Predictive factors associated with liver fibrosis and steatosis by transient elastography in patients with HIV mono-infection under long-term combined antiretroviral therapy

Hugo Perazzo, Sandra W Cardoso, Carolyn Yanavich, Estevão P Nunes, Michelle Morata, Nathalia Gorni, Paula Simplicio da Silva, Claudia Cardoso, Cristiane Almeida, Paula Luz, Valdilea G Veloso, Beatriz Grinsztejn, Hugo Perazzo, Sandra W Cardoso, Carolyn Yanavich, Estevão P Nunes, Michelle Morata, Nathalia Gorni, Paula Simplicio da Silva, Claudia Cardoso, Cristiane Almeida, Paula Luz, Valdilea G Veloso, Beatriz Grinsztejn

Abstract

Introduction: Non-alcoholic fatty liver disease is characterized by the presence of hepatic steatosis and can be associated with fibrosis progression, development of cirrhosis and liver-related complications. Data on the prevalence of liver fibrosis and steatosis in HIV patients remain contradictory in resource-limited settings. We aimed to describe the prevalence and factors associated with liver fibrosis and steatosis in patients with HIV mono-infection under long-term antiretroviral therapy (ART) in Rio de Janeiro, Brazil.

Methods: Clinical assessment, fasting blood collection and liver stiffness measurement (LSM)/controlled attenuation parameter (CAP) by transient elastography were performed on the same day for this cross-sectional study (PROSPEC-HIV study; NCT02542020). Patients with viral hepatitis co-infection, ART-naïve or missing data were excluded. Liver fibrosis and steatosis were defined by LSM ≥ 8.0 kPa and CAP ≥ 248 dB/m respectively. HIV history, cumulative and current ART regimens were evaluated. Multivariate logistic regression models adjusted for age and gender were performed.

Results: In total, 395 patients (60% female; median age of 45 (IQR, 35 to 52) years, body mass index = 25.7 (23.2 to 29.4) kg/m2 , alanine aminotransferase = 30 (23 to 42) IU/L, duration of ART for 7 (4 to 14) years) were included. LSM and CAP were reliable in 93% (n = 367) and 87% (n = 344) respectively. The prevalence of fibrosis and steatosis were 9% (95% confidence interval (CI), 7 to 13) and 35% (95% CI, 30 to 40) respectively. The following factors were associated with fibrosis (odds ratio (OR) (95% CI)): older age (per 10 years; 1.80 (1.27 to 2.55); p = 0.001) and CD4+ count <200 cells/mm3 (7.80 (2.09 to 29.09), p = 0.002). Type 2 diabetes had a trend towards the presence of liver fibrosis (2.67 (0.96 to 7.46), p = 0.061). Central obesity (10.74 (4.40 to 26.20), p < 0.001), type 2 diabetes (9.74 (3.15 to 30.10), p < 0.001), dyslipidaemia (2.61 (1.35 to 5.05), p = 0.003) and metabolic syndrome (4.28 (2.45 to 7.46), p < 0.001) were associated with steatosis. A dominant backbone ART regimen of zidovudine (AZT), d4T, ddI or ddC was associated with steatosis (1.90 (1.07 to 3.38), p = 0.028) independently of metabolic features.

Conclusion: Integrated strategies for preventing non-communicable diseases in people with HIV mono-infection are necessary to decrease the burden of liver diseases. Clinical Trial Number: NCT02542020.

Keywords: HIV infection, HIV care continuum; fatty liver; hepatic fibrosis; liver disease.

© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.

Figures

Figure 1. Study flow chart of patient's…
Figure 1. Study flow chart of patient's recruitment

