Document Type : Review Article


1 Department of Clinical Biochemistry, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran

2 Department of Molecular Medicine, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran

3 Biopharmaceutical Research Center, AryoGen Pharmed Inc, Alborz University of Medical Sciences, Karaj, Iran


Recently, prevalence of hepatitis B virus (HBV), and hepatitis C virus (HCV) co-infection with Human immunodeficiency virus (HIV), has dramatically increased worldwide due to their shared routes of transmission. Compared to sporadic infection with HIV, HBV, and HCV, concurrent infection with these agents increases the effects and complications of these viruses. Furthermore, co-infection may also alter therapeutic strategies against HIV. Accordingly, choosing appropriate biomarkers to detect these co -infections is one of the main concerns in the field of diagnostic pathology. Up to now, several markers have been introduced for simultaneous diagnosis of HIV, HBV, and HCV. In this regard, serum adenosine deaminase activity (ADA), Fibro Tests, AST-to-Platelet Ratio Index (APRI), Fibrosis-4, Hyaluronic acid, and micro ribonucleic acids have been investigated as potential biomarkers for diagnosis of HIV-HCV/HBV co-infections. This work summarizes the diagnostic value of current and emerging biomarkers in HIV patients concurrently infected with HBV and HCV.


Main Subjects

  1. Pham QD, Wilson DP, Law MG, Kelleher AD, Zhang L. Global burden of transmitted HIV drug resistance and HIV-exposure categories: a systematic review and meta-analysis. AIDS. 2014;28(18):2751-62. [DOI:10.1097/QAD.0000000000000494] [PMID]
  2. Stabinski L, O'Connor S, Barnhart M, Kahn RJ, Hamm TE. Prevalence of HIV and hepatitis B virus co-infection in sub-Saharan Africa and the potential impact and program feasibility of hepatitis B surface antigen screening in resource-limited settings. J Acquir Immune Defic Syndr. 2015;68 Suppl 3:S274-85. [DOI:10.1097/QAI.0000000000000496] [PMID]
  3. Fettig J, Swaminathan M, Murrill CS, Kaplan JE. Global epidemiology of HIV. Infect Dis Clin North Am. 2014;28(3):323-37. [DOI:10.1016/j.idc.2014.05.001] [PMID] [PMCID]
  4. Seitz R. Human Immunodeficiency Virus (HIV). Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfus Immunhamatol. 2016;43(3):203-22
  5. Hladik F, McElrath MJ. Setting the stage: host invasion by HIV. Nat Rev Immunol. 2008;8(6):447-57. [DOI:10.1038/nri2302] [PMID] [PMCID]
  6. Sharp PM, Hahn BH. Origins of HIV and the AIDS pandemic. Cold Spring Harb Perspect Med. 2011;1(1):a006841. [DOI:10.1101/cshperspect.a006841] [PMID] [PMCID]
  7. Bartolo I, Rocha C, Bartolomeu J, Gama A, Marcelino R, Fonseca M, et al. Highly divergent subtypes and new recombinant forms prevail in the HIV/AIDS epidemic in Angola: new insights into the origins of the AIDS pandemic. Infect Genet Evol. 2009;9(4):672-82. [DOI:10.1016/j.meegid.2008.05.003] [PMID]
  8. Alter MJ. Epidemiology of viral hepatitis and HIV co-infection. Journal of hepatology. 2006;44(1 Suppl):S6-9. [DOI:10.1016/j.jhep.2005.11.004] [PMID]
  9. Diop-Ndiaye H, Toure-Kane C, Etard JF, Lo G, Diaw P, Ngom-Gueye NF, et al. Hepatitis B, C seroprevalence and delta viruses in HIV-1 Senegalese patients at HAART initiation (retrospective study). J Med Virol. 2008;80(8):1332-6. [DOI:10.1002/jmv.21236] [PMID]
