.); (D.P.); (X.C.)
- Department of Public Health, School of Medicine, Xizang Minzu University, Xianyang 712082, China;
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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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Selim R, Gordon SC, Zhou Y, Zhang T, Lu M, Daida YG, Boscarino JA, Schmidt MA, Trudeau S, Rupp LB, Gonzalez HC. Impact of hepatitis C treatment status on risk of Parkinson's disease and secondary parkinsonism in the era of direct-acting antivirals. J Viral Hepat 2023; 30:544-550. [PMID: 36872452 DOI: 10.1111/jvh.13826] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 02/10/2023] [Accepted: 02/28/2023] [Indexed: 03/07/2023]
Abstract
Research suggests a possible link between chronic infection with hepatitis C virus (HCV) and the development of Parkinson's Disease (PD) and secondary Parkinsonism (PKM). We investigated the impact of antiviral treatment status (untreated, interferon [IFN] treated, direct-acting antiviral [DAA] treated) and outcome (treatment failure [TF] or sustained virological response [SVR]) on risk of PD/PKM among patients with HCV. Using data from the Chronic Hepatitis Cohort Study (CHeCS), we applied a discrete time-to-event approach with PD/PKM as the outcome. We performed univariate followed by a multivariable modelling that used time-varying covariates, propensity scores to adjust for potential treatment selection bias and death as a competing risk. Among 17,199 confirmed HCV patients, we observed 54 incident cases of PD/PKM during a mean follow-up period of 17 years; 3753 patients died during follow-up. There was no significant association between treatment status/outcome and risk of PD/PKM. Type 2 diabetes tripled risk (hazard ratio [HR] 3.05; 95% CI 1.75-5.32; p < .0001) and presence of cirrhosis doubled risk of PD/PKM (HR 2.13, 95% CI 1.31-3.47). BMI >30 was associated with roughly 50% lower risk of PD/PKM than BMI <25 (HR 0.43; 0.22-0.84; p = .0138). After adjustment for treatment selection bias, we did not observe a significant association between HCV patients' antiviral treatment status/outcome on risk of PD/PKM. Several clinical risk factors-diabetes, cirrhosis and BMI-were associated with PD/PKM.
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Affiliation(s)
- Ranya Selim
- Department of Gastroenterology and Hepatology, Henry Ford Health, Detroit, Michigan, United States
| | - Stuart C Gordon
- Department of Gastroenterology and Hepatology, Henry Ford Health, Detroit, Michigan, United States.,School of Medicine, Wayne State University, Detroit, Michigan, United States
| | - Yueren Zhou
- Department of Public Health Sciences, Henry Ford Health, Detroit, Michigan, United States
| | - Talan Zhang
- Center on Aging & Health, Johns Hopkins University, Baltimore, Maryland, United States
| | - Mei Lu
- Center on Aging & Health, Johns Hopkins University, Baltimore, Maryland, United States
| | - Yihe G Daida
- Center for Integrated Health Care Research, Kaiser Permanente Hawaii, Honolulu, Hawaii, United States
| | | | - Mark A Schmidt
- Center for Health Research, Kaiser Permanente Northwest, Portland, Oregon, United States
| | - Sheri Trudeau
- Center on Aging & Health, Johns Hopkins University, Baltimore, Maryland, United States
| | - Loralee B Rupp
- Department of Health Policy and Health Systems Research, Henry Ford Health, Detroit, Michigan, United States
| | - Humberto C Gonzalez
- Department of Gastroenterology and Hepatology, Henry Ford Health, Detroit, Michigan, United States.,School of Medicine, Wayne State University, Detroit, Michigan, United States
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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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Buawangpong N, Pinyopornpanish K, Phinyo P, Jiraporncharoen W, Angkurawaranon C, Soontornpun A. Effect of Comorbidities on Ten-Year Survival in Patients with Dementia. J Alzheimers Dis 2023; 94:163-175. [PMID: 37212105 DOI: 10.3233/jad-221259] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/23/2023]
Abstract
BACKGROUND There is a verified association between comorbidity and survival in patients with dementia. OBJECTIVE To describe the ten-year survival probability of patients with dementia and to identify the impact of comorbidity. METHODS The prognostic retrospective cohort study was conducted using data from adults with dementia who had visited the outpatient departments at Maharaj Nakorn Chiang Mai hospital between 2006 and 2012. Dementia was verified in accordance with standard practice guidelines. Secondary data detailing about patient age, gender, date of dementia diagnosis and death, types of dementia, and comorbidities at the time of dementia diagnosis was obtained from electronic medical records. The association between comorbidity, patients' underlying disease at dementia diagnosis, and overall survival were analyzed using a multivariable Cox proportional hazard model adjusted for age, gender, types of dementia, and other comorbidities. RESULTS Of the 702 patients, 56.9% were female. Alzheimer's disease (39.6%) was the most prevalent type of dementia. Median overall survival was 6.0 years (95% CI 5.5- 6.7). The comorbidities associated with a high risk of mortality included liver disease (aHR 2.70, 95% CI 1.46- 5.00), atrial fibrillation (aHR 2.15, 95% CI 1.29- 3.58), myocardial infarction (aHR 1.55, 95% CI 1.07- 2.26), and type 2 diabetes mellitus (aHR 1.40, 95% CI 1.13- 1.74). CONCLUSION Overall survival rate of patients with dementia in Thailand was comparable to previous studies. Several comorbidities were associated with a ten-year survival. The prognosis of patients with dementia may be improved by appropriate care of comorbidities.
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Affiliation(s)
- Nida Buawangpong
- Department of Family Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
- Global Health and Chronic Conditions Research Group, Chiang Mai University, Chiang Mai, Thailand
| | - Kanokporn Pinyopornpanish
- Department of Family Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
- Global Health and Chronic Conditions Research Group, Chiang Mai University, Chiang Mai, Thailand
| | - Phichayut Phinyo
- Department of Family Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
- Center for Clinical Epidemiology and Clinical Statistics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
- Musculoskeletal Science and Translational Research (MSTR), Chiang Mai University, Chiang Mai, Thailand
| | - Wichuda Jiraporncharoen
- Department of Family Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
- Global Health and Chronic Conditions Research Group, Chiang Mai University, Chiang Mai, Thailand
| | - Chaisiri Angkurawaranon
- Department of Family Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
- Global Health and Chronic Conditions Research Group, Chiang Mai University, Chiang Mai, Thailand
| | - Atiwat Soontornpun
- Department of Internal Medicine, Division of Neurology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
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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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Montagnese S, Rautou PE, Romero-Gómez M, Larsen FS, Shawcross DL, Thabut D, Vilstrup H, Weissenborn K. EASL Clinical Practice Guidelines on the management of hepatic encephalopathy. J Hepatol 2022; 77:807-824. [PMID: 35724930 DOI: 10.1016/j.jhep.2022.06.001] [Citation(s) in RCA: 178] [Impact Index Per Article: 59.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Accepted: 06/01/2022] [Indexed: 12/12/2022]
Abstract
The EASL Clinical Practice Guidelines (CPGs) on the management of hepatic encephalopathy (HE) present evidence-based answers to a set of relevant questions (where possible, formulated in PICO [patient/population, intervention, comparison and outcomes] format) on the definition, diagnosis, differential diagnosis and treatment of HE. The document does not cover the pathophysiology of HE and does not cover all available treatment options. The methods through which it was developed and any information relevant to its interpretation are also provided.
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Gairing SJ, Schleicher EM, Labenz C. Diabetes mellitus - risk factor and potential future target for hepatic encephalopathy in patients with liver cirrhosis? Metab Brain Dis 2022; 38:1691-1700. [PMID: 36001211 DOI: 10.1007/s11011-022-01068-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Accepted: 08/08/2022] [Indexed: 10/15/2022]
Abstract
Hepatic encephalopathy (HE) is one of the major complications of cirrhosis, and its presence is associated with poor survival. Several risk factors for HE are well established, including age, history of HE, portosystemic shunts, or poorer liver function. In recent years, diabetes mellitus (DM) has emerged as another potential risk factor for the development of HE. This may be important for many patients, as the incidence of type 2 DM (T2DM) is increasing worldwide and, consequently, the incidence of NAFLD-related cirrhosis is rising simultaneously. In addition, DM is a critical factor in the progression of other liver diseases, such as alcohol-related liver disease. Thus, the number of patients with cirrhosis and comorbid T2DM will also increase. To date, the prevalence of DM already ranges between 22 - 40% in patients with cirrhosis. DM-associated factors that may influence the risk of HE include systemic inflammation, insulin resistance with increased muscle protein breakdown as well as autonomic dysfunction with prolonged intestinal transit time and small intestinal bacterial overgrowth. Currently, the evidence for an association between DM and both minimal and overt HE is weak and it seems likely that only poor glycemic control has an impact on HE risk. In addition, there are some early signs indicating that DM may impair the response of patients with HE to pharmacological therapies such as rifaximin. Thus, improvements in the management of glycemic control may be a candidate future target to reduce the risk of HE. In this concise review, we summarize the current evidence on the association between DM and HE and its potential future implications.
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Affiliation(s)
- Simon Johannes Gairing
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, 55131, Mainz, Germany
- Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg- University, Mainz, Germany
| | - Eva Maria Schleicher
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, 55131, Mainz, Germany
- Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg- University, Mainz, Germany
| | - Christian Labenz
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, 55131, Mainz, Germany.
- Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg- University, Mainz, Germany.
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12
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Ivan I, Irincu L, Diaconu Ş, Falup-Pecurariu C. Parkinsonism associated with viral infection. INTERNATIONAL REVIEW OF NEUROBIOLOGY 2022; 165:1-16. [PMID: 36208896 DOI: 10.1016/bs.irn.2022.07.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
There are several known causes of secondary parkinsonism, the most common being head trauma, stroke, medications, or infections. A growing body of evidence suggests that viral agents may trigger parkinsonian symptoms, but the exact pathological mechanisms are still unknown. In some cases, lesions or inflammatory processes in the basal ganglia or substantia nigra have been found to cause reversible or permanent impairment of the dopaminergic pathway, leading to the occurrence of extrapyramidal symptoms. This chapter reviews current data regarding the viral agents commonly associated with parkinsonism, such as Epstein Barr virus (EBV), hepatitis viruses, human immunodeficiency virus (HIV), herpes viruses, influenza virus, coxsackie virus, and Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). We present possible risk factors, proposed pathophysiology mechanisms, published case reports, common associations, and prognosis in order to offer a concise overview of the viral spectrum involved in parkinsonism.
