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Use of Non-invasive Testing to Stage Liver Fibrosis in Patients with HIV

  • Co-infections and Comorbidity (S Naggie, Section Editor)
  • Published:
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Abstract

Patients with HIV have a proclivity to develop liver fibrosis, especially when associated with other conditions such as HCV, HBV, and NAFLD. Identifying HIV-infected patients with significant fibrosis or cirrhosis plays an important role in clinical and therapeutic decision-making. Liver biopsy is currently considered as the gold standard for fibrosis assessment but carries many shortcomings (cost, invasiveness, complications, false negative rate of 20 %). Multiple non-invasive methods of liver fibrosis assessment have been developed, but not all have been studied in HIV-infected individuals. Non-invasive liver fibrosis tools include both serologic-based testing scores (rely on direct and/or indirect markers) such as APRI, FIB4, FibroTest, FibroSpect II, HepaScore, or imaging-based methods such as vibration controlled liver elastography. There is validated data to support the use of non-invasive modalities of fibrosis assessment in HIV-HCV co-infected individuals for the exclusion of cirrhosis, but may be poorly reliable or not enough data exists for the assessment of other co-morbid disease processes.

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References

  1. Puoti M et al. Hepatitis B virus co-infection in human immunodeficiency virus-infected subjects. AIDS Rev. 2002;4(1):27–35.

    PubMed  Google Scholar 

  2. Staples Jr CT, Rimland D, Dudas D. Hepatitis C in the HIV (human immunodeficiency virus) Atlanta V.A. (Veterans Affairs Medical Center) Cohort Study (HAVACS): the effect of coinfection on survival. Clin Infect Dis. 1999;29(1):150-–4.

    Article  PubMed  Google Scholar 

  3. Sulkowski MS, Thomas DL. Hepatitis C in the HIV-infected Person. Ann Intern Med. 2003;138(3):197–207.

    Article  PubMed  Google Scholar 

  4. Guaraldi G et al. Nonalcoholic fatty liver disease in hiv-infected patients referred to a metabolic clinic: prevalence, characteristics, and predictors. Clin Infect Dis. 2008;47(2):250–7.

    Article  PubMed  Google Scholar 

  5. Thio CL et al. HIV-1, hepatitis b virus, and risk of liver-related mortality in the multicenter cohort study (MACS). Lancet. 2002;360(9349):1921–6.

    Article  PubMed  Google Scholar 

  6. Rosen HR. Clinical practice. Chronic hepatitis C infection. N Engl J Med. 2011;364(25):2429–38.

    Article  CAS  PubMed  Google Scholar 

  7. Thein HH et al. Natural history of hepatitis c virus infection in HIV-infected individuals and the impact of hiv in the era of highly active antiretroviral therapy: a meta-analysis. AIDS. 2008;22(15):1979–91.

    Article  PubMed  Google Scholar 

  8. Konerman MA et al. Fibrosis progression in human immunodeficiency virus/hepatitis C virus coinfected adults: prospective analysis of 435 liver biopsy pairs. Hepatology. 2014;59(3):767–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Macias J et al. Fast fibrosis progression between repeated liver biopsies in patients coinfected with human immunodeficiency virus/hepatitis C virus. Hepatology. 2009;50(4):1056–63.

    Article  CAS  PubMed  Google Scholar 

  10. European Association for Study of, L. EASL recommendations on treatment of hepatitis C 2015. J Hepatol. 2015;63(1):199–236.

    Article  Google Scholar 

  11. Zoulim F et al. Hepatitis C virus treatment in the real world: optimising treatment and access to therapies. Gut. 2015;64(11):1824–33.

    Article  CAS  PubMed  Google Scholar 

  12. Do A et al. Drug authorization for sofosbuvir/ledipasvir (harvoni) for chronic HCV infection in a real-world cohort: a new barrier in the HCV care cascade. PLoS One. 2015;10(8):e0135645.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Canary LA, Klevens RM, Holmberg SD. Limited access to new hepatitis C virus treatment under state medicaid programs. Ann Intern Med. 2015;163(3):226–8.