References

    1. Platt L, Easterbrook P, Gower E, McDonald B, Sabin K, McGowan C, et al. Prevalence and burden of HCV co‐infection in people living with HIV: a global systematic review and meta‐analysis. Lancet Infect Dis. 2016;16(7):797–808.
    1. Maurice JB, Patel A, Scott AJ, Patel K, Thursz M, Lemoine M. Prevalence and risk factors of nonalcoholic fatty liver disease in HIV‐monoinfection. AIDS. 2017;31(11):1621–32.
    1. Diehl AM, Day C. Cause, pathogenesis, and treatment of nonalcoholic steatohepatitis. N Engl J Med. 2017;377(21):2063–72.
    1. Bravo AA, Sheth SG, Chopra S. Liver biopsy. N Engl J Med. 2001;344(7):495–500.
    1. Tsai E, Lee TP. Diagnosis and evaluation of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis, including noninvasive biomarkers and transient elastography. Clin Liver Dis. 2018;22(1):73–92.
    1. Bota S, Herkner H, Sporea I, Salzl P, Sirli R, Neghina AM, et al. Meta‐analysis: ARFI elastography versus transient elastography for the evaluation of liver fibrosis. Liver Int. 2013;33(8):1138–47.
    1. Karlas T, Petroff D, Sasso M, Fan JG, Mi YQ, de Ledinghen V, et al. Individual patient data meta‐analysis of controlled attenuation parameter (CAP) technology for assessing steatosis. J Hepatol. 2017;66(5):1022–30.
    1. Bellentani S. The epidemiology of non‐alcoholic fatty liver disease. Liver Int. 2017;37 Suppl 1:81–4.
    1. Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella MH. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67(1):328–57.
    1. Morse CG, McLaughlin M, Matthews L, Proschan M, Thomas F, Gharib AM, et al. Nonalcoholic steatohepatitis and hepatic fibrosis in HIV‐1‐monoinfected adults with elevated aminotransferase levels on antiretroviral therapy. Clin Infect Dis. 2015;60(10):1569–78.
    1. Mohr R, Schierwagen R, Schwarze‐Zander C, Boesecke C, Wasmuth JC, Trebicka J, et al. Liver fibrosis in HIV patients receiving a modern cART: which factors play a role? Medicine (Baltimore). 2015;94(50):e2127.
    1. Lui G, Wong VW, Wong GL, Chu WC, Wong CK, Yung IM, et al. Liver fibrosis and fatty liver in Asian HIV‐infected patients. Aliment Pharmacol Ther. 2016;44(4):411–21.
    1. Lombardi R, Sambatakou H, Mariolis I, Cokkinos D, Papatheodoridis GV, Tsochatzis EA. Prevalence and predictors of liver steatosis and fibrosis in unselected patients with HIV mono‐infection. Dig Liver Dis. 2016;48(12):1471–7.
    1. Pembroke T, Deschenes M, Lebouche B, Benmassaoud A, Sewitch M, Ghali P, et al. Hepatic steatosis progresses faster in HIV mono‐infected than HIV/HCV co‐infected patients and is associated with liver fibrosis. J Hepatol. 2017;67(4):801–8.
    1. Lemoine M, Lacombe K, Bastard JP, Sebire M, Fonquernie L, Valin N, et al. Metabolic syndrome and obesity are the cornerstones of liver fibrosis in HIV‐monoinfected patients. AIDS. 2017;31(14):1955–64.
    1. Alberti KG, Zimmet P, Shaw J. Metabolic syndrome–a new world‐wide definition. A consensus statement from the International Diabetes Federation. Diabet Med. 2006;23(5):469–80.
    1. Saunders JB, Aasland OG, Babor TF, de la Fuente JR, Grant M. Development of the alcohol use disorders identification test (AUDIT): WHO collaborative project on early detection of persons with harmful alcohol consumption–II. Addiction. 1993;88(6):791–804.
    1. de Ledinghen V, Vergniol J. Transient elastography (FibroScan). Gastroenterol Clin Biol. 2008;32 6 Suppl 1:58–67.
    1. Poynard T, Ingiliz P, Elkrief L, Munteanu M, Lebray P, Morra R, et al. Concordance in a world without a gold standard: a new non‐invasive methodology for improving accuracy of fibrosis markers. Plos One. 2008;3(12):e3857.
    1. Koehler EM, Plompen EP, Schouten JN, Hansen BE, Darwish Murad S, Taimr P, et al. Presence of diabetes mellitus and steatosis is associated with liver stiffness in a general population: The Rotterdam study. Hepatology. 2016;63(1):138–47.
    1. Grinsztejn B, Veloso VG, Friedman RK, Moreira RI, Luz PM, Campos DP, et al. Early mortality and cause of deaths in patients using HAART in Brazil and the United States. AIDS. 2009;23(16):2107–14.