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Affiliation(s)
| | | | - Ştefania Diaconu
- County Clinic Hospital, Brașov, Romania; Faculty of Medicine, Transilvania University, Brașov, Romania.
| | - Cristian Falup-Pecurariu
- County Clinic Hospital, Brașov, Romania; Faculty of Medicine, Transilvania University, Brașov, Romania
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13
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Brain temperature as an indicator of neuroinflammation induced by typhoid vaccine: Assessment using whole-brain magnetic resonance spectroscopy in a randomised crossover study. Neuroimage Clin 2022; 35:103053. [PMID: 35617872 PMCID: PMC9136180 DOI: 10.1016/j.nicl.2022.103053] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Revised: 05/16/2022] [Accepted: 05/17/2022] [Indexed: 11/23/2022]
Abstract
MRSI-derived whole-brain temperature did not detect low-level neuroinflammation. Regional brain temperature was a more sensitive measure of neuroinflammation. MRSI/EPSI might be a useful measure of neuroinflammation in psychiatric disorders. Prior studies indicate a pathogenic role of neuroinflammation in psychiatric disorders; however, there are no accepted methods that can reliably measure low-level neuroinflammation non-invasively in these individuals. Magnetic resonance spectroscopic imaging (MRSI) is a versatile, non-invasive neuroimaging technique that demonstrates sensitivity to brain inflammation. MRSI in conjunction with echo-planar spectroscopic imaging (EPSI) measures brain metabolites to derive whole-brain and regional brain temperatures, which may increase in neuroinflammation. The validity of MRSI/EPSI for measurement of low level neuroinflammation was tested using a safe experimental model of human brain inflammation – intramuscular administration of typhoid vaccine. Twenty healthy volunteers participated in a double-blind, placebo-controlled crossover study including MRSI/EPSI scans before and 3 h after vaccine/placebo administration. Body temperature and mood, assessed using the Profile of Mood States, were measured every hour up to four hours post-treatment administration. A mixed model analysis of variance was used to test for treatment effects. A significant proportion of brain regions (44/47) increased in temperature post-vaccine compared to post-placebo (p < 0.0001). For temperature change in the brain as a whole, there was no significant treatment effect. Significant associations were seen between mood scores assessed at 4 h and whole brain and regional temperatures post-treatment. Findings indicate that regional brain temperature may be a more sensitive measure of low-level neuroinflammation than whole-brain temperature. Future work where these measurement techniques are applied to populations with psychiatric disorders would be of clinical interest.
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Huang L, Wang Y, Tang Y, He Y, Han Z. Lack of Causal Relationships Between Chronic Hepatitis C Virus Infection and Alzheimer’s Disease. Front Genet 2022; 13:828827. [PMID: 35356425 PMCID: PMC8959984 DOI: 10.3389/fgene.2022.828827] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2021] [Accepted: 01/20/2022] [Indexed: 01/27/2023] Open
Affiliation(s)
- Lin Huang
- Department of Bioinformatics, School of Basic Medicine, Chongqing Medical University, Chongqing, China
| | - Yongheng Wang
- Department of Bioinformatics, School of Basic Medicine, Chongqing Medical University, Chongqing, China
- International Research Laboratory of Reproduction and Development, Chongqing Medical University, Chongqing, China
| | - Yaqin Tang
- Department of Bioinformatics, School of Basic Medicine, Chongqing Medical University, Chongqing, China
| | - Yijie He
- Department of Bioinformatics, School of Basic Medicine, Chongqing Medical University, Chongqing, China
| | - Zhijie Han
- Department of Bioinformatics, School of Basic Medicine, Chongqing Medical University, Chongqing, China
- *Correspondence: Zhijie Han,
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15
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Esmael A, Belal T, Amer IF, Samra E, Elmongui A, Shawki S. Predictive value of P300 event-related potential component in early cognitive impairment in patients with uncomplicated newly diagnosed hepatitis C virus. THE EGYPTIAN JOURNAL OF NEUROLOGY, PSYCHIATRY AND NEUROSURGERY 2022. [DOI: 10.1186/s41983-022-00450-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Cognitive impairment in patients with hepatitis C virus (HCV) is reported in the early onset of HCV infection without hepatic cirrhosis or marked liver impairment. Methods currently available to identify the risk for early cognitive impairment in hepatitis C virus (HCV) infection do not combine enough sensitivity and specificity. The present study aimed to evaluate the P 300 components of event-related potential (ERP) abnormalities as valid biomarkers for prediction and diagnosis of the cognitive impairment in newly diagnosed hepatitis C virus infection. This study is a case–control involved fifty patients newly diagnosed HCV and fifty age and sex-matched healthy controls. Assessments of cognitive functions were carried out by the Mini-mental State Examination, Wechsler Memory Scale Revised short form, and The Wechsler Adult Intelligence Scale, in addition to estimation of the amplitude and the latency of the P300 by the event-related potentials.
Results
Neuropsychological scales suggested the early incidence of cognitive impairment among hepatitis C virus patients. The electrophysiological study showed significant prolongation of P300 latency and decreased amplitude in HCV patients group compared with the control group. A binary logistic regression detected that P 300 latency ≥ 369 ms was significantly accompanied by a threefold increased risk of impaired cognition (OR 3.09, 95% CI 1.59–5.72, P < 0.01), while P 300 amplitude ≤ 8.2 μv was significantly accompanied by a twofold increased risk of impaired cognition (OR 2.18, 95% 1.43–4.05, P < 0.01).
Conclusion
This study concluded that the P300 event-related potentials components are valid biomarker as easy, noninvasive assessment and cost-effective method of early cognitive impairment in patients with uncomplicated newly diagnosed hepatitis C virus.
Registration of Clinical Trial Research
ClinicalTrials.gov ID: NCT04389268. https://clinicaltrials.gov/ct2/show/NCT04389268
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16
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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: 2] [Impact Index Per Article: 0.5] [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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A Review on Extrahepatic Manifestations of Chronic Hepatitis C Virus Infection and the Impact of Direct-Acting Antiviral Therapy. Viruses 2021; 13:v13112249. [PMID: 34835054 PMCID: PMC8619859 DOI: 10.3390/v13112249] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 11/02/2021] [Accepted: 11/05/2021] [Indexed: 02/06/2023] Open
Abstract
Extrahepatic manifestations are a feature of chronic hepatitis C virus (HCV) infection. In the course of chronic HCV infection, about 70% of patients have one or more extrahepatic manifestations. The latter are often the first and only clinical sign of infection. Experimental and clinical data support a causal association for many extrahepatic manifestations and HCV infection, which include mixed cryoglobulinemia, non-Hodgkin lymphomas (NHL), cardiovascular disease, insulin resistance, type 2 diabetes, neurological and psychiatric disease and other rheumatic diseases. All these extrahepatic conditions influence the morbidity, quality of life and mortality of HCV-infected patients. Currently, interferon-free therapeutic regimens with direct-acting antiviral agents (DAA) offer the possibility of treatment to almost the entire infected population, irrespective of stage of cirrhosis and associated serious comorbidities, always maintaining a high efficacy and tolerability. Several studies have shown a close association between HCV clearance by DAAs and an improvement or reduction in the risk of extrahepatic manifestations. Patients with HCV after a sustained virologic response (SVR) by DAA treatment have a lower risk than non-responders of developing cryoglobulinemic vasculitis and B-cell non-Hodgkin’s lymphomas. Furthermore, the SVR by DAA also reduces the risk of acute coronary syndrome, cardiovascular disease, insulin resistance and type 2 diabetes, and it improves atherosclerosis. HCV clearance by DAA also improves the quality of life and survival of patients with chronic HCV infection with associated extrahepatic diseases. Thus, DAAs should be initiated as early as possible in HCV patients with extrahepatic manifestations.
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18
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Naveed Z, Fox HS, Wichman CS, May P, Arcari CM, Meza J, Baccaglini L. An assessment of factors associated with neurocognitive decline in people living with HIV. Int J STD AIDS 2021; 33:38-47. [PMID: 34565257 DOI: 10.1177/09564624211043351] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Despite the widespread use of combination antiretroviral therapy (cART), HIV-associated neurocognitive impairment (NCI) remains a health concern. However, limited research has been done to identify factors associated with neurocognitive decline. We assessed risk factors associated with neurocognitive decline in people living with HIV using a definition of decline that is statistically easy to adopt, is based on a commonly used neuropsychological cut-off and may be clinically relevant. Cox proportional hazards modeling was performed using the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) study database. 581 participants were followed for up to 12 years. Neurocognitive decline was defined as the first observed drop in global T-scores of at least 2.67. Lifetime methamphetamine use had the strongest association with neurocognitive decline (adjusted Hazard Ratio; aHR = 1.48; 95% CI = 0.92-2.39) followed by no current antiretroviral medication use (aHR = 1.32; 95% CI = 0.91-1.92). Other risk factors included Hispanic ethnicity, lifetime history of major depressive disorder, lifetime cannabis use, hepatitis-C infection, and difficulty eating, dressing, bathing, or using the toilet. Results indicate that consistent use of ART may be of high significance to preserving neurocognition. Furthermore, Hispanic patients, those with a history of depression and substance use, and those having difficulty in essential activities of daily living may require vigilant follow-up.
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Affiliation(s)
- Zaeema Naveed
- Department of Epidemiology, 12284University of Nebraska Medical Center, Omaha, NE, USA
| | - Howard S Fox
- Department of Neurological Sciences, 12284University of Nebraska Medical Center, Omaha, NE, USA
| | - Christopher S Wichman
- Department of Biostatistics, 12284University of Nebraska Medical Center, Omaha, NE, USA
| | - Pamela May
- Department of Neurological Sciences, 12284University of Nebraska Medical Center, Omaha, NE, USA
| | - Christine M Arcari
- Department of Epidemiology, 12284University of Nebraska Medical Center, Omaha, NE, USA
| | - Jane Meza
- Department of Biostatistics, 12284University of Nebraska Medical Center, Omaha, NE, USA
| | - Lorena Baccaglini
- Department of Epidemiology, 12284University of Nebraska Medical Center, Omaha, NE, USA
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Faccioli J, Nardelli S, Gioia S, Riggio O, Ridola L. Neurological and psychiatric effects of hepatitis C virus infection. World J Gastroenterol 2021; 27:4846-4861. [PMID: 34447230 PMCID: PMC8371503 DOI: 10.3748/wjg.v27.i29.4846] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 05/07/2021] [Accepted: 06/04/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infection is widespread and affects 71 million people worldwide. Although hepatic manifestations are the most frequent, ranging from chronic hepatitis to cirrhosis and hepatocellular carcinoma, it is also associated with several extrahepatic manifestations. Infected patients may present non-specific neurological symptoms, regardless of the presence of liver cirrhosis. Several pathogenetic mechanisms underlying neurological symptoms have been hypothesized: neuroinvasion, immune-mediated damage, neurotransmitter alterations and cryoglobulinemia. Alterations of the central nervous system include cerebral vasculopathy, acute or subacute encephalopathy and inflammatory disorders. HCV infection may be responsible for neuropathies, of which the most frequent form is symmetrical axonal sensory or sensory-motor polyneuropathy which causes loss of leg sensitivity and weakness. Up to 50% of patients with HCV infection may experience cognitive decline and psychological disorders, such as depression and fatigue. HCV associated neurocognitive disorder is independent of the presence of liver cirrhosis and affects different domains than in patients with hepatic encephalopathy. It can be studied using specific tests that mainly explore executive functions, verbal learning and verbal recall. These disorders significantly reduce the quality of life. The new antiviral therapies improve the extrahepatic symptoms of HCV infection and their success depends on the achievement of sustained virological response. However, the effect of therapy may differ depending on the type of organ involved; neurological symptoms can be irreversible if there is organic liver damage. The aim of this review is to provide a critical overview of physiopathological mechanisms, diagnostic and therapeutic strategies of the neurological and psychiatric effects of HCV infection.
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Affiliation(s)
- Jessica Faccioli
- Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome 00185, Italy
| | - Silvia Nardelli
- Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome 00185, Italy
| | - Stefania Gioia
- Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome 00185, Italy
| | - Oliviero Riggio
- Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome 00185, Italy
| | - Lorenzo Ridola
- Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome 00185, Italy
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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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21
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Nevola R, Rinaldi L, Zeni L, Romano C, Marrone A, Galiero R, Pafundi PC, Acierno C, Vetrano E, Adinolfi LE. Changes in clinical scenarios, management, and perspectives of patients with chronic hepatitis C after viral clearance by direct-acting antivirals. Expert Rev Gastroenterol Hepatol 2021; 15:643-656. [PMID: 33445990 DOI: 10.1080/17474124.2021.1877136] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Hepatitis C virus (HCV) causes a systemic infection inducing hepatic and extrahepatic diseases. These latter involve cardiovascular system, kidney, brain, endocrine, glucose, and lipid metabolism, and the immune system. HCV infection is associated with an increased risk of morbidity and mortality for both hepatic and extrahepatic events. Direct-acting antivirals (DAA), introduced in the most recent years for HCV treatment, are effective in up to 99% of cases and have changed the clinical scenarios and management of these patients. AREAS COVERED The literature on the impact of HCV clearance by DAA on both hepatic and extrahepatic disease outcomes has been analyzed and discussed in this review in order to summarize the full therapeutic potential and its weaknesses. EXPERT OPINION Patients achieving HCV clearance have improved hepatic and extrahepatic diseases, quality of life and survival. They have lower incidence of cardiovascular disease, type 2 diabetes, kidney damage, and immuno-mediated manifestations. However, the improvements are related to the degree of pre-treatment organ damage. Therefore, a significant percentage of patients with advanced disease remains at risk of morbidity and mortality and must be monitored in the post-treatment. In addition, data emphasize the importance of starting treatment during the early stages of HCV infection.
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Affiliation(s)
- Riccardo Nevola
- Internal Medicine, Department of Advanced Medical and Surgery Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Luca Rinaldi
- Internal Medicine, Department of Advanced Medical and Surgery Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Letizia Zeni
- Internal Medicine, Department of Advanced Medical and Surgery Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Ciro Romano
- Internal Medicine, Department of Advanced Medical and Surgery Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Aldo Marrone
- Internal Medicine, Department of Advanced Medical and Surgery Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Raffaele Galiero
- Internal Medicine, Department of Advanced Medical and Surgery Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Pia Clara Pafundi
- Internal Medicine, Department of Advanced Medical and Surgery Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Carlo Acierno
- Internal Medicine, Department of Advanced Medical and Surgery Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Erica Vetrano
- Internal Medicine, Department of Advanced Medical and Surgery Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Luigi Elio Adinolfi
- Internal Medicine, Department of Advanced Medical and Surgery Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
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22
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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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Zahr NM, Pohl KM, Kwong AJ, Sullivan EV, Pfefferbaum A. Preliminary Evidence for a Relationship between Elevated Plasma TNFα and Smaller Subcortical White Matter Volume in HCV Infection Irrespective of HIV or AUD Comorbidity. Int J Mol Sci 2021; 22:ijms22094953. [PMID: 34067023 PMCID: PMC8124321 DOI: 10.3390/ijms22094953] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 04/27/2021] [Accepted: 04/28/2021] [Indexed: 02/08/2023] Open
Abstract
Classical inflammation in response to bacterial, parasitic, or viral infections such as HIV includes local recruitment of neutrophils and macrophages and the production of proinflammatory cytokines and chemokines. Proposed biomarkers of organ integrity in Alcohol Use Disorders (AUD) include elevations in peripheral plasma levels of proinflammatory proteins. In testing this proposal, previous work included a group of human immunodeficiency virus (HIV)-infected individuals as positive controls and identified elevations in the soluble proteins TNFα and IP10; these cytokines were only elevated in AUD individuals seropositive for hepatitis C infection (HCV). The current observational, cross-sectional study evaluated whether higher levels of these proinflammatory cytokines would be associated with compromised brain integrity. Soluble protein levels were quantified in 86 healthy controls, 132 individuals with AUD, 54 individuals seropositive for HIV, and 49 individuals with AUD and HIV. Among the patient groups, HCV was present in 24 of the individuals with AUD, 13 individuals with HIV, and 20 of the individuals in the comorbid AUD and HIV group. Soluble protein levels were correlated to regional brain volumes as quantified with structural magnetic resonance imaging (MRI). In addition to higher levels of TNFα and IP10 in the 2 HIV groups and the HCV-seropositive AUD group, this study identified lower levels of IL1β in the 3 patient groups relative to the control group. Only TNFα, however, showed a relationship with brain integrity: in HCV or HIV infection, higher peripheral levels of TNFα correlated with smaller subcortical white matter volume. These preliminary results highlight the privileged status of TNFα on brain integrity in the context of infection.
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Affiliation(s)
- Natalie M. Zahr
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA; (K.M.P.); (A.P.)
- Neuroscience Program, SRI International, Menlo Park, CA 94025, USA;
- Correspondence: ; Tel.: +1-650-859-5243
| | - Kilian M. Pohl
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA; (K.M.P.); (A.P.)
- Neuroscience Program, SRI International, Menlo Park, CA 94025, USA;
| | - Allison J. Kwong
- Gastroenterology and Hepatology Medicine, Stanford University School of Medicine, Stanford, CA 94350, USA;
| | | | - Adolf Pfefferbaum
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA; (K.M.P.); (A.P.)
- Neuroscience Program, SRI International, Menlo Park, CA 94025, USA;
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24
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Affiliation(s)
- Patrice Cacoub
- From the Department of Internal Medicine and Clinical Immunology, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Centre de Référence des Maladies Auto-Immunes Systémiques Rares and Centre de Référence des Maladies Auto-Inflammatoires et de l'Amylose Inflammatoire, Institut National de la Santé et de la Recherche Médicale UMR S 959, Centre National de la Recherche Scientifique FRE3632, and the Inflammation-Immunopathology-Biotherapy Department, Sorbonne Université - all in Paris
| | - David Saadoun
- From the Department of Internal Medicine and Clinical Immunology, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Centre de Référence des Maladies Auto-Immunes Systémiques Rares and Centre de Référence des Maladies Auto-Inflammatoires et de l'Amylose Inflammatoire, Institut National de la Santé et de la Recherche Médicale UMR S 959, Centre National de la Recherche Scientifique FRE3632, and the Inflammation-Immunopathology-Biotherapy Department, Sorbonne Université - all in Paris
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25
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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] [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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26
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Ostojic SM. Diagnostic and Pharmacological Potency of Creatine in Post-Viral Fatigue Syndrome. Nutrients 2021; 13:nu13020503. [PMID: 33557013 PMCID: PMC7913646 DOI: 10.3390/nu13020503] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 01/27/2021] [Accepted: 01/28/2021] [Indexed: 12/14/2022] Open
Abstract
Post-viral fatigue syndrome (PVFS) is a widespread chronic neurological disease with no definite etiological factor(s), no actual diagnostic test, and no approved pharmacological treatment, therapy, or cure. Among other features, PVFS could be accompanied by various irregularities in creatine metabolism, perturbing either tissue levels of creatine in the brain, the rates of phosphocreatine resynthesis in the skeletal muscle, or the concentrations of the enzyme creatine kinase in the blood. Furthermore, supplemental creatine and related guanidino compounds appear to impact both patient- and clinician-reported outcomes in syndromes and maladies with chronic fatigue. This paper critically overviews the most common disturbances in creatine metabolism in various PVFS populations, summarizes human trials on dietary creatine and creatine analogs in the syndrome, and discusses new frontiers and open questions for using creatine in a post-COVID-19 world.
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Affiliation(s)
- Sergej M. Ostojic
- FSPE Applied Bioenergetics Lab, University of Novi Sad, 21000 Novi Sad, Serbia;
- Faculty of Health Sciences, University of Pecs, H-7621 Pecs, Hungary
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27
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Smeyne RJ, Noyce AJ, Byrne M, Savica R, Marras C. Infection and Risk of Parkinson's Disease. JOURNAL OF PARKINSONS DISEASE 2021; 11:31-43. [PMID: 33361610 PMCID: PMC7990414 DOI: 10.3233/jpd-202279] [Citation(s) in RCA: 65] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Parkinson’s disease (PD) is thought to be caused by a combination of genetic and environmental factors. Bacterial or viral infection has been proposed as a potential risk factor, and there is supporting although not entirely consistent epidemiologic and basic science evidence to support its role. Encephalitis caused by influenza has included parkinsonian features. Epidemiological evidence is most compelling for an association between PD and hepatitis C virus. Infection with Helicobacter pylori may be associated not only with PD risk but also response to levodopa. Rapidly evolving knowledge regarding the role of the microbiome also suggests a role of resident bacteria in PD risk. Biological plausibility for the role for infectious agents is supported by the known neurotropic effects of specific viruses, particular vulnerability of the substantia nigra and even the promotion of aggregation of alpha-synuclein. A common feature of implicated viruses appears to be production of high levels of cytokines and chemokines that can cross the blood-brain barrier leading to microglial activation and inflammation and ultimately neuronal cell death. Based on multiple avenues of evidence it appears likely that specific bacterial and particularly viral infections may increase vulnerability to PD. The implications of this for PD prevention requires attention and may be most relevant once preventive treatments for at-risk populations are developed.