    Article  PubMed  Google Scholar 

  14. Panel AIHG. Hepatitis C guidance: AASLD-idsa recommendations for testing, managing, and treating adults infected with hepatitis C virus. Hepatology. 2015;62(3):932–54.

    Article  Google Scholar 

  15. Sebastiani G, Gkouvatsos K, Pantopoulos K. Chronic hepatitis C and liver fibrosis. World J Gastroenterol. 2014;20(32):11033–53.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Castera L. Noninvasive methods to assess liver disease in patients with hepatitis B or C. Gastroenterology. 2012;142(6):1293–302. e4.

    Article  PubMed  Google Scholar 

  17. Rockey DC et al. Liver biopsy. Hepatology. 2009;49(3):1017–44.

    Article  PubMed  Google Scholar 

  18. Poniachik J et al. The role of laparoscopy in the diagnosis of cirrhosis. Gastrointest Endosc. 1996;43(6):568–71.

    Article  CAS  PubMed  Google Scholar 

  19. Afdhal NH. Diagnosing fibrosis in hepatitis C: Is the pendulum swinging from biopsy to blood tests? Hepatology. 2003;37(5):972–4.

    Article  PubMed  Google Scholar 

  20. Kelleher TB et al. Prediction of hepatic fibrosis in HIV/HCV co-infected patients using serum fibrosis markers: the SHASTA index. J Hepatol. 2005;43(1):78–84.

    Article  PubMed  Google Scholar 

  21. Rossi E et al. Validation of the FibroTest biochemical markers score in assessing liver fibrosis in hepatitis C patients. Clin Chem. 2003;49(3):450–4.

    Article  CAS  PubMed  Google Scholar 

  22. Forns X et al. Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model. Hepatology. 2002;36(4 Pt 1):986–92.

    Article  PubMed  Google Scholar 

  23. Lin ZH et al. Performance of the aspartate aminotransferase-to-platelet ratio index for the staging of hepatitis C-related fibrosis: an updated meta-analysis. Hepatology. 2011;53(3):726–36.

    Article  PubMed  Google Scholar 

  24. Shaheen AA, Myers RP. Diagnostic accuracy of the aspartate aminotransferase-to-platelet ratio index for the prediction of hepatitis C-related fibrosis: a systematic review. Hepatology. 2007;46(3):912–21.

    Article  PubMed  Google Scholar 

  25. Sterling RK et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006;43(6):1317–25.

    Article  CAS  PubMed  Google Scholar 

  26. Christensen C et al. Diagnostic accuracy of a fibrosis serum panel (FIBROSpect II) compared with Knodell and Ishak liver biopsy scores in chronic hepatitis C patients. J Viral Hepat. 2006;13(10):652–8.

    Article  CAS  PubMed  Google Scholar 

  27. Adams LA et al. Hepascore: an accurate validated predictor of liver fibrosis in chronic hepatitis C infection. Clin Chem. 2005;51(10):1867–73.

    Article  CAS  PubMed  Google Scholar 

  28. Cales P et al. A novel panel of blood markers to assess the degree of liver fibrosis. Hepatology. 2005;42(6):1373–81.

    Article  PubMed  Google Scholar 

  29. Lichtinghagen R et al. The enhanced liver fibrosis (ELF) score: normal values, influence factors and proposed cut-off values. J Hepatol. 2013;59(2):236–42.

    Article  PubMed  Google Scholar 

  30. Schmid P et al. Progression of liver fibrosis in HIV/hcv co-infection: a comparison between non-invasive assessment methods and liver biopsy. PLoS One. 2015;10(9):e0138838.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Myers RP et al. Serum biochemical markers accurately predict liver fibrosis in HIV and hepatitis C virus co-infected patients. AIDS. 2003;17(5):721–5.

    Article  CAS  PubMed  Google Scholar 

  32. Sulkowski MS et al. Elevated liver enzymes following initiation of antiretroviral therapy. JAMA. 2000;283(19):2526–7.

    Article  PubMed  Google Scholar 

  33. Macias J et al. Prediction of liver fibrosis in human immunodeficiency virus/hepatitis C virus coinfected patients by simple non-invasive indexes. Gut. 2006;55(3):409–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Loko MA et al. Validation and comparison of simple noninvasive indexes for predicting liver fibrosis in HIV-HCV-coinfected patients: ANRS CO3 aquitaine cohort. Am J Gastroenterol. 2008;103(8):1973–80.