    1. Akinwande MO, Dikko HG, Samson A. Variance inflation factor: as a condition for the inclusion of suppressor variable(s) in regression analysis. Open J Stat. 2015;5:754–67.
    1. Macias J, Real LM, Rivero‐Juarez A, Merchante N, Camacho A, Neukam K, et al. Changes in liver steatosis evaluated by transient elastography with the controlled attenuation parameter in HIV‐infected patients. HIV Med. 2016;17(10):766–73.
    1. Koethe JR, Jenkins CA, Lau B, Shepherd BE, Justice AC, Tate JP, et al. Rising obesity prevalence and weight gain among adults starting antiretroviral therapy in the United States and Canada. AIDS Res Hum Retroviruses. 2016;32(1):50–8.
    1. Glassner A, Eisenhardt M, Kokordelis P, Kramer B, Wolter F, Nischalke HD, et al. Impaired CD4(+) T cell stimulation of NK cell anti‐fibrotic activity may contribute to accelerated liver fibrosis progression in HIV/HCV patients. J Hepatol. 2013;59(3):427–33.
    1. Coghlan ME, Sommadossi JP, Jhala NC, Many WJ, Saag MS, Johnson VA. Symptomatic lactic acidosis in hospitalized antiretroviral‐treated patients with human immunodeficiency virus infection: a report of 12 cases. Clin Infect Dis. 2001;33(11):1914–21.
    1. Grattagliano I, de Bari O, Bernardo TC, Oliveira PJ, Wang DQ, Portincasa P. Role of mitochondria in nonalcoholic fatty liver disease–from origin to propagation. Clin Biochem. 2012;45(9):610–8.
    1. Caron‐Debarle M, Boccara F, Lagathu C, Antoine B, Cervera P, Bastard JP, et al. Adipose tissue as a target of HIV‐1 antiretroviral drugs. Potential consequences on metabolic regulations. Curr Pharm Des. 2010;16(30):3352–60.
    1. World Health Organization . Progress report 2011: Global HIV/AIDS response. Epidemic update and health sector progress towards universal access. 2011. [cited 2018 Mar 22]. Available from:
    1. Franzeck FC, Letang E, Mwaigomole G, Jullu B, Glass TR, Nyogea D, et al. cART prescription trends in a prospective HIV cohort in rural Tanzania from 2007 to 2011. BMC Infect Dis. 2014;14:90.
    1. Macias J, Mancebo M, Merino D, Tellez F, Montes‐Ramirez ML, Pulido F, et al. Changes in liver steatosis after switching from efavirenz to raltegravir among human immunodeficiency virus‐infected patients with nonalcoholic fatty liver disease. Clin Infect Dis. 2017;65(6):1012–9.
    1. Ministério da Saúde do Brasil: Guideline for management and treatment of HIV infection in adults [Protocolo Clínico e Diretrizes Terapêuticas para manejo da infecção pelo HIV em adultos], Brazilian Ministry of Health [Ministério da Saude do Brasil]. 2017. [cited 2018 Mar 22]. Available from:
    1. Bedossa P, Dargere D, Paradis V. Sampling variability of liver fibrosis in chronic hepatitis C. Hepatology. 2003;38(6):1449–57.
    1. Fernandes FF, Perazzo H, Andrade LE, Dellavance A, Terra C, Pereira G, et al. Latent class analysis of noninvasive methods and liver biopsy in chronic hepatitis C: an approach without a gold standard. Biomed Res Int. 2017;2017:8252980.
    1. Loomba R. Role of imaging based biomarkers in NAFLD: recent advances in clinical application and future research directions. J Hepatol. 2017;68(2):296–304.
    1. Morse CG, McLaughlin M, Proschan M, Koh C, Kleiner DE, Heller T, et al. Transient elastography for the detection of hepatic fibrosis in HIV‐monoinfected adults with elevated aminotransferases on antiretroviral therapy. AIDS. 2015;29(17):2297–302.
    1. Price JC, Dodge JL, Ma Y, Scherzer R, Korn N, Tillinghast K, et al. Controlled attenuation parameter and magnetic resonance spectroscopy‐measured liver steatosis are discordant in obese HIV‐infected adults. AIDS. 2017;31(15):2119–25.
    1. Perazzo H, Fernandes FF, Gomes A, Terra C, Perez RM, Figueiredo FA. Interobserver variability in transient elastography analysis of patients with chronic hepatitis C. Liver Int. 2015;35(5):1533–9.
    1. Perazzo H, Veloso VG, Grinsztejn B, Hyde C, Castro R. Factors that could impact on liver fibrosis staging by transient elastography. Int J Hepatol. 2015;2015:624596.
    1. Wong VW, Petta S, Hiriart JB, Camma C, Wong GL, Marra F, et al. Validity criteria for the diagnosis of fatty liver by M probe‐based controlled attenuation parameter. J Hepatol. 2017;67(3):577–84.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren