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Liver fibrosis is associated with cognitive impairment in people living with HIV

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Abstract

Purpose

Our aim was to better explore the association between liver fibrosis (LF) and neurocognitive impairment (NCI) in people living with HIV (PLWH).

Methods

We performed a cross-sectional cohort study by consecutively enrolling PLWH at two clinical centers. All subjects underwent a comprehensive neuropsychological battery; NCI was defined as having a pathological performance (1.5 SD below the normative mean) on at least two cognitive domains. LF was explored using FIB4 index; in a subgroup of PLWH, LF was also assessed by transient elastography.

Results

A total of 386 subjects were enrolled, of whom 17 (4.4%) had FIB4 > 3.25. In the subgroup of PLWH (N = 127) performing also liver transient elastography, 14 (11%) had liver stiffness > 14 kPa. Overall, 47 subjects (12%) were diagnosed with NCI. At multivariate regression analyses, participants with FIB4 > 1.45 showed a higher risk of NCI in comparison with those with lower values (aOR 3.04, p = 0.044), after adjusting for education (aOR 0.71, p < 0.001), past AIDS-defining events (aOR 2.91, p = 0.014), CD4 cell count, past injecting drug use (IDU), HIV-RNA < 50 copies/mL, and HCV co-infection. Also a liver stiffness > 14 kPa showed an independent association with a higher risk of NCI (aOR 10.13, p = 0.041). Analyzing any single cognitive domain, a higher risk of abnormal psychomotor speed was associated with a liver stiffness > 14 kPa (aOR 223.17, p = 0.019) after adjusting for education (aOR 0.57, p = 0.018), HIV-RNA < 50 copies/mL (aOR 0.01, p = 0.007), age, past IDU, and HCV co-infection.

Conclusions

In PLWH, increased LF, estimated through non-invasive methods, was associated to a higher risk of NCI independently from HCV status.

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References

  1. Ciccarelli N, Fabbiani M, Grima P, et al. Comparison of cognitive performance in HIV or HCV mono-infected and HIV–HCV co-infected patients. Infection. 2013;41:1103–9.

    Article  CAS  PubMed  Google Scholar 

  2. Clifford DB, Vaida F, Kao YT, CHARTER Group, et al. Absence of neurocognitive effect of hepatitis C infection in HIV-coinfected people. Neurology. 2015;84:241–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Laskus T, Radkowski M, Adair DM, et al. Emerging evidence of hepatitis C virus neuroinvasion. AIDS 2005;Suppl 3:S140–4 (review).

    Article  Google Scholar 

  4. Valcour VG, Rubin LH, Obasi MU, Womenʼs Interagency HIV Study Protocol Team, et al. Liver fibrosis linked to cognitive performance in HIV and hepatitis C. J Acquir Immune Defic Syndr. 2016;72:266–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Sterling RK, Lissen E, Clumeck N, APRICOT Clinical Investigators, et al. Development of a simple non-invasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006;43:1317–25.

    Article  CAS  PubMed  Google Scholar 

  6. Poynard T, Ratziu V, Bedossa P. Appropriateness of liver biopsy. Can J Gastroenterol. 2000;14:543–8 (review).

    Article  CAS  PubMed  Google Scholar 

  7. Bravo AA, Sheth SG, Chopra S. Liver biopsy. N Engl J Med. 2001;344:495–500 (review).

    Article  CAS  PubMed  Google Scholar 

  8. Mehta SH, Buckle GC. Assessment of liver disease (non-invasive methods). Curr Opin HIV AIDS. 2011;6:465–71.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Mendeni M, Focà E, Gotti D, et al. Evaluation of liver fibrosis: concordance analysis between non-invasive scores (APRI and FIB-4) evolution and predictors in a cohort of HIV-infected patients without hepatitis C and B infection. Clin Infect Dis. 2011;52:1164–73.

    Article  PubMed  Google Scholar 

  10. Sanchez-Conde M, Montes-Ramirez ML, Miralles P, et al. Comparison of transient elastography and liver biopsy for the assessment of liver fibrosis in HIV/hepatitis C virus-coinfected patients and correlation with non-invasive serum markers. J Viral Hepat. 2010;17:280–6.

    Article  CAS  PubMed  Google Scholar 

  11. Carlesimo GA, Caltagirone C, Gainotti G. The Mental Deterioration Battery: normative data, diagnostic reliability and qualitative analyses of cognitive impairment. The Group for the Standardization of the Mental Deterioration Battery. Eur Neurol. 1996;36:378–84.

    Article  CAS  PubMed  Google Scholar 

  12. Orsini A, Grossi D, Capitani E, Laiacona M, Papagno C, Vallar G. Verbal and spatial immediate memory span: normative data from 1355 adults and 1112 children. Ital J Neurol Sci. 1987;8:539–48.

    Article  CAS  PubMed  Google Scholar 

  13. Orsini A, Laicardi C. WAIS-R. Contributo alla taratura italiana. Firenze: Giunti OS; 1997.

    Google Scholar 

  14. Heaton RK, Grant I, Matthews CG. Comprehensive norms for an expanded Halstead–Reitan battery: demographic corrections, research findings, and clinical applications. Odessa: Psychological Assessment Resources, Inc.; 1991.

    Google Scholar 

  15. Antinori A, Arendt G, Becker JT, et al. Updated research nosology for HIV-associated neurocognitive disorders. Neurology. 2007;69:1789–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Gisslén M, Price RW, Nilsson S. The definition of HIV-associated neurocognitive disorders: are we overestimating the real prevalence? BMC Infect Dis. 2011;11:356.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Torti C, Focà E, Cesana BM, Lescure FX. Asymptomatic neurocognitive disorders in patients infected by HIV: fact or fiction? BMC Med. 2011;9:138.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Valcour V, Shikuma C, Shiramizu B, et al. Higher frequency of dementia in older HIV-1 individuals: the Hawaii aging with HIV-1 cohort. Neurology. 2004;63:822–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ciccarelli N, Fabbiani M, Baldonero E, et al. Effect of aging and human immunodeficiency virus infection on cognitive abilities. J Am Geriatr Soc. 2012;60:2048–55.

    Article  PubMed  Google Scholar 

  20. Milanini B, Ciccarelli N, Fabbiani M, et al. Cognitive reserve and neuropsychological functioning in older HIV-infected people. J Neurovirol. 2016;22:575–83.

    Article  PubMed  Google Scholar 

  21. Sebastiani G, Gkouvatsos K, Pantopoulos K. Chronic hepatitis C and liver fibrosis. World J Gastroenterol. 2014;20:11033–1153.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. McCrea M, Cordoba J, Vessey G, Blei AT, Randolph C. Neuropsychological characterization and detection of subclinical hepatic encephalopathy. Arch Neurol. 1996;53:758–63.

    Article  CAS  PubMed  Google Scholar 

  23. Lauridsen MM, Jepsen P, Vilstrup H. Critical flicker frequency and continuous reaction times for the diagnosis of minimal hepatic encephalopathy: a comparative study of 154 patients with liver disease. Metab Brain Dis. 2011;26:135–9.

    Article  PubMed  Google Scholar 

  24. Falasca K, Reale M, Ucciferri C, et al. Cytokines, hepatic fibrosis, and antiretroviral therapy role in neurocognitive disorders HIV related. AIDS Res Hum Retroviruses. 2017;33:246–53.

    Article  CAS  PubMed  Google Scholar 

  25. Tarter RE, Edwards KL, Van Thiel DH. Neuropsychological dysfunction due to liver disease. In: Tarter RE, Van Thiel DH, Edwardsm KL, editors. Medical neuropsychology. New York: Plenum Press; 1989. pp. 75–97.

    Google Scholar 

  26. Hilsabeck RC, Perry W, Hassanein TI. Neuropsychological impairment in patients with chronic hepatitis C. Hepatology. 2002;35:440–6.

    Article  PubMed  Google Scholar 

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Acknowledgements

No specific funding was received for this study.

Author information

Author notes

  1. Nicoletta Ciccarelli

    Present address: Department of Psychology, Catholic University, Largo Agostino Gemelli 1, 20123, Milan, Italy

  2. Massimiliano Fabbiani

    Present address: Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

  3. Roberta Gagliardini

    Present address: Infectious Diseases Unit, Department of Medical Biotechnologies, Siena University Hospital, University of Siena, Siena, Italy

Authors and Affiliations

  1. Institute of Clinical Infectious Diseases, Catholic University of Sacred Heart, Rome, Italy

    Nicoletta Ciccarelli, Massimiliano Fabbiani, Anna C. Brita, Ramona De Marco, Roberta Gagliardini, Alberto Borghetti, Roberto Cauda & Simona Di Giambenedetto

  2. Division of Infectious Diseases, ‘S. Caterina Novella’ Hospital, Galatina, Italy

    Pierfrancesco Grima

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  1. Nicoletta Ciccarelli
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Corresponding author

Correspondence to Nicoletta Ciccarelli.

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Conflict of interest

M. F. received speakers’ honoraria and support for travel to meetings from Bristol-Myers Squibb (BMS), Gilead, Merck Sharp & Dohme (MSD), ViiV Healthcare, Janssen-Cilag (JC), and fees for attending advisory boards from BMS and Gilead; A.B. reports personal fees and non-financial support from ViiV Healthcare, Gilead Sciences, Inc., grants and non-financial support from Bristol-Myers Squibb, and JC. R.C. has been an advisor for Gilead, JC and Basel Pharmaceutical, and received speakers’ honoraria from ViiV, BMS, MSD, Abbott, Gilead and JC; S. D. G. received speakers’ honoraria and support for travel to meetings from Gilead, Bristol-Myers Squibb (BMS), Abbott, Boehringer Ingelheim, Janssen-Cilag (JC) and GlaxoSmithKline. All other authors: none to declare.

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Ciccarelli, N., Fabbiani, M., Brita, A.C. et al. Liver fibrosis is associated with cognitive impairment in people living with HIV. Infection 47, 589–593 (2019). https://doi.org/10.1007/s15010-019-01284-8

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  • DOI: https://doi.org/10.1007/s15010-019-01284-8

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