    Article  CAS  PubMed  Google Scholar 

  35. Cacoub P et al. Comparison of non-invasive liver fibrosis biomarkers in HIV/HCV co-infected patients: the fibrovic study—ANRS HC02. J Hepatol. 2008;48(5):765–73.

    Article  PubMed  Google Scholar 

  36. Macias J et al. Use of simple noninvasive biomarkers to predict liver fibrosis in HIV/HCV coinfection in routine clinical practice. HIV Med. 2010;11(7):439–47.

    CAS  PubMed  Google Scholar 

  37. Cales P et al. Comparison of liver fibrosis blood tests developed for HCV with new specific tests in HIV/HCV co-infection. J Hepatol. 2010;53(2):238–44.

    Article  PubMed  Google Scholar 

  38. Kliemann DA et al. Biochemical non-invasive assessment of liver fibrosis cannot replace biopsy in HIV-HCV coinfected patients. Ann Hepatol. 2015;15(1):27–32.

    Article  Google Scholar 

  39. Ahmad W et al. A comparison of four fibrosis indexes in chronic HCV: development of new fibrosis-cirrhosis index (FCI). BMC Gastroenterol. 2011;11:44.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Cole JL et al. Ineffective platelet production in thrombocytopenic human immunodeficiency virus-infected patients. Blood. 1998;91(9):3239–46.

    CAS  PubMed  Google Scholar 

  41. Kontorinis N, Dieterich D. Hepatotoxicity of antiretroviral therapy. AIDS Rev. 2003;5(1):36–43.

    PubMed  Google Scholar 

  42. Bonacini M. Liver injury during highly active antiretroviral therapy: the effect of hepatitis C coinfection. Clin Infect Dis. 2004;38 Suppl 2:S104–8.

    Article  CAS  PubMed  Google Scholar 

  43. Rivero A, Mira JA, Pineda JA. Liver toxicity induced by non-nucleoside reverse transcriptase inhibitors. J Antimicrob Chemother. 2007;59(3):342–6.

    Article  CAS  PubMed  Google Scholar 

  44. Wilder J, Patel K. The clinical utility of FibroScan((R)) as a noninvasive diagnostic test for liver disease. Med Devices (Auckl). 2014;7:107–14.

    Google Scholar 

  45. Lupsor M et al. Performance of a new elastographic method (arfi technology) compared to unidimensional transient elastography in the noninvasive assessment of chronic hepatitis C. Preliminary Results J Gastrointest Liver Dis. 2009;18(3):303–10.

    Google Scholar 

  46. Takahashi H et al. Evaluation of acoustic radiation force impulse elastography for fibrosis staging of chronic liver disease: a pilot study. Liver Int. 2010;30(4):538–45.

    Article  PubMed  Google Scholar 

  47. Ichikawa S et al. Comparison of the diagnostic accuracies of magnetic resonance elastography and transient elastography for hepatic fibrosis. Magn Reson Imaging. 2015;33(1):26–30.

    Article  PubMed  Google Scholar 

  48. European Association for Study of, L. and H. Asociacion Latinoamericana Para el Estudio del, EASL-ALEH clinical practice guidelines: non-invasive tests for evaluation of liver disease severity and prognosis. J Hepatol. 2015;63(1):237–64.

    Article  Google Scholar 

  49. Castera L et al. Prospective comparison of transient elastography, fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology. 2005;128(2):343–50.

    Article  PubMed  Google Scholar 

  50. de Ledinghen V et al. Diagnosis of hepatic fibrosis and cirrhosis by transient elastography in HIV/hepatitis C virus-coinfected patients. J Acquir Immune Defic Syndr. 2006;41(2):175–9.

    Article  PubMed  Google Scholar 

  51. Vergara S et al. The use of transient elastometry for assessing liver fibrosis in patients with HIV and hepatitis C virus coinfection. Clin Infect Dis. 2007;45(8):969–74.

