Advertisement

Digestive Diseases and Sciences

, Volume 64, Issue 12, pp 3394–3401 | Cite as

Nonalcoholic Fatty Liver Disease Among Individuals with HIV Mono-infection: A Growing Concern?

  • Margaret Morrison
  • Heather Y. Hughes
  • Susanna Naggie
  • Wing-Kin SynEmail author
Review
First Online:
  • 104 Downloads

Abstract

Purpose of Review

Liver disease is a leading cause of non-AIDS-related death in the HIV population since the introduction of highly active antiretroviral treatment (HAART). Recent studies suggest that patients with HIV are at high risk for nonalcoholic fatty liver disease (NAFLD) and progressive liver fibrosis. Evidence for the prevalence, risk factors, and diagnostic methodologies of NAFLD in patients with HIV mono-infection is summarized here.

Recent Findings

Although limited, published studies suggest that the prevalence of NAFLD is higher (30–50%) and progresses at an increased rate in patients with HIV compared to the general population. Identifying those at risk for significant liver fibrosis is critical, preferably with non-invasive screening tests. While there is a paucity of evidence in this population, transient elastography (TE) appears to provide a sensitive, non-invasive screening modality.

Summary

Identifying NAFLD early will allow for dietary and lifestyle interventions, as well as future drug therapies to decrease the risk of progressive liver fibrosis and cirrhosis in the high-risk HIV population. Clinicians should be aware of this risk and consider using TE for NAFLD diagnosis and surveillance.

Keywords

NAFLD NASH HIV Transient elastography 
This is a preview of subscription content, log in to check access.

Notes

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interests.