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Affiliation(s)
- Richard J Smeyne
- Department of Neuroscience, Vickie and Jack Farber Institute of Neuroscience, Thomas Jefferson University, Philadelphia, PA, USA
| | - Alastair J Noyce
- Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK.,Department of Clinical and Movement Neurosciences, UCL Institute of Neurology, London, UK
| | - Matthew Byrne
- Department of Neuroscience, Vickie and Jack Farber Institute of Neuroscience, Thomas Jefferson University, Philadelphia, PA, USA
| | - Rodolfo Savica
- Department of Neurology, Mayo Clinic, Rochester, Minnesota and Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
| | - Connie Marras
- The Edmond J Safra Program in Parkinson's disease, Toronto Western Hospital and the University of Toronto, Toronto, Canada
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28
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Tsai PC, Chen CY, Kuo HT, Hung CH, Tseng KC, Lai HC, Peng CY, Wang JH, Chen JJ, Lee PL, Chien RN, Yang CC, Lo GH, Kao JH, Liu CJ, Liu CH, Yan SL, Bair MJ, Lin CY, Su WW, Chu CH, Chen CJ, Tung SY, Tai CM, Lin CW, Lo CC, Cheng PN, Chiu YC, Wang CC, Cheng JS, Tsai WL, Lin HC, Huang YH, Yeh ML, Huang CF, Hsieh MH, Huang JF, Dai CY, Chung WL, Ke CLK, Yu ML. Successful Antiviral Therapy Reduces Risk of Schizophrenia Among Chronic Hepatitis C Patients: A Nationwide Real-World Taiwanese Cohort (T-COACH). Open Forum Infect Dis 2020; 7:ofaa397. [PMID: 33376753 PMCID: PMC7751132 DOI: 10.1093/ofid/ofaa397] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Accepted: 08/27/2020] [Indexed: 01/12/2023] Open
Abstract
Background Chronic hepatitis C (CHC) has been associated with major psychoses, and interferon (IFN)-based therapy may cause psychiatric sequelae. We aimed to evaluate the effects of sustained virological response (SVR) on the incidence of major psychoses in a nationwide Taiwanese CHC cohort. Methods Fifteen thousand eight hundred thirty-six CHC Taiwanese who received IFN-based therapy were enrolled between 2003 and 2015. Of those, 12 723 patients were linked to the National Health Insurance Research Databases for the incidence of major psychoses. Death before major psychoses was considered a competing risk. Results Twenty-four patients developed new-onset major psychoses during 67 554 person-years (3.6 per 10 000 person-years), including 16 affective psychoses, 7 schizophrenia, and 1 organic psychotic condition. The incidence of major psychoses and affective psychoses did not differ between the SVR and non-SVR groups. The 10-year cumulative incidence of schizophrenia were significantly higher in the non-SVR than in SVR patients (0.14% vs 0.04%, P = .036). Cox subdistribution hazards showed that SVR and older age were associated with a significantly lower risk of schizophrenia (hazard ratio = 0.18 and 0.17). Sustained virological response was associated with decreased incidence of schizophrenia and majorly observed among patients with age <45 (P = .02). Conclusions Successful IFN-based therapy might reduce the incidence of schizophrenia among CHC patients, especially among younger patients.
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Affiliation(s)
- Pei-Chien Tsai
- Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital; Hepatitis Research Center, School of Medicine and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.,Health Management Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Chi-Yi Chen
- Department of Internal Medicine, Chiayi Christian Hospital, Chiayi, Taiwan
| | - Hsing-Tao Kuo
- Division of Hepatogastroenterology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Kuo-Chih Tseng
- Department of Gastroenterology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
| | - Hsueh-Chou Lai
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Cheng-Yuan Peng
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Jing-Houng Wang
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Jyh-Jou Chen
- Division of Gastroenterology and Hepatology, Chi-Mei Medical Center, Liouying, Tainan, Taiwan
| | - Pei-Lun Lee
- Division of Gastroenterology and Hepatology, Chi-Mei Medical Center, Liouying, Tainan, Taiwan
| | - Rong-Nan Chien
- Division of Hepatology, Department of Gastroenterology and Hepatology, Linkou Medical Center, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Chi-Chieh Yang
- Division of Gastroenterology, Department of Internal Medicine, Show Chwan Memorial Hospital, Changhua, Taiwan
| | - Gin-Ho Lo
- Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, National Taiwan University Hospital, Taipei, Taiwan
| | - Chen-Hua Liu
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, National Taiwan University Hospital, Taipei, Taiwan
| | - Sheng-Lei Yan
- Division of Gastroenterology, Department of Internal Medicine, Chang Bing Show-Chwan Memorial Hospital, Changhua, Taiwan
| | - Ming-Jong Bair
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan
| | - Chun-Yen Lin
- Division of Hepatology, Department of Gastroenterology and Hepatology, Linkou Medical Center, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Wei-Wen Su
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Cheng-Hsin Chu
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
| | - Chih-Jen Chen
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
| | - Shui-Yi Tung
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Chi-Ming Tai
- Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Chih-Wen Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Ching-Chu Lo
- Department of Internal Medicine, St. Martin De Porres Hospital - Daya, Chiayi, Taiwan
| | - Pin-Nan Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yen-Cheng Chiu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chia-Chi Wang
- Division of Gastroenterology, Department of Internal Medicine, Taipei Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, New Taipei, Taiwan
| | - Jin-Shiung Cheng
- Division of Gastroenterology and Hepatology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Wei-Lun Tsai
- Division of Gastroenterology and Hepatology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei, Veterans General Hospital, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei, Veterans General Hospital, Taipei, Taiwan.,Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital; Hepatitis Research Center, School of Medicine and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital; Hepatitis Research Center, School of Medicine and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Meng-Hsuan Hsieh
- Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital; Hepatitis Research Center, School of Medicine and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.,Health Management Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital; Hepatitis Research Center, School of Medicine and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital; Hepatitis Research Center, School of Medicine and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chung
- Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital; Hepatitis Research Center, School of Medicine and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chiao-Li Khale Ke
- Department of Psychiatry, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital; Hepatitis Research Center, School of Medicine and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
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Rose CF, Amodio P, Bajaj JS, Dhiman RK, Montagnese S, Taylor-Robinson SD, Vilstrup H, Jalan R. Hepatic encephalopathy: Novel insights into classification, pathophysiology and therapy. J Hepatol 2020; 73:1526-1547. [PMID: 33097308 DOI: 10.1016/j.jhep.2020.07.013] [Citation(s) in RCA: 244] [Impact Index Per Article: 48.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Revised: 07/01/2020] [Accepted: 07/03/2020] [Indexed: 02/07/2023]
Abstract
Hepatic encephalopathy (HE) is a frequent and serious complication of both chronic liver disease and acute liver failure. HE manifests as a wide spectrum of neuropsychiatric abnormalities, from subclinical changes (mild cognitive impairment) to marked disorientation, confusion and coma. The clinical and economic burden of HE is considerable, and it contributes greatly to impaired quality of life, morbidity and mortality. This review will critically discuss the latest classification of HE, as well as the pathogenesis and pathophysiological pathways underlying the neurological decline in patients with end-stage liver disease. In addition, management strategies, diagnostic approaches, currently available therapeutic options and novel treatment strategies are discussed.
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Affiliation(s)
- Christopher F Rose
- Hepato-Neuro Laboratory, CRCHUM, Université de Montréal, Montreal, Canada.
| | - Piero Amodio
- Department of Medicine, University of Padova, Padova, Italy
| | - Jasmohan S Bajaj
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - Radha Krishan Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | | | - Simon D Taylor-Robinson
- Department of Surgery and Cancer, St. Mary's Hospital Campus, Imperial College London, London, United Kingdom
| | - Hendrik Vilstrup
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Denmark
| | - Rajiv Jalan
- Liver Failure Group, Institute for Liver and Digestive Health, University College London, Royal Free Campus, London, United Kingdom; European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain.
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Intrinsic Brain Abnormalities in Patients with Hepatitis C Virus Infection with Cognitive Impairment: A Preliminary Resting-State fMRI Study. BIOMED RESEARCH INTERNATIONAL 2020; 2020:1693043. [PMID: 33204682 PMCID: PMC7655249 DOI: 10.1155/2020/1693043] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 10/22/2020] [Accepted: 10/24/2020] [Indexed: 11/17/2022]
Abstract
Purpose Patients with a hepatitis C virus (HCV) infection frequently exhibit various neuropsychiatric complications such as cognitive decline. This study is aimed at investigating alterations in regional and network-level neural function in patients with HCV infection and examining the association between these alterations and patients' cognition dysfunction. Methods The study included 17 patients with HCV infection and 17 healthy controls. These individuals had undergone resting-state functional magnetic resonance imaging as well as cognitive assessment using a battery of tests that were collectively called the "psychometric hepatic encephalopathy score (PHES)" examination. Analyses of amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity (FC) were conducted to assess, respectively, regional neural function and functional integration. Results HCV-infected patients performed significantly worse in cognitive tests. In the HCV group, ALFF decreased in Region 1 (left medial frontal gyrus and bilateral anterior cingulate gyrus) and Region 2 (right middle and superior frontal gyrus). The HCV group showed lower FC between Region 1 and right middle frontal gyrus, whereas they presented an increase in FC between Region 2 and the left supramarginal gyrus/superior temporal gyrus and right supramarginal gyrus. No significant correlation was observed between ALFF/FC measurements and PHES result. Conclusion This preliminary study presents additional evidence that HCV infection affects brain function, including local intrinsic neural activity and global functional integration.
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Fabrazzo M, Zampino R, Vitrone M, Sampogna G, Del Gaudio L, Nunziata D, Agnese S, Santagata A, Durante-Mangoni E, Fiorillo A. Effects of Direct-Acting Antiviral Agents on the Mental Health of Patients with Chronic Hepatitis C: A Prospective Observational Study. Brain Sci 2020; 10:E483. [PMID: 32726940 PMCID: PMC7463817 DOI: 10.3390/brainsci10080483] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Revised: 07/04/2020] [Accepted: 07/24/2020] [Indexed: 02/06/2023] Open
Abstract
In chronic hepatitis C (CHC) patients, interferon-based treatments showed toxicity, limited efficacy, and psychiatric manifestations. Direct-acting antiviral (DAA) agents appeared safer, though it remains unclear if they may exacerbate or foster mood symptoms in drug-naïve CHC patients. We evaluated 62 CHC patients' mental status, before and 12 weeks after DAA therapy, by assessment scales and psychometric instruments. We subdivided patients into two groups, CHC patients with (Group A) or without (Group B) a current and/or past psychiatric history. After DAA treatment, Group A patients showed low anxiety and improved depression, no variation in self-report distress, but worse general health perceptions. No significant difference emerged from coping strategies. Depression and anxiety improved in Group B, and no change emerged from total self-reported distress, except for somatization. Moreover, Group B increased problem-focused strategies for suppression of competing activities, and decreased strategies of instrumental social support. Contrarily, Group B reduced significantly emotion-focused strategies, such as acceptance and mental disengagement, and improved vitality, physical and social role functioning. DAA therapy is safe and free of hepatological and psychiatric side effects in CHC patients, regardless of current and/or past psychiatric history. In particular, patients without a psychiatric history also remarkably improved their quality of life.
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Affiliation(s)
- Michele Fabrazzo
- Department of Psychiatry, University of Campania “Luigi Vanvitelli”, Largo Madonna delle Grazie 1, 80138 Naples, Italy; (G.S.); (L.D.G.); (D.N.); (S.A.); (A.F.)
| | - Rosa Zampino
- Division of Internal Medicine, Unit of Infectious and Transplant Medicine, University of Campania “L. Vanvitelli”, AORN Ospedali dei Colli, Monaldi Hospital, Piazzale Ettore Ruggieri, 80131 Naples, Italy; (R.Z.); (M.V.); (A.S.); (E.D.-M.)