    Article  PubMed  Google Scholar 

  52. Kirk GD et al. Assessment of liver fibrosis by transient elastography in persons with hepatitis C Virus infection or HIV-hepatitis C virus coinfection. Clin Infect Dis. 2009;48(7):963–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Sanchez-Conde M 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 noninvasive serum markers. J Viral Hepat. 2010;17(4):280–6.

    Article  CAS  PubMed  Google Scholar 

  54. Pineda JA et al. Liver stiffness as a predictor of esophageal varices requiring therapy in HIV/hepatitis C virus-coinfected patients with cirrhosis. J Acquir Immune Defic Syndr. 2009;51(4):445–9.

    Article  PubMed  Google Scholar 

  55. Castera L et al. Comparison of transient elastography (FibroScan), FibroTest, APRI and two algorithms combining these non-invasive tests for liver fibrosis staging in HIV/HCV coinfected patients: ANRS CO13 HEPAVIH and FIBROSTIC collaboration. HIV Med. 2014;15(1):30–9.

    Article  CAS  PubMed  Google Scholar 

  56. Sellier P et al. Description of liver disease in a cohort of HIV/HBV coinfected patients. J Clin Virol. 2010;47(1):13–7.

    Article  CAS  PubMed  Google Scholar 

  57. Hjorth-Hansen H, Waage A, Borset M. Interleukin-15 blocks apoptosis and induces proliferation of the human myeloma cell line OH-2 and freshly isolated myeloma cells. Br J Haematol. 1999;106(1):28–34.

    Article  CAS  PubMed  Google Scholar 

  58. Clinical Practice Guidelines EASL-ALEH. Non-invasive tests for evaluation of liver disease severity and prognosis. J Hepatol. 2015;63(1):237–64.

    Article  Google Scholar 

  59. Bottero J et al. Performance of 11 biomarkers for liver fibrosis assessment in HIV/HBV co-infected patients. J Hepatol. 2009;50(6):1074–83.

    Article  CAS  PubMed  Google Scholar 

  60. Poynard T et al. Overview of the diagnostic value of biochemical markers of liver fibrosis (FibroTest, HCV FibroSure) and necrosis (ActiTest) in patients with chronic hepatitis C. Comp Hepatol. 2004;3(1):8.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Sporea I et al. Liver stiffness measurements in patients with HBV vs HCV chronic hepatitis: a comparative study. World J Gastroenterol. 2010;16(38):4832–7.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Cardoso AC et al. Direct comparison of diagnostic performance of transient elastography in patients with chronic hepatitis B and chronic hepatitis C. Liver Int. 2012;32(4):612–21.

    Article  CAS  PubMed  Google Scholar 

  63. Miailhes P et al. Proficiency of transient elastography compared to liver biopsy for the assessment of fibrosis in HIV/HBV-coinfected patients. J Viral Hepat. 2011;18(1):61–9.

    Article  CAS  PubMed  Google Scholar 

  64. Crum-Cianflone N et al. Nonalcoholic fatty liver disease among HIV-infected persons. J Acquir Immune Defic Syndr. 2009;50(5):464–73.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Ingiliz P et al. Liver damage underlying unexplained transaminase elevation in human immunodeficiency virus-1 mono-infected patients on antiretroviral therapy. Hepatology. 2009;49(2):436–42.

    Article  PubMed  Google Scholar 

  66. Price JC et al. Risk factors for fatty liver in the multicenter AIDS cohort study. Am J Gastroenterol. 2014;109(5):695–704.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Grunfeld C. Insulin resistance in HIV infection: drugs, host responses, or restoration to health? Top HIV Med. 2008;16(2):89–93.

    PubMed  Google Scholar 

  68. Carr A et al. A syndrome of lipoatrophy, lactic acidaemia and liver dysfunction associated with HIV nucleoside analogue therapy: contribution to protease inhibitor-related lipodystrophy syndrome. AIDS. 2000;14(3):F25–32.

    Article  CAS  PubMed  Google Scholar 

  69. Shah AG et al. Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2009;7(10):1104–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. McPherson S et al. Simple non-invasive fibrosis scoring systems can reliably exclude advanced fibrosis in patients with non-alcoholic fatty liver disease. Gut. 2010;59(9):1265–9.