References

  1. 1.
    Antiretroviral Therapy Cohort Collaboration. Causes of death in HIV-1-infected patients treated with antiretroviral therapy, 1996–2006: collaborative analysis of 13 HIV cohort studies. Clin Infect Dis. 2010;50:1387–1396.Google Scholar
  2. 2.
    Weber R, Sabin CA, Friis-Møller N, et al. Liver-related deaths in persons infected with the human immunodeficiency virus: the D:A:D study. Arch Intern Med. 2006;166:1632–1641.PubMedGoogle Scholar
  3. 3.
    Lewden C, May T, Rosenthal E, et al. Changes in causes of death among adults infected by HIV between 2000 and 2005: The “Mortalité 2000 and 2005” surveys (ANRS EN19 and Mortavic). J Acquir Immune Defic Syndr (1999). 2008;48:590–598.Google Scholar
  4. 4.
    Adams LA, Lymp JF, St Sauver J, et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology. 2005;129:113–121.PubMedGoogle Scholar
  5. 5.
    Luis Calzadilla B, Adams LA. The natural course of non-alcoholic fatty liver disease. Int J Mol Sci. 2016;17:774.Google Scholar
  6. 6.
    Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011;34:274–285.PubMedGoogle Scholar
  7. 7.
    Williams CD, Stengel J, Asike MI, et al. Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study. Gastroenterology. 2011;140:124–131.PubMedGoogle Scholar
  8. 8.
    Marchesini G, Babini M. Nonalcoholic fatty liver disease and the metabolic syndrome. Minerva Cardioangiol. 2006;54:229–239.PubMedGoogle Scholar
  9. 9.
    Pagano G, Pacini G, Musso G, et al. Nonalcoholic steatohepatitis, insulin resistance, and metabolic syndrome: further evidence for an etiologic association. Hepatology (Baltimore, MD). 2002;35:367–372.Google Scholar
  10. 10.
    Armstrong MJ, Adams LA, Canbay A, Syn WK. Extrahepatic complications of nonalcoholic fatty liver disease. Hepatology. 2014;59:1174–1197.PubMedGoogle Scholar
  11. 11.
    Younossi ZM, Stepanova M, Afendy M, et al. Changes in the prevalence of the most common causes of chronic liver diseases in the United States from 1988 to 2008. Clin Gastroenterol Hepatol. 2011;9:524–530.PubMedGoogle Scholar
  12. 12.
    Younossi ZM, Blissett D, Blissett R, et al. The economic and clinical burden of nonalcoholic fatty liver disease in the United States and Europe. Hepatology (Baltimore, MD). 2016;64:1577–1586.Google Scholar
  13. 13.
    Fracanzani AL, Valenti L, Bugianesi E, et al. Risk of severe liver disease in nonalcoholic fatty liver disease with normal aminotransferase levels: a role for insulin resistance and diabetes. Hepatology (Baltimore, MD). 2008;48:792–798.Google Scholar
  14. 14.
    Mofrad P, Contos MJ, Haque M, et al. Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values. Hepatology. 2003;37:1286–1292.PubMedGoogle Scholar
  15. 15.
    Giovanni G, Nicola S, Chiara S, et al. Nonalcoholic fatty liver disease in HIV-infected patients referred to a metabolic clinic: prevalence, characteristics, and predictors. Clin Infect Dis. 2008;47:250–257.Google Scholar
  16. 16.
    Crum-Cianflone N, Dilay A, Collins G, et al. Nonalcoholic fatty liver disease among HIV-infected persons. J Acquir Immune Defic Syndr (1999). 2009;50:464–473.Google Scholar
  17. 17.
    Lombardi R, Sambatakou H, Mariolis I, et al. Prevalence and predictors of liver steatosis and fibrosis in unselected patients with HIV mono-infection. Dig Liver Dis. 2016;48:1471–1477.PubMedGoogle Scholar
  18. 18.
    Vodkin I, Valasek MA, Bettencourt R, Cachay E, Loomba R. Clinical, biochemical and histological differences between HIV-associated NAFLD and primary NAFLD: a case-control study. Aliment Pharmacol Ther. 2015;41:368–378.PubMedGoogle Scholar
  19. 19.
    Morse CG, Matthews L, Kovacs JA, et al. Nonalcoholic steatohepatitis and hepatic fibrosis in HIV-1-monoinfected adults with elevated aminotransferase levels on antiretroviral therapy. Clin Infect Dis. 2015;60:1569–1578.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Vuille-Lessard E, Lebouche B, Lennox L, et al. Nonalcoholic fatty liver disease diagnosed by transient elastography with controlled attenuation parameter in unselected HIV monoinfected patients. AIDS. 2016;30:2635–2643.PubMedGoogle Scholar
  21. 21.
    Lui G, Wong VWS, Wong GLH, et al. Liver fibrosis and fatty liver in Asian HIV-infected patients. Aliment Pharmacol Ther. 2016;44:411–421.PubMedGoogle Scholar
  22. 22.
    Maurice JB, Patel A, Scott AJ, et al. Prevalence and risk factors of nonalcoholic fatty liver disease in HIV-monoinfection. AIDS (London, England). 2017;31:1621–1632.Google Scholar
  23. 23.
    Price JC, Seaberg EC, Post WS, et al. Risk factors for fatty liver in the multicenter AIDS cohort study. Am J Gastroenterol. 2014;109:695–704.PubMedPubMedCentralGoogle Scholar
  24. 24.
    Kardashian A, Ma Y, Scherzer R, et al. Sex differences in the association of HIV infection with hepatic steatosis. AIDS (London, England). 2017;31:365–373.Google Scholar
  25. 25.
    Browning JD, Szczepaniak LS, Dobbins R, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology (Baltimore, MD). 2004;40:1387–1395.Google Scholar
  26. 26.
    Koethe JR, Jenkins CA, Lau B, et al. Rising obesity prevalence and weight gain among adults starting antiretroviral therapy in the United States and Canada. AIDS Res Hum Retrovir. 2016;32:50–58.PubMedGoogle Scholar
  27. 27.
    van der Schouw YT, Peeters PH. Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19·2 million participants. Lancet. 2016;387:10026.Google Scholar
  28. 28.
    Romeo S, Kozlitina J, Xing C, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2008;40:1461–1465.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Liu YL, Patman GL, Leathart JBS, et al. Carriage of the PNPLA3 rs738409 C>G polymorphism confers an increased risk of non-alcoholic fatty liver disease associated hepatocellular carcinoma. J Hepatol. 2014;61:75–81.PubMedGoogle Scholar
  30. 30.
    Sookoian S, Pirola CJ. Meta-analysis of the influence of I148 M variant of patatin-like phospholipase domain containing 3 gene (PNPLA3) on the susceptibility and histological severity of nonalcoholic fatty liver disease. Hepatology (Baltimore, MD). 2011;53:1883–1894.Google Scholar
  31. 31.
    Speliotes EK, Butler JL, Palmer CD, et al. PNPLA3 variants specifically confer increased risk for histologic nonalcoholic fatty liver disease but not metabolic disease. Hepatology (Baltimore, MD). 2010;52:904–912.Google Scholar
  32. 32.
    Bourgi K, Rebeiro PF, Turner M, et al. Greater weight gain in treatment-naive persons starting dolutegravir-based antiretroviral therapy. Clin Infect Dis 2019.  https://doi.org/10.1093/cid/ciz407.
  33. 33.
    Gange SJ, Kitahata MM, Saag MS, et al. Cohort profile: The North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). Int J Epidemiol. 2007;36:294–301.PubMedPubMedCentralGoogle Scholar
  34. 34.
    Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Accessed Aug 2019.
  35. 35.
    Debes JD, Bohjanen PR, Boonstra A. Mechanisms of accelerated liver fibrosis progression during HIV infection. J Clin Transl Hepatol. 2016;4:328–335.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Angulo P, Kleiner DE, Dam-Larsen S, et al. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology. 2015;149:389–397.PubMedPubMedCentralGoogle Scholar
  37. 37.
    Scherer A, ois Dufour J-F. Treatment of non-alcoholic fatty liver disease. Dig Dis. 2016;34:27–31.PubMedGoogle Scholar
  38. 38.
    Thoma C, Day CP, Trenell MI. Lifestyle interventions for the treatment of non-alcoholic fatty liver disease in adults: a systematic review. J Hepatol. 2012;56:255–266.PubMedGoogle Scholar
  39. 39.
    Musso G, Cassader M, Rosina F, Gambino R. Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials. Diabetologia. 2012;55:885–904.PubMedGoogle Scholar
  40. 40.
    Banini BA, Sanyal AJ. Current and future pharmacologic treatment of nonalcoholic steatohepatitis. Curr Opin Gastroenterol. 2017;33:134–141.PubMedPubMedCentralGoogle Scholar
  41. 41.
