Direct antivirals and cognitive impairment in hepatitis C: a clinical-neurophysiologic study
Tóm tắt
Cognition was assessed in hepatitis C virus (HCV) patients, who did not meet the criteria for a minimal hepatic encephalopathy. Their liver function was compensated. We then disentangled potential cognitive changes associated with a sustained virologic response at 12 weeks (SVR-12), following treatment with direct antiviral agents (DAAs). We studied 23 selected HCV patients with a battery of standard neuropsychological tests, and with recordings of the P300 wave, a cerebral potential of “cognitive” significance. There was a baseline evaluation (T0) and a second one 6 months later (T1). We had 2 control groups of comparable age and sex, i.e., 15 patients suffering from non-alcoholic fatty liver disease (NAFLD) and 15 healthy subjects. At T0, we detected a significant (p < 0.05) cognitive impairment in the HCV group, which involved episodic and working memory, attention, visuospatial and verbal abilities, executive functions, and logic reasoning. The P300 latency was significantly (p < 0.05) delayed in the group. At T1, we observed some significant (p < 0.05) HCV recovery in given test domains, e.g., memory, executive functions, and reasoning. Accordingly, the P300 latency shortened significantly (p < 0.05). HCV patients exhibited subtle cognitive defects, somehow independent of their liver condition, possibly linked to direct or indirect brain involvement by the virus. These defects partly recovered following the SVR-12, as achieved through DAAs. The P300 wave was a valid neurophysiologic counterpart of these changes. DAAs can have a role in the early preservation of cognition in HCVs.
Tài liệu tham khảo
Amodio P, Montagnese S (2015) Clinical neurophysiology of hepatic encephalopathy. J Clin Exp Hepatol 5:S60–S68
Amodio P, Valenti P, Del Piccolo F, Pellegrini A, Schiff S, Angeli P, Poci C, Mapelli D, Iannizzi P, Gatta A (2005) P300 latency for the diagnosis of minimal hepatic encephalopathy: evidence that spectral EEG analysis and psychometric tests are enough. Dig Liver Dis 37:861–868
Borkowski JG, Benton AL, Spreen O (1967) Word fluency and brain damage. Neuropsychologia 5:135–140
Byrnes V, Miller A, Lowry D, Hill E, Weinstein C, Alsop D, Lenkinski R, Afdhal NH (2012) Effects of anti-viral therapy and HCV clearance on cerebral metabolism and cognition. J Hepatol 56:549–556
Child CG, Turcotte JG (1964) Surgery and portal hypertension. Major Probl Clin Surg 1:1–85
Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, Harrison SA, Brunt EM, Sanyal AJ (2018) The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Hepatology 67:328–357
Chen J, Florian J, Carter W, Fleischer RD, Hammerstrom TS, Jadhav PR, Zeng W, Murray J, Birnkrant D (2013) Earlier sustained virologic response end points for regulatory approval and dose selection of hepatitis C therapies. Gastroenterology 144:1450–1455
Diamond A (2013) Executive functions. Annu Rev Psychol 64:135–168
Dirks M, Pflugrad H, Haag K, Tillmann HL, Wedemeyer H, Arvanitis D, Hecker H, Tountopoulou A, Goldbecker A, Worthmann H, Weissenborn K (2017) Persistent neuropsychiatric impairment in HCV patients despite clearance of the virus?! J Viral Hepat 24:541–550
Duncan CC, Barry RJ, Connolly JF, Fischer C, Michie PT, Näätänen R, Polich J, Reinvang I, Van Petten C (2009) Event-related potentials in clinical research: guidelines for eliciting, recording, and quantifying mismatch negativity, P300, and N400. Clin Neurophysiol 120:1883–1908
Fath-Elbab HK, Ahmed E, Mansour DF, Soliman WT (2018) Event-related evoked potential versus clinical tests in assessment of subclinical cognitive impairment in chronic hepatitis C virus. Egypt J Neurol Psychiatry Neurosurg 54:35
Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198
Fontana RJ, Bieliauskas LA, Back-Madruga C, Lindsay KL, Kronfol Z, Lok AS, Padmanabhan L, HALT-C Trial Group (2005) Cognitive function in hepatitis C patients with advanced fibrosis enrolled in the HALT-C trial. J Hepatol 43:614–622
Fortini I, Arouca EMG, Tengam FM, Nitrini R (2019) Chronic HCV infection and neuropsychiatric dysfunction. eNeurologicalSci 17:100206
Guerit JM, Amantini A, Fischer C, Kaplan PW, Mecarelli O, Schnitzler A, Ubiali E, Amodio P, members of the ISHEN commission on Neurophysiological Investigations (2009) Neurophysiological investigations of hepatic encephalopathy: ISHEN practice guidelines. Liver Int 29:789–796
Spinnler H, Tognoni G (1987) Italian standardization and classification of neuropsychological tests. Ital J Neurol Sci 6:1–120
Hamdy HSE, Abd El Hamid MSE, Shafik MA, Soliman EMAM (2018) Impact of direct acting antiviral drugs (DAADs) on cognitive function among hepatitis C virus infected patients. Egypt J Hosp Med 73:5743–5747
Heeren M, Weissenborn K, Arvanitis D, Bokemeyer M, Goldbecker A, Tountopoulou A, Peschel T, Grosskreutz J, Hecker H, Buchert R, Berding G (2011) Cerebral glucose utilisation in hepatitis C virus infection-associated encephalopathy. J Cereb Blood Flow Metab 31:2199–2208
Hilsabeck RC, Perry W, Hassanein TI (2002) Neuropsychological impairment in patients with chronic hepatitis C. Hepatology 35:440–446
Huckans M, Seelye A, Parcel T, Mull L, Woodhouse J, Bjornson D, Fuller BE, Loftis JM, Morasco BJ, Sasaki AW, Storzbach D, Hauser P (2009) The cognitive effects of hepatitis C in the presence and absence of a history of substance use disorder. J Int Neuropsychol Soc 15:69–82
Juanbeltz R, Martínez-Baz I, San Miguel R, Goñi-Esarte S, Cabasés JM, Castilla J (2018) Impact of successful treatment with directacting antiviral agents on health-related quality of life in chronic hepatitis C patients. PLoS One 13:e0205277
Kleefeld F, Heller S, Ingiliz P, Jessen H, Petersen A, Kopp U, Kraft A, Hahn K (2018) Interferon-free therapy in hepatitis C virus (HCV) monoinfected and HCV/HIV coinfected patients: effect on cognitive function, fatigue, and mental health. J Neuro-Oncol 24:557–569
Kramer L, Bauer E, Funk G, Hofer H, Jessner W, Steindl-Munda P, Wrba F, Madl C, Gangl A, Ferenci P (2002) Subclinical impairment of brain function in chronic hepatitis C infection. J Hepatol 37:349–354
Kraus MR, Schäfer A, Teuber G, Porst H, Sprinzl K, Wollschläger S, Keicher C, Scheurlen M (2013) Improvement of neurocognitive function in responders to an antiviral therapy for chronic hepatitis C. Hepatology 58:497–504
Letendre S, Paulino AD, Rockenstein E, Adame A, Crews L, Cherner M, Heaton R, Ellis R, Everall IP, Grant I, Masliah E, HIV Neurobehavioral Research Center Group (2007) Pathogenesis of hepatitis C virus coinfection in the brains of patients infected with HIV. J Infect Dis 196:361–370
Lowry D, Coughlan B, McCarthy O, Crowe J (2010) Investigating health-related quality of life, mood and neuropsychological test performance in a homogeneous cohort of Irish female hepatitis C patients. J Viral Hepat 17:352–359
Marra C, Ferraccioli M, Gainotti G (2007) Gender-related dissociations of categorical fluency in normal subjects and in subjects with Alzheimer’s disease. Neuropsychology 21:207–211
McAndrews MP, Farcnik K, Carlen P, Damyanovich A, Mrkonjic M, Jones S, Heathcote EJ (2005) Prevalence and significance of neurocognitive dysfunction in hepatitis C in the absence of correlated risk factors. Hepatology 41:801–808
Monaco S, Mariotto S, Ferrari S, Calabrese M, Zanusso G, Gajofatto A, Sansonno D, Dammacco F (2015) Hepatitis C virus-associated neurocognitive and neuropsychiatric disorders: advances in 2015. World J Gastroenterol 21:11974–11983
Osterrieth PA (1944) Filetest de copie d’une figure complex: contribution a l’etude de la perception et de la memoire [the test of copying a complex figure: a contribution to the study of perception and memory]. Arch Psychol (Geneve) 30:286–356
Pecoraro V, Banzi R, Cariani E, Chester J, Villa E, D'Amico R, Bertele V, Trenti T (2019) New direct-acting antivirals for the treatment of patients with hepatitis C virus infection: a systematic review of randomized controlled trials. J Clin Exp Hepatol 9:522–538
Picton TW (1992) The P300 wave of the human event-related potential. J Clin Neurophysiol 9:456–479
Rey A (1964) L’examen clinique en psychologie. Presses universitaires de France, Paris
Thames AD, Castellon SA, Singer EJ, Nagarajan R, Sarma MK, Smith J, Thaler NS, Truong JH, Schonfeld D, Thomas MA, Hinkin CH (2015) Neuroimaging abnormalities, neurocognitive function, and fatigue in patients with hepatitis C. Neurol Neuroimmunol Neuroinflamm 2:e59
Thein HH, Maruff P, Krahn MD, Kaldor JM, Koorey DJ, Brew BJ, Dore GJ (2007) Improved cognitive function as a consequence of hepatitis C virus treatment. HIV Med 8:520–528
Volpato S, Montagnese S, Zanetto A, Turco M, De Rui M, Ferrarese A, Amodio P, Germani G, Senzolo M, Gambato M, Russo FP, Burra P (2017) Neuropsychiatric performance and treatment of hepatitis C with direct-acting antivirals: a prospective study. BMJ Open Gastroenterol 4:e000183
Wechsler D (1958) The measurement and appraisal of adult intelligence, 4th edn. William & Wilkins, Baltimore
Weissenborn K (2015) Diagnosis of minimal hepatic encephalopathy. J Clin Exp Hepatol 5:S54–S59
Weissenborn K, Ennen JC, Bokemeyer M, Ahl B, Wurster U, Tillmann H, Trebst C, Hecker H, Berding G (2006) Monoaminergic neurotransmission is altered in hepatitis C virus infected patients with chronic fatigue and cognitive impairment. Gut 55:1624–1630
Weissenborn K, Ennen JC, Schomerus H, Rückert N, Hecker H (2001) Neuropsychological characterization of hepatic encephalopathy. J Hepatol 34:768–773
Wijdicks EFM (2016) Hepatic encephalopathy. N Engl J Med 375:1660–1670
Yarlott L, Heald E, Forton D (2017) Hepatitis C virus infection, and neurological and psychiatric disorders – a review. J Adv Res 8:139–148
Yeoh SW, Holmes ACN, Saling MM, Everall IP, Nicoll AJ (2018) Depression, fatigue and neurocognitive deficits in chronic hepatitis C. Hepatol Int 12:294–304