  10. Hosseini M, SeyedAlinaghi S, Kheirandish P, Esmaeli Javid G, Shirzad H, Karami N, et al. Prevalence and correlates of co-infection with human immunodeficiency virus and hepatitis C virus in male injection drug users in Iran. Arch Iran Med. 2010;13(4):318-23.
  11. Moradi A, Khodabakhshi B, Sadeghipour M, Besharat S, Tabarraei A. Concurrent infections of hepatitis C and HIV in hepatitis B patients in the north-east of Iran. Tropic Doctor. 2011;41(3):129-31. [DOI:10.1258/td.2011.100418] [PMID]
  12. Tyson GL, Kramer JR, Duan Z, Davila JA, Richardson PA, El-Serag HB. Prevalence and predictors of hepatitis B virus coinfection in a United States cohort of hepatitis C virus-infected patients. Hepatology (Baltimore, Md. 2013;58(2):538-45. [DOI:10.1002/hep.26400] [PMID] [PMCID]
  13. Agutu CA, Ngetsa CJ, Price MA, Rinke de Wit TF, Omosa-Manyonyi G, Sanders EJ, et al. Systematic review of the performance and clinical utility of point of care HIV-1 RNA testing for diagnosis and care. PLoS One. 2019;14(6):e0218369. [DOI:10.1371/journal.pone.0218369] [PMID] [PMCID]
  14. Marinho FLO, Santos NLL, Neves SPF, Vasconcellos LS. Performance evaluation of eight rapid tests to detect HIV infection: A comparative study from Brazil. PLoS One. 2020;15(8):e0237438. [DOI:10.1371/journal.pone.0237438] [PMID] [PMCID]
  15. Mourez T, Lemee V, Delbos V, Delaugerre C, Alessandri-Gradt E, Etienne M, et al. HIV rapid screening tests and self-tests: Be aware of differences in performance and cautious of vendors. EBioMedicine. 2018;37:382-91. [DOI:10.1016/j.ebiom.2018.10.012] [PMID] [PMCID]
  16. Guarner J. Human immunodeficiency virus: Diagnostic approach. Semin Diagn Pathol. 2017;34(4):318-24
  17. Simon V, Ho DD, Abdool Karim Q. HIV/AIDS epidemiology, pathogenesis, prevention, and treatment. Lancet. 2006;368(9534):489-504. [DOI:10.1016/S0140-6736(06)69157-5] [PMID]
  18. Grossman Z, Kra-Oz Z. [HIV testing: the medical laboratory role in HIV diagnosis and monitoring]. Harefuah. 2013;152(8):477-80, 98.
  19. World Health O. WHO recommends countries move away from the use of western blotting and line immunoassays in HIV testing strategies and algorithms: policy brief. Geneva: World Health Organization; 2019 2019. Contract No.: WHO/CDS/HIV/19.30.
  20. Branson BM, Owen SM, Wesolowski LG, Bennett B, Werner BG, Wroblewski KE, et al. Laboratory testing for the diagnosis of HIV infection : updated recommendations. In: Centers for Disease C, Prevention, Association of Public Health L, National Center for Hiv/Aids VH, Prevention TBPDoHA, editors. Atlanta, GA.2014. [DOI: 15620/cdc.23447]
  21. Nunez M, Puoti M, Camino N, Soriano V. Treatment of chronic hepatitis B in the human immunodeficiency virus-infected patient: present and future. Clin Infect Dis. 2003;37(12):1678-85. [DOI:10.1086/379774] [PMID]
  22. Schiavini M, Angeli E, Mainini A, Uberti-Foppa C, Zerbi P, Sagnelli C, et al. Fibrosis progression in paired liver biopsies from HIV/HCV co-infected patients. Hepatitis Monthly. 2011;11(7):525-31.
  23. Thio CL, Seaberg EC, Skolasky R, Jr., Phair J, Visscher B, Munoz A, 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. [DOI:10.1016/S0140-6736(02)11913-1] [PMID]