    Petit JM, Vergès B. GLP-1 receptor agonists in NAFLD. Diabetes Metab. 2017;43:28–30.Google Scholar
  42. 42.
    Patoulias D. SGLT-2 inhibitors: are they a promising treatment option in T2DM patients with NAFLD? Acta Med (Hradec Kralove). 2017;60:167–170.Google Scholar
  43. 43.
    Dongiovanni P, Petta S, Mannisto V, et al. Statin use and non-alcoholic steatohepatitis in at risk individuals. J Hepatol. 2015;63:705–712.PubMedGoogle Scholar
  44. 44.
    Kowdley KV, Wilson LA, Van Natta ML, Pai RK, Sanyal AJ. LP10: Efficacy and safety of vitamin E for nonalcoholic steatohepatitis: combined analysis of three controlled trials. J Hepatol. 2015;62:S268.Google Scholar
  45. 45.
    Friedman SL, Ratziu V, Harrison SA, et al. A randomized, placebo-controlled trial of cenicriviroc for treatment of nonalcoholic steatohepatitis with fibrosis. Hepatology. 2018;67:1754–1767.PubMedPubMedCentralGoogle Scholar
  46. 46.
    Ratziu V, Sanyal AJ, MacConell L, et al. Regenerate: a phase 3, double-blind, randomized, placebo-controlled multicenter study of obeticholic acid therapy for nonalcoholic steatohepatitis. J Hepatol. 2016;64:S294–S295.Google Scholar
  47. 47.
    Intercept. Intercept announces positive topline results from pivotal phase 3 REGENERATE study of obeticholic acid in patients with liver fibrosis due to NASH. 2019. Available at http://ir.interceptpharma.com/node/12371/pdf.
  48. 48.
    Shetty A, Syn WK. Current treatment options for nonalcoholic fatty liver disease. Curr Opin Gastroenterol. 2019;35:168–176.PubMedGoogle Scholar
  49. 49.
    Burke A. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Yearb Gastroenterol. 2006;2006:262–264.Google Scholar
  50. 50.
    Sterling RK, Smith PG, Brunt EM. Hepatic steatosis in human immunodeficiency virus: a prospective study in patients without viral hepatitis, diabetes, or alcohol abuse. J Clin Gastroenterol. 2013;47:182–187.PubMedPubMedCentralGoogle Scholar
  51. 51.
    Ingiliz P, Valantin MA, Duvivier C, et al. Liver damage underlying unexplained transaminase elevation in human immunodeficiency virus-1 mono-infected patients on antiretroviral therapy. Hepatology (Baltimore, MD). 2009;49:436–442.Google Scholar
  52. 52.
    Benmassaoud A, Ghali P, Cox J, et al. Screening for nonalcoholic steatohepatitis by using cytokeratin 18 and transient elastography in HIV mono-infection. PLoS ONE. 2018;13:e0191985.PubMedPubMedCentralGoogle Scholar
  53. 53.
    Lemoine M, Assoumou L, De Wit S, et al. Diagnostic accuracy of noninvasive markers of steatosis, NASH, and liver fibrosis in HIV-monoinfected individuals at risk of nonalcoholic fatty liver disease (NAFLD): results from the ECHAM study. J Acquir Immune Defic Syndr (1999). 2019;80:e86–e94.Google Scholar
  54. 54.
    Prat LI, Roccarina D, Lever R, et al. FRI-465—Aetiology and severity of liver disease in HIV positive patients with suspected NAFLD: lessons from a cohort with available liver biopsies. J Hepatol. 2018;68:S572–S573.Google Scholar
  55. 55.
    Regev A, Berho M, Jeffers LJ, et al. Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection. Am J Gastroenterol. 2002;97:2614–2618.PubMedGoogle Scholar
  56. 56.
    Maharaj B, Bhoora IG. Complications associated with percutaneous needle biopsy of the liver when one, two or three specimens are taken. Postgrad Med J. 1992;68:964–967.PubMedPubMedCentralGoogle Scholar
  57. 57.
    Sumida Y. Limitations of liver biopsy and non-invasive diagnostic tests for the diagnosis of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World J Gastroenterol. 2014;20:475.PubMedPubMedCentralGoogle Scholar
  58. 58.
    Mahady SE, Macaskill P, Craig JC, et al. Diagnostic accuracy of noninvasive fibrosis scores in a population of individuals with a low prevalence of fibrosis. Clin Gastroenterol Hepatol. 2017;15:1453–1460.PubMedGoogle Scholar
  59. 59.
    Wilder J, Patel K. The clinical utility of FibroScan((R)) as a noninvasive diagnostic test for liver disease. Med Devices (Auckl). 2014;7:107–114.Google Scholar