- Internal Medicine, Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Piazza Miraglia 1, 80138 Naples, Italy
| | - Martina Vitrone
- Division of Internal Medicine, Unit of Infectious and Transplant Medicine, University of Campania “L. Vanvitelli”, AORN Ospedali dei Colli, Monaldi Hospital, Piazzale Ettore Ruggieri, 80131 Naples, Italy; (R.Z.); (M.V.); (A.S.); (E.D.-M.)
| | - Gaia Sampogna
- Department of Psychiatry, University of Campania “Luigi Vanvitelli”, Largo Madonna delle Grazie 1, 80138 Naples, Italy; (G.S.); (L.D.G.); (D.N.); (S.A.); (A.F.)
| | - Lucia Del Gaudio
- Department of Psychiatry, University of Campania “Luigi Vanvitelli”, Largo Madonna delle Grazie 1, 80138 Naples, Italy; (G.S.); (L.D.G.); (D.N.); (S.A.); (A.F.)
| | - Daniela Nunziata
- Department of Psychiatry, University of Campania “Luigi Vanvitelli”, Largo Madonna delle Grazie 1, 80138 Naples, Italy; (G.S.); (L.D.G.); (D.N.); (S.A.); (A.F.)
| | - Salvatore Agnese
- Department of Psychiatry, University of Campania “Luigi Vanvitelli”, Largo Madonna delle Grazie 1, 80138 Naples, Italy; (G.S.); (L.D.G.); (D.N.); (S.A.); (A.F.)
| | - Anna Santagata
- Division of Internal Medicine, Unit of Infectious and Transplant Medicine, University of Campania “L. Vanvitelli”, AORN Ospedali dei Colli, Monaldi Hospital, Piazzale Ettore Ruggieri, 80131 Naples, Italy; (R.Z.); (M.V.); (A.S.); (E.D.-M.)
| | - Emanuele Durante-Mangoni
- Division of Internal Medicine, Unit of Infectious and Transplant Medicine, University of Campania “L. Vanvitelli”, AORN Ospedali dei Colli, Monaldi Hospital, Piazzale Ettore Ruggieri, 80131 Naples, Italy; (R.Z.); (M.V.); (A.S.); (E.D.-M.)
| | - Andrea Fiorillo
- Department of Psychiatry, University of Campania “Luigi Vanvitelli”, Largo Madonna delle Grazie 1, 80138 Naples, Italy; (G.S.); (L.D.G.); (D.N.); (S.A.); (A.F.)
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Abstract
Hepatits C virus (HCV) infection has been largely associated with extrahepatic comorbidities such as diseases related to dysregulation of the immune system, neuropsychiatric disorders, and cardiometabolic alterations. These clinical consequences, together with experimental evidence, suggest a potential (in)direct effect of HCV, contributing to the pathogenesis of these diseases. Various studies have reported a positive effect of viral eradication on occurrence and outcomes of extrahepatic diseases. These observations and the availability of safe and effective direct antiviral agents further underline the need to search for virological eradication in all infected individuals independent of the severity of the liver disease.
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Affiliation(s)
- Salvatore Petta
- Sezione di Gastroenterologia e Epatologia, PROMISE, Università di Palermo, Italia.
| | - Antonio Craxì
- Sezione di Gastroenterologia e Epatologia, PROMISE, Università di Palermo, Italia
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Neuroimaging Findings in Chronic Hepatitis C Virus Infection: Correlation with Neurocognitive and Neuropsychiatric Manifestations. Int J Mol Sci 2020; 21:ijms21072478. [PMID: 32252497 PMCID: PMC7177498 DOI: 10.3390/ijms21072478] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Revised: 03/26/2020] [Accepted: 03/31/2020] [Indexed: 01/18/2023] Open
Abstract
Chronic hepatitis C virus (HCV) infection is commonly associated with neurocognitive dysfunction, altered neuropsychological performance and neuropsychiatric symptoms. Quantifiable neuropsychological changes in sustained attention, working memory, executive function, verbal learning and recall are the hallmark of HCV-associated neurocognitive disorder (HCV-AND). This constellation is at variance with the neuropsychological complex that is seen in minimal hepatic encephalopathy, which is typified by an array of alterations in psychomotor speed, selective attention and visuo-constructive function. Noncognitive symptoms, including sleep disturbances, depression, anxiety and fatigue, which are less easily quantifiable, are frequently encountered and can dominate the clinical picture and the clinical course of patients with chronic HCV infection. More recently, an increased vulnerability to Parkinson’s disease among HCV-infected patients has also been reported. The degree to which neurocognitive and neuropsychiatric changes are due to HCV replication within brain tissues or HCV-triggered peripheral immune activation remain to be determined. Without absolute evidence that clearly exonerates or indicts HCV, our understanding of the so-called “HCV brain syndrome”, relies primarily on clinical and neuropsychological assessments, although other comorbidities and substance abuse may impact on neurocognitive function, thus confounding an appropriate recognition. In recent years, a number of functional and structural brain imaging studies have been of help in recognizing possible biological markers of HCV-AND, thus providing a rationale for guiding and justifying antiviral therapy in selected cases. Here, we review clinical, neuroradiological, and therapeutic responses to interferon-based and interferon-free regimens in HCV-related cognitive and neuropsychiatric disorder.
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Negro F. Natural History of Hepatic and Extrahepatic Hepatitis C Virus Diseases and Impact of Interferon-Free HCV Therapy. Cold Spring Harb Perspect Med 2020; 10:cshperspect.a036921. [PMID: 31636094 DOI: 10.1101/cshperspect.a036921] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The hepatitis C virus (HCV) infects 71.1 million persons and causes 400,000 deaths annually worldwide. HCV mostly infects the liver, causing acute and chronic necroinflammatory damage, which may progress toward cirrhosis and hepatocellular carcinoma. In addition, HCV has been associated with several extrahepatic manifestations. The advent of safe and effective direct-acting antivirals (DAAs) has made the dream of eliminating this public health scourge feasible in the medium term. Prospective studies using DAA-based regimens have shown the benefit of HCV clearance in terms of both liver- and non-liver-related mortality.
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Affiliation(s)
- Francesco Negro
- Divisions of Clinical Pathology and of Gastroenterology and Hepatology, University Hospital, 1211 Genève 4, Switzerland
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35
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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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Barokar J, McCutchan A, Deutsch R, Tang B, Cherner M, Bharti AR. Neurocognitive impairment is worse in HIV/HCV-coinfected individuals with liver dysfunction. J Neurovirol 2019; 25:792-799. [PMID: 31281947 PMCID: PMC6923581 DOI: 10.1007/s13365-019-00767-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Revised: 05/09/2019] [Accepted: 05/21/2019] [Indexed: 01/09/2023]
Abstract
Infections with HIV and hepatitis C virus (HCV) can individually and jointly contribute to neurocognitive impairment (NCI). Rates of NCI in HIV/HCV-coinfected persons range from 40 to 63% but its correlates have not been described. In this study, we examined HIV/HCV-coinfected adults on antiretroviral therapy (ART) with undetectable HIV RNA in blood (n = 412) who were assessed using a comprehensive neuropsychological test battery. Demographics, host and viral biomarkers, and markers of liver dysfunction were compared between impaired (n = 198) and unimpaired (n = 214) participants using logistic regression. The cohort was predominantly middle-aged men, half of whom (48%) had NCI. The odds of NCI increased by almost two-fold when serum albumin was < 4 g/dL, 1.7-fold when alanine aminotransferase (ALT) levels were > 50 IU/L, and 2.2-fold with every unit increase in log10 AST to Platelet Ratio Index (APRI). These readily available clinical biomarkers of NCI measure hepatic injury and/or dysfunction, suggesting a mechanism for the effects of HCV infection on NCI. They may identify patients at increased risk of NCI who could be prioritized for early initiation of HCV treatment to protect or improve cognition.
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Affiliation(s)
- Jyoti Barokar
- Department of Psychiatry, University of California, San Diego, USA
| | - Allen McCutchan
- Department of Medicine, University of California, San Diego, USA
| | - Reena Deutsch
- Department of Psychiatry, University of California, San Diego, USA
| | - Bin Tang
- Department of Psychiatry, University of California, San Diego, USA
| | - Mariana Cherner
- Department of Psychiatry, University of California, San Diego, USA
| | - Ajay R. Bharti
- Department of Medicine, University of California, San Diego, USA
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Barreira DP, Marinho RT, Bicho M, Flores I, Fialho R, Ouakinin S. Hepatitis C Pretreatment Profile and Gender Differences: Cognition and Disease Severity Effects. Front Psychol 2019; 10:2317. [PMID: 31681109 PMCID: PMC6804525 DOI: 10.3389/fpsyg.2019.02317] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Accepted: 09/27/2019] [Indexed: 12/12/2022] Open
Abstract
Background The hepatitis C virus (HCV) is known to infect the brain, however, the findings based on associated neuropsychiatric syndrome are controversial and the association itself remains unclear. Gender research in HCV infection is limited, failing to integrate the role of gender differences in neurocognitive syndrome. The aim of this study was to characterize psychological and neurocognitive profiles in HCV-infected patients before treatment and to explore gender differences in those profiles, as well as the impact of disease severity. Methods A total of 86 patients diagnosed with chronic hepatitis C were included. Depression and anxiety were assessed using Hamilton anxiety scale (HAM-A), Hamilton depression scale (HAM-D), Beck Depression Inventory (BDI). For cognition, a neuropsychological battery to measure attention, concentration and memory was used, and executive function components validated for the Portuguese population was also used before starting treatment. To identify the disease severity, platelet ratio index, and FibroScan® were used. Results A statistically significant gender effect was found on HAM-A (B = 0.64, CI: 0.17–1.11) and HAM-D (B = 0.62, CI: 0.14–1.09), with women scoring higher compared to men. Regarding neuropsychological scores, significant differences between gender were identified in executive functions measured by Trail Making Test (TMT B) (B = 0.48, CI: 0.02–0.97), TMT B-A (B = 0.26, CI: −39.2 to −3.7) and in digit span total (B = −0.52, CI: −1.0 to −0.04), with women performing worse than men. Controlling for years of substance dependence, TMT-B and TMT B-A showed significant gender differences. Regarding the presence or absence of substance dependence, only HAM-A and HAM-D remained significant. For categorical variables, Digit Span Total was also influenced by gender, with women being more likely to be impaired: odds ratio (OR) = 7.07, CI: 2.04–24.45), and a trend was observed for Digit Span Backward (OR = 3.57, CI: 1.31–9.75). No significant differences were found between disease severity and neurocognitive performance. Conclusion Data suggest that gender has an influence on depression, anxiety and cognitive functions with women showing greater impairment compared with men. This effect seems to be influenced by substance dependence.