    Article  PubMed  Google Scholar 

  71. Wong VW et al. Validation of the NAFLD fibrosis score in a Chinese population with low prevalence of advanced fibrosis. Am J Gastroenterol. 2008;103(7):1682–8.

    PubMed  Google Scholar 

  72. Morse CG 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.

    PubMed  PubMed Central  Google Scholar 

  73. Wong VW et al. Liver stiffness measurement using XL probe in patients with nonalcoholic fatty liver disease. Am J Gastroenterol. 2012;107(12):1862–71.

    Article  PubMed  Google Scholar 

  74. Wong VW et al. Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease. Hepatology. 2010;51(2):454–62.

    Article  CAS  PubMed  Google Scholar 

  75. Yoneda M et al. Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with nonalcoholic fatty liver disease (NAFLD). Dig Liver Dis. 2008;40(5):371–8.

    Article  CAS  PubMed  Google Scholar 

  76. Lupsor M et al. Performance of unidimensional transient elastography in staging non-alcoholic steatohepatitis. J Gastrointestin Liver Dis. 2010;19(1):53–60.

    PubMed  Google Scholar 

  77. Bureau C et al. Transient elastography accurately predicts presence of significant portal hypertension in patients with chronic liver disease. Aliment Pharmacol Ther. 2008;27(12):1261–8.

    Article  CAS  PubMed  Google Scholar 

  78. Lemoine M et al. Liver stiffness measurement as a predictive tool of clinically significant portal hypertension in patients with compensated hepatitis C virus or alcohol-related cirrhosis. Aliment Pharmacol Ther. 2008;28(9):1102–10.

    Article  CAS  PubMed  Google Scholar 

  79. Shi KQ et al. Transient elastography: a meta-analysis of diagnostic accuracy in evaluation of portal hypertension in chronic liver disease. Liver Int. 2013;33(1):62–71.

    Article  PubMed  Google Scholar 

  80. Vizzutti F et al. Liver stiffness measurement predicts severe portal hypertension in patients with hcv-related cirrhosis. Hepatology. 2007;45(5):1290–7.

    Article  PubMed  Google Scholar 

  81. Colecchia A et al. Measurement of spleen stiffness to evaluate portal hypertension and the presence of esophageal varices in patients with HCV-related cirrhosis. Gastroenterology. 2012;143(3):646–54.

    Article  PubMed  Google Scholar 

  82. Masuzaki R et al. Prospective risk assessment for hepatocellular carcinoma development in patients with chronic hepatitis C by transient elastography. Hepatology. 2009;49(6):1954–61.

    Article  PubMed  Google Scholar 

  83. Jung KS et al. Risk assessment of hepatitis B virus-related hepatocellular carcinoma development using liver stiffness measurement (FibroScan). Hepatology. 2011;53(3):885–94.

    Article  CAS  PubMed  Google Scholar 

  84. Robic MA et al. Liver stiffness accurately predicts portal hypertension related complications in patients with chronic liver disease: a prospective study. J Hepatol. 2011;55(5):1017–24.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine, Duke University Medical Center, Durham, NC, USA

    Bassem Matta

  2. Division of General Internal Medicine, Koo Foundation Sun Yat-Sen Cancer Center, Taipei City, Taiwan

    Tzu-Hao Lee

  3. Toronto Centre for Liver Disease, University Health Network Toronto, Toronto, ON, Canada

    Keyur Patel

  4. University of Toronto, Toronto Centre for Liver Disease, Toronto General Hospital, Eaton North, 9th floor Room 232, 200 Elizabeth Street, Toronto, ON, M5G 2C4, Canada

    Keyur Patel

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  1. Bassem Matta
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  2. Tzu-Hao Lee
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  3. Keyur Patel
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Correspondence to Keyur Patel.

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Bassem Matta, Tzu-Hao Lee, and Keyur Patel declare that they have no conflict of interest.

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This article is part of the Topical Collection on Co-infections and Comorbidity

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Matta, B., Lee, TH. & Patel, K. Use of Non-invasive Testing to Stage Liver Fibrosis in Patients with HIV. Curr HIV/AIDS Rep 13, 279–288 (2016). https://doi.org/10.1007/s11904-016-0329-5

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