  60. 60.
    Boursier J, Vergniol J, Guillet A, et al. Diagnostic accuracy and prognostic significance of blood fibrosis tests and liver stiffness measurement by FibroScan in non-alcoholic fatty liver disease. J Hepatol. 2016;65:570–578.PubMedGoogle Scholar
  61. 61.
    De Silva S, Li W, Kemos P, et al. Non-invasive markers of liver fibrosis in fatty liver disease are unreliable in people of South Asian descent. Frontl Gastroenterol. 2017;2017:2017–100865.Google Scholar
  62. 62.
    Castéra L, Foucher J, Bernard PH, et al. Pitfalls of liver stiffness measurement: a 5-year prospective study of 13,369 examinations. Hepatology (Baltimore, MD). 2010;51:828–835.Google Scholar
  63. 63.
    Sandrin L, Fourquet B, Hasquenoph J-M, et al. Transient elastography: a new noninvasive method for assessment of hepatic fibrosis. Ultrasound Med Biol. 2003;29:1705–1713.PubMedGoogle Scholar
  64. 64.
    Friedrich-Rust M, Ong MF, Martens S, et al. Performance of transient elastography for the staging of liver fibrosis: a meta-analysis. Gastroenterology. 2008;134:960–974.PubMedGoogle Scholar
  65. 65.
    Corpechot C, El Naggar A, Poujol-Robert A, et al. Assessment of biliary fibrosis by transient elastography in patients with PBC and PSC. Hepatology (Baltimore, MD). 2006;43:1118–1124.Google Scholar
  66. 66.
    Laharie D, Zerbib F, Adhoute X, et al. Diagnosis of liver fibrosis by transient elastography (FibroScan) and non-invasive methods in Crohn’s disease patients treated with methotrexate. Aliment Pharmacol Ther. 2006;23:1621–1628.PubMedGoogle Scholar
  67. 67.
    Morse CG, McLaughlin M, Proschan M, et al. Transient elastography for the detection of hepatic fibrosis in HIV-monoinfected adults with elevated aminotransferases on antiretroviral therapy. AIDS. 2015;29:2297–2302.PubMedPubMedCentralGoogle Scholar
  68. 68.
    Perazzo H, Cardoso SW, Yanavich C, et al. Predictive factors associated with liver fibrosis and steatosis by transient elastography in patients with HIV mono-infection under long-term combined antiretroviral therapy. J Int AIDS Soc. 2018;21:11.Google Scholar
  69. 69.
    Puoti M, Moioli MC, Travi G, Rossotti R. The burden of liver disease in human immunodeficiency virus-infected patients. Semin Liver Dis. 2012;32:103–113.PubMedGoogle Scholar
  70. 70.
    Kaspar MB, Sterling RK. Mechanisms of liver disease in patients infected with HIV. BMJ Open Gastroenterol. 2017;4:e000166.PubMedPubMedCentralGoogle Scholar
  71. 71.
    Allen AM, Talwalkar JA, Van Houten HK, Sangaralingham LR, McCoy RG. Healthcare cost and utilization in nonalcoholic fatty liver disease: real-world data from a large U.S. claims database. Hepatology. 2018;68:2230–2238.PubMedGoogle Scholar
  72. 72.
    Shaker M, Tabbaa A, Albeldawi M, Alkhouri N. Liver transplantation for nonalcoholic fatty liver disease: new challenges and new opportunities. World J Gastroenterol. 2014;20:5320–5330.PubMedPubMedCentralGoogle Scholar

Copyright information

© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2019

Authors and Affiliations

  1. 1.Division of General Internal MedicineMedical University of South CarolinaCharlestonUSA
  2. 2.Section of Infectious Diseases, Department of MedicineRalph H. Johnson VAMCCharlestonUSA
  3. 3.Divison of Infectious Diseases, Department of MedicineMedical University of South CarolinaCharlestonUSA
  4. 4.Division of Infectious Diseases, Department of MedicineDuke University School of MedicineDurhamUSA
  5. 5.Division of Infectious Diseases, Department of MedicineDurham VAMCDurhamUSA
  6. 6.Section of Gastroenterology and HepatologyRalph H. Johnson VAMCCharlestonUSA
  7. 7.Division of Gastroenterology and Hepatology, Department of MedicineMedical University of South CarolinaCharlestonUSA
  8. 8.Department of Physiology, Faculty of Medicine and NursingUniversity of Basque Country UPV/EHULeioaSpain

Personalised recommendations

Cite article

Buy options