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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
| | - 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
| | - Isabel Flores
- ISCTE, IUL, Centro de Investigação em Estudos Sociais, Lisbon, Portugal
| | - Renata Fialho
- Immunopsychiatric Clinic, Research and Development, Sussex Partnership NHS Foundation Trust, Brighton and Hove, United Kingdom
| | - Sílvia Ouakinin
- Clínica Universitária de Psiquiatria e Psicologia Médica, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
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Hassaan SH, Darwish AM, Khalifa H, Ramadan HKA, Hassany SM, Ahmed GK, Moustafa EF. Assessment of cognitive functions and psychiatric symptoms in hepatitis C patients receiving pegylated interferon alpha and ribavirin: A prospective cohort study. Int J Psychiatry Med 2019; 54:424-440. [PMID: 31219366 DOI: 10.1177/0091217419858277] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Objective This study aimed to prospectively evaluate cognitive functioning in hepatitis C virus patients before, during, and after interferon alpha and to assess the psychiatric side effects of interferon alpha such as depression and anxiety. Methods A total of 100 chronic hepatitis C virus patients eligible for interferon therapy from the hepatitis outpatient clinic of Assiut University Hospital were included. A full medical and psychiatric assessment was done using the Hamilton Depression Rating Scale (HAM-D) and Hamilton Anxiety Rating Scale (HAM-A). Cognitive assessment was done using The Mini-Mental State Examination (MMSE), Memory Assessment Scales (MAS), and Wechsler Adult Intelligence Scale (WAIS). Medical, cognitive, and psychiatric assessments were conducted at the start of the study and after starting the treatment at two, four, and six months. Results There was a significant increase in the mean scores of HAM-D (t = 7.739, p < 0.001; t = 5.707, p < 0.001; t = 5.115, p < 0.001) and HAM-A (t = 6.237, p < 0.001; t = 4.154, p < 0.001; t = 3.955, p < 0.001) scales at the two, four, and six month follow-ups, respectively, in comparison to the baseline measurements. As regards to the MAS, repeated assessments after two, four, and six months showed no statistically significant difference from the baseline apart from deterioration in the verbal memory performance after six months in comparison to the baseline (t = −2.605, p = 0.011). As regards to MMSE, the verbal intelligence quotient (IQ), performance IQ, and total IQ, there was a significant improvement in the patients’ cognitive performance, in comparison to the baseline, after two months (t = 2.144, p = 0.035), four months (t = 2.868, p = 0.002), and six months (t = 3.505, p = 0.001), respectively. There was also a significant negative correlation between HAM-D mean scores and the MAS verbal mean scores of the patients (r = −.219, p = 0.039). Conclusion There were increases in symptoms of depression and anxiety during interferon alpha and ribavirin treatment, which do not correlate with the patients’ cognitive performance. There was a significant improvement in cognitive performance except in verbal memory with the progress of interferon alpha treatment. Years of education, socioeconomic status, and lower quantitative polymerase chain reaction are predictors for better cognitive performance.
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Affiliation(s)
- Shehab H Hassaan
- Department of Neurology and Psychiatry, Assiut University, Egypt
| | - Alaa M Darwish
- Department of Neurology and Psychiatry, Assiut University, Egypt
| | - Hossam Khalifa
- Department of Neurology and Psychiatry, Assiut University, Egypt
| | | | - Sahar M Hassany
- Tropical Medicine and Gastroenterlogy, Assiut University, Egypt
| | - Gellan K Ahmed
- Department of Neurology and Psychiatry, Assiut University, Egypt
| | - Ehab F Moustafa
- Tropical Medicine and Gastroenterlogy, Assiut University, Egypt
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Loftis JM, Taylor J, Hudson R, Firsick EJ. Neuroinvasion and cognitive impairment in comorbid alcohol dependence and chronic viral infection: An initial investigation. J Neuroimmunol 2019; 335:577006. [PMID: 31325774 DOI: 10.1016/j.jneuroim.2019.577006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Revised: 07/03/2019] [Accepted: 07/09/2019] [Indexed: 12/16/2022]
Abstract
Viruses that invade the central nervous system (CNS) can cause neuropsychiatric impairments. Similarly, chronic alcohol exposure can induce inflammatory responses that alter brain function. However, the effects of a chronic viral infection and comorbid alcohol use on neuroinflammation and behavior are not well-defined. We investigated the role of heavy alcohol intake in regulating inflammatory responses and behavioral signs of cognitive impairments in mice infected with lymphocytic choriomeningitis virus (LCMV) clone 13. LCMV-infected mice exposed to alcohol had increased peripheral inflammation and impaired cognitive function (as indicated by performance on the novel object recognition test). Initial findings suggest that brain region-specific dysregulation of microglial response to viral infection may contribute to cognitive impairments in the context of heavy alcohol use.
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Affiliation(s)
- Jennifer M Loftis
- Research & Development Service, Veterans Affairs Portland Health Care System, Portland, OR, USA; Department of Psychiatry, Oregon Health & Science University, Portland, OR, USA; Methamphetamine Abuse Research Center, Veterans Affairs Portland Health Care System, Oregon Health & Science University, Portland, OR, USA.
| | - Jonathan Taylor
- Research & Development Service, Veterans Affairs Portland Health Care System, Portland, OR, USA; Department of Psychiatry, Oregon Health & Science University, Portland, OR, USA
| | - Rebekah Hudson
- Research & Development Service, Veterans Affairs Portland Health Care System, Portland, OR, USA; Department of Public Health and Preventive Medicine, Oregon Health & Science University, Portland, OR, USA
| | - Evan J Firsick
- Research & Development Service, Veterans Affairs Portland Health Care System, Portland, OR, USA
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40
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Ramirez-Zamora A, Hess CW, Nelson DR. Is Interferon Therapy for Hepatitis C Infection a Treatable Risk Factor for Parkinson Disease? JAMA Neurol 2019; 76:1006-1007. [PMID: 31168561 DOI: 10.1001/jamaneurol.2019.1377] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Affiliation(s)
- Adolfo Ramirez-Zamora
- Department of Neurology, Fixel Center for Neurological Diseases, University of Florida, Gainesville
| | - Christopher W Hess
- Department of Neurology, Fixel Center for Neurological Diseases, University of Florida, Gainesville
| | - David R Nelson
- Clinical and Translational Science Institute, Department of Medicine, University of Florida, Gainesville
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Talwar P, Gupta R, Kushwaha S, Agarwal R, Saso L, Kukreti S, Kukreti R. Viral Induced Oxidative and Inflammatory Response in Alzheimer's Disease Pathogenesis with Identification of Potential Drug Candidates: A Systematic Review using Systems Biology Approach. Curr Neuropharmacol 2019; 17:352-365. [PMID: 29676229 PMCID: PMC6482477 DOI: 10.2174/1570159x16666180419124508] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2017] [Revised: 03/19/2018] [Accepted: 04/10/2018] [Indexed: 02/07/2023] Open
Abstract
Alzheimer's disease (AD) is genetically complex with multifactorial etiology. Here, we aim to identify the potential viral pathogens leading to aberrant inflammatory and oxidative stress response in AD along with potential drug candidates using systems biology approach. We retrieved protein interactions of amyloid precursor protein (APP) and tau protein (MAPT) from NCBI and genes for oxidative stress from NetAge, for inflammation from NetAge and InnateDB databases. Genes implicated in aging were retrieved from GenAge database and two GEO expression datasets. These genes were individually used to create protein-protein interaction network using STRING database (score≥0.7). The interactions of candidate genes with known viruses were mapped using virhostnet v2.0 database. Drug molecules targeting candidate genes were retrieved using the Drug- Gene Interaction Database (DGIdb). Data mining resulted in 2095 APP, 116 MAPT, 214 oxidative stress, 1269 inflammatory genes. After STRING PPIN analysis, 404 APP, 109 MAPT, 204 oxidative stress and 1014 inflammation related high confidence proteins were identified. The overlap among all datasets yielded eight common markers (AKT1, GSK3B, APP, APOE, EGFR, PIN1, CASP8 and SNCA). These genes showed association with hepatitis C virus (HCV), Epstein- Barr virus (EBV), human herpes virus 8 and Human papillomavirus (HPV). Further, screening of drugs targeting candidate genes, and possessing anti-inflammatory property, antiviral activity along with a suggested role in AD pathophysiology yielded 12 potential drug candidates. Our study demonstrated the role of viral etiology in AD pathogenesis by elucidating interaction of oxidative stress and inflammation causing candidate genes with common viruses along with the identification of potential AD drug candidates.
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Affiliation(s)
- Puneet Talwar
- Genomics and Molecular Medicine Unit, Institute of Genomics and Integrative Biology (IGIB), Council of Scientific and Industrial Research (CSIR), Delhi, India
| | - Renu Gupta
- Institute of Human Behaviour & Allied Sciences (IHBAS), Dilshad Garden, Delhi 110 095, India
| | - Suman Kushwaha
- Institute of Human Behaviour & Allied Sciences (IHBAS), Dilshad Garden, Delhi 110 095, India
| | - Rachna Agarwal
- Institute of Human Behaviour & Allied Sciences (IHBAS), Dilshad Garden, Delhi 110 095, India
| | - Luciano Saso
- Department of Physiology and Pharmacology, Sapienza University of Rome, Italy
| | | | - Ritushree Kukreti
- Genomics and Molecular Medicine Unit, Institute of Genomics and Integrative Biology (IGIB), Council of Scientific and Industrial Research (CSIR), Delhi, India
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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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Bladowska J, Pawłowski T, Fleischer-Stępniewska K, Knysz B, Małyszczak K, Żelwetro A, Rymer W, Inglot M, Waliszewska-Prosół M, Ejma M, Podgórski P, Zimny A, Sąsiadek M. Interferon-free therapy as the cause of white matter tracts and cerebral perfusion recovery in patients with chronic hepatitis C. J Viral Hepat 2019; 26:635-643. [PMID: 30702208 DOI: 10.1111/jvh.13069] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Accepted: 01/09/2019] [Indexed: 02/06/2023]
Abstract
The purpose of this study was to assess cerebral microstructural and perfusion changes in patients with chronic hepatitis C virus (HCV) infection before and after interferon-free therapy, using advanced magnetic resonance (MR) techniques. Eleven HCV-positive patients underwent diffusion tensor imaging (DTI) and perfusion-weighted imaging (PWI) using a 1.5T MR unit, before and 24 weeks after completion of interferon-free therapy. DTI fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were obtained from 14 white matter tracts. PWI values of relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) were assessed from 8 areas, including basal ganglia, and cortical and white matter locations. In HCV-positive patients therapy with ombitasvir, paritaprevir boosted with ritonavir and dasabuvir, with or without ribavirin, was scheduled. Cognitive tests were used to assess cognitive function. We found increased FA values after interferon-free therapy compared to values obtained before treatment in HCV patients in almost all white matter tracts. We also observed elevated rCBV values in basal ganglia after therapy. There were significant correlations between improvement in the score of cognitive tests and increased FA values in both inferior fronto-occipital fascicles and left posterior cingulum after treatment. Liver fibrosis regression in elastography, APRI and improvement in cognitive tests were observed. This is the first report of interferon-free therapy as the cause of white matter tracts recovery as well as cerebral perfusion improvement in HCV-infected patients, indicating better functioning of frontal lobes after interferon-free treatment.
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Affiliation(s)
- Joanna Bladowska
- Department of General Radiology, Interventional Radiology and Neuroradiology, Wroclaw Medical University, Wroclaw, Poland
| | - Tomasz Pawłowski
- Division of Psychotherapy and Psychosomatic Medicine, Department of Psychiatry, Wroclaw Medical University, Wroclaw, Poland
| | - Katarzyna Fleischer-Stępniewska
- Department of Infectious Diseases, Liver Diseases and Acquired Immune Deficiency, Wroclaw Medical University, Wroclaw, Poland
| | - Brygida Knysz
- Department of Infectious Diseases, Liver Diseases and Acquired Immune Deficiency, Wroclaw Medical University, Wroclaw, Poland
| | - Krzysztof Małyszczak
- Division of Psychotherapy and Psychosomatic Medicine, Department of Psychiatry, Wroclaw Medical University, Wroclaw, Poland
| | | | - Weronika Rymer
- Department of Infectious Diseases, Liver Diseases and Acquired Immune Deficiency, Wroclaw Medical University, Wroclaw, Poland
| | - Małgorzata Inglot
- Department of Infectious Diseases, Liver Diseases and Acquired Immune Deficiency, Wroclaw Medical University, Wroclaw, Poland
| | | | - Maria Ejma
- Department of Neurology, Wroclaw Medical University, Wroclaw, Poland
| | - Przemysław Podgórski
- Department of General Radiology, Interventional Radiology and Neuroradiology, Wroclaw Medical University, Wroclaw, Poland
| | - Anna Zimny
- Department of General Radiology, Interventional Radiology and Neuroradiology, Wroclaw Medical University, Wroclaw, Poland
| | - Marek Sąsiadek
- Department of General Radiology, Interventional Radiology and Neuroradiology, Wroclaw Medical University, Wroclaw, Poland
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Dirks M, Haag K, Pflugrad H, Tryc AB, Schuppner R, Wedemeyer H, Potthoff A, Tillmann HL, Sandorski K, Worthmann H, Ding X, Weissenborn K. Neuropsychiatric symptoms in hepatitis C patients resemble those of patients with autoimmune liver disease but are different from those in hepatitis B patients. J Viral Hepat 2019; 26:422-431. [PMID: 30120896 DOI: 10.1111/jvh.12979] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2018] [Revised: 08/03/2018] [Accepted: 08/07/2018] [Indexed: 12/14/2022]
Abstract
Chronic fatigue, mood alterations and cognitive impairment are frequent accessory symptoms of HCV infection. Fatigue and mood alterations have also been observed in autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC), but not in hepatitis B virus (HBV)-infection, thus indicating an autoimmune response as possible cause of HCV infection-associated encephalopathy. Data, however, are sparse. This study aimed to prove that HCV patients feature similar to those with autoimmune liver disease but contrary to HBV patients regarding neuropsychiatric symptoms. A total of 132 noncirrhotic patients (HCV: 46, HBV: 22, AIH: 27, PBC: 29, AIH/PBC: 8) completed questionnaires addressing the domains mentioned above. Eighty-eight underwent a comprehensive neuropsychological assessment. Patient groups were compared among each other and to 33 healthy controls. Fatigue, anxiety and depression scores were significantly increased, and the SF-36 mental score significantly decreased in all patient groups compared to controls. Fatigue was significantly more pronounced in HCV than in HBV patients. HCV patients scored significantly worse than HBV patients but not AIH and PBC patients in the SF-36. HCV, AIH and PBC but not HBV patients did significantly worse than controls in word learning. Recognition of words was impaired in HCV, AIH and PBC patients and recognition of figures in HCV patients, exclusively (P ≤ 0.002). HCV patients did also worse than controls and HBV patients concerning alertness and working memory (P ≤ 0.001). The neuropsychiatric profiles of HCV patients are similar to those of AIH and PBC patients but differ from those of HBV patients, suggesting an autoimmune response as a possible cause for these differences.
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Affiliation(s)
- Meike Dirks
- Clinic for Neurology, Hannover Medical School, Hannover, Germany
| | - Kim Haag
- Clinic for Neurology, Hannover Medical School, Hannover, Germany
| | - Henning Pflugrad
- Clinic for Neurology, Hannover Medical School, Hannover, Germany
| | - Anita B Tryc
- Clinic for Neurology, Hannover Medical School, Hannover, Germany
| | - Ramona Schuppner
- Clinic for Neurology, Hannover Medical School, Hannover, Germany
| | - Heiner Wedemeyer
- Clinic for Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Andrej Potthoff
- Clinic for Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Hans L Tillmann
- Division of Gastroenterology, Hepatology & Nutrition, East Carolina University, Greenville, North Carolina
| | | | - Hans Worthmann
- Clinic for Neurology, Hannover Medical School, Hannover, Germany
| | - Xiaoqi Ding
- Institute for Diagnostic and Interventional Neuroradiology, Hannover Medical School, Hannover, Germany
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45
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Abo Hagar A, Ashour Y, Negm M, Abdelfatah M, Gad KA, Hashish E. Brain magnetic resonance spectroscopy and cognitive impairment in chronic hepatitis C patients. THE EGYPTIAN JOURNAL OF NEUROLOGY, PSYCHIATRY AND NEUROSURGERY 2018; 54:43. [PMID: 30613130 PMCID: PMC6302099 DOI: 10.1186/s41983-018-0046-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2018] [Accepted: 12/04/2018] [Indexed: 01/18/2023] Open
Abstract
Background Cognitive dysfunction in patients with chronic hepatitis C virus (HCV) infection may appear long before the development of severe liver cirrhosis. These alterations are not ascribed to hepatic encephalopathy; however, early detection is always difficult. Objective The aim of this study was to assess the changes of magnetic resonance spectroscopy (MRS) metabolites among chronic hepatitis C virus patients with and without cognitive impairment. Patients and methods A cross-sectional study was conducted in Suez Canal University Hospital. Forty-six HCV patients was included and divided into two groups: patients with and without cognitive impairment. Assessment of cognitive function was done using mini-mental state examination and Wechsler Memory Scale - Revised. Both groups were subjected to single-voxel MRS to evaluate metabolites in three brain regions: the basal ganglia, hippocampus, and posterior cingulate gyrus. Results The CHO/Cr was significantly higher, and NAA/Cr was significantly lower in group with cognitive impairment in the basal ganglia and posterior cingulate gyrus. Mini-mental state score had negative significant correlation with PCR of HCV. Mini-mental state score had significant negative and positive correlation with CHO/Cr and NAA/Cr, respectively, in the basal ganglia. All values of the Wechsler Memory Scale were statistically higher in the group without cognitive impairment except verbal memory score. Conclusion There were changes at brain metabolites associated with cognitive impairment in chronic hepatitis C patients regarding a decrease of NAA/Cr ratio and an increase of CHO/Cr ratio at the basal ganglia.
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Affiliation(s)
| | - Youssri Ashour
- Faculty of Medicine, Suez Canal University, Ismailia, Egypt
| | - Mohamed Negm
- Faculty of Medicine, Suez Canal University, Ismailia, Egypt
| | | | - Khaled A Gad
- Faculty of Medicine, Suez Canal University, Ismailia, Egypt
| | - Ehab Hashish
- Faculty of Medicine, Suez Canal University, Ismailia, Egypt
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46
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McCready H, Kohno M, Kolessar M, Dennis L, Kriz D, Luber H, Anderson R, Chang M, Sasaki A, Flora K, Vandenbark A, Mitchell SH, Loftis JM, Hoffman WF, Huckans M. Functional MRI and delay discounting in patients infected with hepatitis C. J Neurovirol 2018; 24:738-751. [PMID: 30298201 PMCID: PMC6279508 DOI: 10.1007/s13365-018-0670-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2017] [Revised: 04/23/2018] [Accepted: 08/15/2018] [Indexed: 02/06/2023]
Abstract
Hepatitis C virus-infected (HCV+) adults evidence increased rates of psychiatric and cognitive difficulties. This is the first study to use functional magnetic resonance imaging (fMRI) to examine brain activation in untreated HCV+ adults. To determine whether, relative to non-infected controls (CTLs), HCV+ adults exhibit differences in brain activation during a delay discounting task (DDT), a measure of one's tendency to choose smaller immediate rewards over larger delayed rewards-one aspect of impulsivity. Twenty adults with HCV and 26 CTLs completed an fMRI protocol during the DDT. Mixed effects regression analyses of hard versus easy trials of the DDT showed that, compared with CTLs, the HCV+ group exhibited less activation in the left lateral occipital gyrus, precuneus, and superior frontal gyrus. There were also significant interactive effects for hard-easy contrasts in the bilateral medial frontal gyrus, left insula, left precuneus, left inferior parietal lobule, and right temporal occipital gyrus; the CTL group evidenced a positive relationship between impulsivity and activation, while the HCV+ group exhibited a negative relationship. Within the HCV+ group, those with high viral load chose immediate rewards more often than those with low viral load, regardless of choice difficulty; those with low viral load chose immediate rewards more often on hard choices relative to easy choices. Results show that HCV+ patients exhibit greater impulsive behavior when presented with difficult choices, and impulsivity is negatively related to activation in regions important for cognitive control. Thus, interventions that decrease impulsive choice may be warranted with some HCV+ patients.
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Affiliation(s)
- Holly McCready
- Research and Development, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA
- Department of Behavioral Neuroscience, School of Medicine, Oregon Health and Science University, Portland, OR, USA
- Department of Psychiatry, School of Medicine, Oregon Health and Science University, Portland, OR, USA
| | - Milky Kohno
- Research and Development, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA
- Department of Behavioral Neuroscience, School of Medicine, Oregon Health and Science University, Portland, OR, USA
- Department of Psychiatry, School of Medicine, Oregon Health and Science University, Portland, OR, USA
| | - Michael Kolessar
- Research and Development, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA
- Department of PM&R and Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Laura Dennis
- Research and Development, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA
- Department of Behavioral Neuroscience, School of Medicine, Oregon Health and Science University, Portland, OR, USA
- Department of Psychiatry, School of Medicine, Oregon Health and Science University, Portland, OR, USA
| | - Daniel Kriz
- Research and Development, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA
| | - Hannah Luber
- Research and Development, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA
| | - Renee Anderson
- Research and Development, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA
| | - Michael Chang
- Research and Development, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA
- The Northwest Hepatitis C Resource Center, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA
| | - Anna Sasaki
- Research and Development, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA
- The Northwest Hepatitis C Resource Center, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA
| | - Kenneth Flora
- Department of Gastroenterology, The Oregon Clinic, Portland, OR, USA
| | - Arthur Vandenbark
- Research and Development, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA
- Department of Neurology, School of Medicine, Oregon Health and Science University, Portland, OR, USA
- Department of Molecular Microbiology and Immunology, School of Medicine, Oregon Health and Science University, Portland, OR, USA
| | - Suzanne H Mitchell
- Department of Behavioral Neuroscience, School of Medicine, Oregon Health and Science University, Portland, OR, USA
- Department of Psychiatry, School of Medicine, Oregon Health and Science University, Portland, OR, USA
- Oregon Institute of Occupational Health Sciences, School of Medicine, Oregon Health and Science University, Portland, OR, USA
| | - Jennifer M Loftis
- Research and Development, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA
- Department of Psychiatry, School of Medicine, Oregon Health and Science University, Portland, OR, USA
- The Northwest Hepatitis C Resource Center, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA
| | - William F Hoffman
- Research and Development, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA
- Department of Behavioral Neuroscience, School of Medicine, Oregon Health and Science University, Portland, OR, USA
- Department of Psychiatry, School of Medicine, Oregon Health and Science University, Portland, OR, USA
- Behavioral Health & Clinical Neurosciences Division, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA
| | - Marilyn Huckans
- Research and Development, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA.
- Department of Psychiatry, School of Medicine, Oregon Health and Science University, Portland, OR, USA.
- The Northwest Hepatitis C Resource Center, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA.
- Behavioral Health & Clinical Neurosciences Division, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA.
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47
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Fath-Elbab HK, Ahmed E, Mansour DF, Soliman WT. Event-related evoked potential versus clinical tests in assessment of subclinical cognitive impairment in chronic hepatitis C virus. THE EGYPTIAN JOURNAL OF NEUROLOGY, PSYCHIATRY AND NEUROSURGERY 2018; 54:35. [PMID: 30532514 PMCID: PMC6245136 DOI: 10.1186/s41983-018-0034-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2017] [Accepted: 10/19/2018] [Indexed: 01/01/2023] Open
Abstract
Context Chronic infection by hepatitis C virus causes impairment in neurocognitive function in up to 50% of patients which may not be detected by clinical tests. Aim Early detection of neurocognitive impairment in chronic hepatitis C patients and investigating the cognitive function in HCV patient by p300 and clinical test. Materials and methods The study included 60 patients with chronic hepatitis C and 30 healthy controls. Participants were subjected to a biochemical, hematological assessment, mini-mental state examination, Montreal Cognitive Assessment, P300, polymerase chain reaction (PCR), and fibroscan made for hepatitis C patients. Results The digit span, attention, concentration, and memory were significantly lower in patients than controls. The delayed P300 peak latency and the reduction of its amplitude were significantly evident in patients with liver fibrosis than the controls and patients without fibrosis. These abnormalities were significantly higher with increasing the grade of fibrosis. All patients with cognitive impairment (reduced mini-mental state score) had abnormal P300-evoked responses. P300 could detect neurocognitive impairment in some patients with normal neurocognitive functions by clinical test. P300 had sensitivity (100%), specificity (59.26), positive predictive value (75%), negative predictive value (100%), and accuracy (81.67) in the detection of neurocognitive impairment in HCV patient. Conclusion Patients with chronic hepatitis C infection had significant impairment in their cognitive functions. This impairment increases with the increase in grade of hepatic fibrosis. P300 can detect minimal and subclinical impairment of cognitive function at early stages of chronic hepatitis with accuracy (81.67). Trial registration PACTR on 19 march 2018 retrospectively. Identification number for the registry is PACTR201804003215168.
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Affiliation(s)
| | - Elham Ahmed
- Minia University Faculty of Medicine, Minia, Egypt
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48
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Mechanisms of neuropathogenesis in HIV and HCV: similarities, differences, and unknowns. J Neurovirol 2018; 24:670-678. [PMID: 30291565 DOI: 10.1007/s13365-018-0678-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2018] [Revised: 08/20/2018] [Accepted: 09/07/2018] [Indexed: 12/17/2022]
Abstract
HIV and hepatitis C virus (HCV) have both been associated with cognitive impairment. Combination antiretroviral therapy (cART) has dramatically changed the nature of cognitive impairment in HIV-infected persons, while the role of direct-acting antivirals (DAA) in neurocognition of HCV-infected individuals remains unclear. Also, whether HIV and HCV interact to promote neurocognitive decline or whether they each contribute an individual effect continues to be an open question. In this work, we review the virally mediated mechanisms of HIV- and HCV-mediated neuropathogenesis, with an emphasis on the role of dual infection, and discuss observed changes with HIV viral suppression and HCV functional cure on neurocognitive impairments.
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49
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Loftis JM, Valerio J, Taylor J, Huang E, Hudson R, Taylor-Young P, Chang M, Ho SB, Dieperink E, Miranda JL, Hauser P. S100B and Inflammatory Cytokine Levels in Blood as Potential Markers of Blood-Brain Barrier Damage and Psychiatric Impairment in Comorbid Hepatitis C Viral Infection and Alcohol Use Disorder. Alcohol Clin Exp Res 2018; 42:10.1111/acer.13796. [PMID: 29953169 PMCID: PMC6310679 DOI: 10.1111/acer.13796] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2017] [Accepted: 05/15/2018] [Indexed: 12/24/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection and alcohol use disorder (AUD) both adversely affect the immune system resulting in alterations in immune cell signaling and inflammatory processes. The aim of this study was to investigate how comorbid AUD contributes to abnormalities in inflammatory mediators and psychiatric impairments in adults with HCV. METHODS Alcohol use, mood, and inflammatory factors were evaluated at 3 time points (baseline, week 4, and week 12) in Veterans with HCV, with (n = 42) and without (n = 13) comorbid AUD. Peripheral indices of immune activation, blood-brain barrier (BBB) damage (S100 calcium-binding protein B [S100B]), liver function, and viral load were measured using immunoassays and polymerase chain reaction assays. RESULTS Comorbid AUD was associated with increased symptoms of depression and anxiety, elevated levels of liver enzymes, and altered expression of inflammatory factors. Alcohol consumption was positively correlated with the severity of psychiatric symptoms. Univariate analysis identified significant group differences in interleukin (IL)-8 (p = 0.006), IL-10 (p = 0.03), and S100B (p = 0.048), with increased levels in participants with AUD, which persisted over time despite reductions in alcohol use and no significant change in HCV viral load. Statistically significant effects of study group or time were not found for the other immune factors assessed. Exploratory receiver operating characteristic curve analysis evaluated the ability of IL-8, IL-10, and S100B to differentiate between levels of alcohol consumption and generated biomarker cutoff values used to identify low risk and unhealthy alcohol use groups. CONCLUSIONS These results demonstrate that HCV and comorbid AUD are associated with greater psychiatric impairments, potentially resulting from increased inflammation, dysregulated cytokine expression, and compromised BBB function. Alcohol-induced BBB damage may increase the risk of neuropathological consequences within the context of chronic HCV infection.
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Affiliation(s)
- Jennifer M. Loftis
- Research & Development Service, VA Portland Health Care System, Portland, OR, USA
- Department of Psychiatry, Oregon Health & Science University, Portland, OR, USA
| | - Juno Valerio
- Research & Development Service, VA Portland Health Care System, Portland, OR, USA
| | - Jonathan Taylor
- Research & Development Service, VA Portland Health Care System, Portland, OR, USA
- Department of Psychiatry, Oregon Health & Science University, Portland, OR, USA
| | - Elaine Huang
- Research & Development Service, VA Portland Health Care System, Portland, OR, USA
- Department of Psychiatry, Oregon Health & Science University, Portland, OR, USA
| | - Rebekah Hudson
- Research & Development Service, VA Portland Health Care System, Portland, OR, USA
| | - Patricia Taylor-Young
- Nursing Research Department, VA Portland Health Care System, Portland, OR, USA
- School of Nursing, Oregon Health & Science University, Portland, OR, USA
| | - Michael Chang
- Gastroenterology, VA Portland Health Care System, Portland, OR, USA
- Internal Medicine, Oregon Health & Science University, Portland, OR, USA
| | - Samuel B. Ho
- VA San Diego Healthcare System, San Diego, CA, USA
- Department of Medicine, University of California San Diego, San Diego, CA, USA
| | - Eric Dieperink
- Minneapolis VA Healthcare System, Minneapolis, MN, USA
- Department of Psychiatry, University of Minnesota School of Medicine, Minneapolis, MN, USA
| | - Juan Luis Miranda
- VA Long Beach Health Care System, 5901 E 7th St, Long Beach, CA, USA
| | - Peter Hauser
- VA Long Beach Health Care System, 5901 E 7th St, Long Beach, CA, USA
- Department of Psychiatry and Human Behavior, University of California-Irvine, Irvine, CA, USA
- Department of Psychiatry, University of California San Diego, San Diego, CA, USA
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50
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Yeoh SW, Holmes ACN, Saling MM, Everall IP, Nicoll AJ. Depression, fatigue and neurocognitive deficits in chronic hepatitis C. Hepatol Int 2018; 12:294-304. [PMID: 29931590 DOI: 10.1007/s12072-018-9879-5] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2018] [Accepted: 06/05/2018] [Indexed: 12/11/2022]
Abstract
Patients with chronic hepatitis C virus (HCV) infection experience a range of symptoms including depression, fatigue and neurocognitive deficits, impairing quality of life. Depression, in particular, may be reactive to increased psychosocial stress, and the physical symptoms of advanced HCV or associated comorbidities. However, even patients at an early stage of HCV infection, with minimal hepatic inflammation or comorbidities, report more depressive symptoms and fatigue than the general population. Similarly, specific neurocognitive deficits occur in early stage HCV infection and are independent of the presence of depression or encephalopathy. Therefore, intracerebral neurobiological changes associated with HCV may potentially explain these symptoms. These changes may arise from infiltration of the brain by peripherally induced cytokines, as well as direct neuropathic effects of HCV viral particles penetrating the blood-brain barrier. These phenomena parallel those reported in human immunodeficiency virus (HIV) infection. HCV-associated intracerebral changes include upregulated inflammatory responses, altered neurotransmitter levels, hormonal dysregulation, and release of neurotoxic substances. These may subsequently lead to abnormal neuronal conduction and function in areas of the brain governing affective responses, emotional processing, motivation, attention and concentration. Although direct-acting antiviral medications lead to high rates of HCV clearance, intracerebral changes may not be subsequently reversed and symptoms of depression, fatigue and neurocognitive deficits may persist. There is an ongoing role for multidisciplinary care and pharmacotherapy to manage these symptoms in HCV patients. Furthermore, there may be opportunities for future therapies to specifically target and ameliorate HCV-associated intracerebral changes.
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Affiliation(s)
- Sern Wei Yeoh
- Department of Gastroenterology, Eastern Health, 3 West, Building B, 8 Arnold St, Box Hill, VIC, 3128, Australia.
| | - Alex C N Holmes
- Department of Psychiatry, University of Melbourne, Level 1 North, Main Block, Royal Melbourne Hospital, 300 Grattan St, Parkville, VIC, 3050, Australia
| | - Michael M Saling
- Melbourne School of Psychological Sciences, 12th Floor, Redmond Barry Building, Parkville Campus, University of Melbourne, Parkville, VIC, Australia, 3010.,Department of Clinical Neuropsychology, Austin Health, Heidelberg Repatriation Hospital, 300 Waterdale Rd, Ivanhoe, VIC, 3079, Australia.,Florey Institute for Neuroscience and Mental Health, 30 Royal Parade, Parkville, VIC, 3052, Australia
| | - Ian P Everall
- Department of Psychiatry, University of Melbourne, Level 1 North, Main Block, Royal Melbourne Hospital, 300 Grattan St, Parkville, VIC, 3050, Australia.,Institute of Psychiatry, Psychology and Neuroscience, Kings College London, 16 De Crespigny Park, London, SE5 8AF, UK.,South London and Maudsley NHS Foundation Trust, Bethlem Royal Hospital, Monks Orchard Road, Beckenham, BR3 3BX, UK
| | - Amanda J Nicoll
- Department of Gastroenterology, Eastern Health, 3 West, Building B, 8 Arnold St, Box Hill, VIC, 3128, Australia.,Department of Gastroenterology and Hepatology, Royal Melbourne Hospital, 300 Grattan St, Parkville, VIC, 3050, Australia
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