  24. Niedzwicki JG, Kouttab NM, Mayer KH, Carpenter CC, Parks RE, Jr., Abushanab E, et al. Plasma adenosine deaminase2: a marker for human immunodeficiency virus infection. J Acquir Immune Defic Syndr (1988). 1991;4(2):178-82.
  25. Chittiprol S, P S, S BR, R RG, V SS, K SD, et al. Plasma adenosine deaminase activity among HIV1 Clade C seropositives: Relation to CD4 T cell population and antiretroviral therapy. Clin Chim Act. 2007;377:133-7. [DOI:10.1016/j.cca.2006.09.006] [PMID]
  26. Kaya S, Cetin ES, Aridogan BC, Arikan S, Demirci M. Adenosine deaminase activity in serum of patients with hepatitis -- a useful tool in monitoring clinical status. J Microbiol Immunol Infect. 2007;40(4):288-92.
  27. Phillis J. Adenosine and adenine nuleotides as regulators of cellular function: CRC Press; 1991. 71-85 p.
  28. Conway EJ, Cooke R. The deaminases of adenosine and adenylic acid in blood and tissues. The Biochemical journal. 1939;33(4):479-92. [DOI:10.1042/bj0330479] [PMID] [PMCID]
  29. Van der Weyden MB, Kelley WN. Human adenosine deaminase. Distribution and properties. J Biol Chem. 1976;251(18):5448-56. [DOI:10.1016/S0021-9258(17)33080-6]
  30. Gakis C. Adenosine deaminase (ADA) isoenzymes ADA1 and ADA2: diagnostic and biological role. Eur Respir J. 1996;9(4):632-3. [DOI:10.1183/09031936.96.09040632] [PMID]
  31. Zidek Z. Adenosine - cyclic AMP pathways and cytokine expression. Eur Cytokine Netw. 1999;10(3):319-28.
  32. Goodarzi MT, Abdi M, Tavilani H, Nadi E, Rashidi M. Adenosine deaminase activity in COPD patients and healthy subjects. Iranian journal of allergy, asthma, and immunology. 2010;9(1):7-12.
  33. Khodadadi I, Vahedi MS, Abdi M, Daneshkhah N, Rahbari R, Menbari S, et al. Evaluation of adenosine deaminase (ADA) isoenzymes activity and tumor necrosis factor-alpha (TNFalpha) concentration in chronic heart failure. EXCLI J. 2014;13:58-66.
  34. Ungerer JP, Oosthuizen HM, Bissbort SH, Vermaak WJ. Serum adenosine deaminase: isoenzymes and diagnostic application. Clin Chem. 1992;38(7):1322-6. [DOI:10.1093/clinchem/38.7.1322] [PMID]
  35. Kalkan A, Bulut V, Erel O, Avci S, Bingol NK. Adenosine deaminase and guanosine deaminase activities in sera of patients with viral hepatitis. Memorias Institut Oswaldo Cruz. 1999;94(3):383-6. [DOI:10.1590/S0074-02761999000300018] [PMID]
  36. Tsuboi I, Sagawa K, Shichijo S, Yokoyama MM, Ou DW, Wiederhold MD. Adenosine deaminase isoenzyme levels in patients with human T-cell lymphotropic virus type 1 and human immunodeficiency virus type 1 infections. Clin Diagn Lab Immunol. 1995;2(5):626-30. [DOI:10.1128/cdli.2.5.626-630.1995] [PMID] [PMCID]
  37. Abdi M, Ahmadi A, Roshany D, Khodadadi I, Javid S, Shahmohammad-Nezhad S, et al. Diagnostic value of serum adenosine deaminase activity in HIV infected patients of Kurdish population. Clin Lab. 2013;59(7-8):757-62. [DOI:10.7754/Clin.Lab.2012.120631] [PMID]
  38. Khodadadi I, Abdi M, Ahmadi A, Wahedi MS, Menbari S, Lahoorpour F, et al. Analysis of serum adenosine deaminase (ADA) and ADA1 and ADA2 isoenzyme activities in HIV positive and HIV-HBV co-infected patients. Clin Biochem. 2011;44(12):980-3. [DOI:10.1016/j.clinbiochem.2011.05.020] [PMID]
  39. Abdi M, Rahbari R, Khatooni Z, Naseri N, Najafi A, Khodadadi I. Serum Adenosine Deaminase (ADA) Activity: A Novel Screening Test to Differentiate HIV Monoinfection From HIV-HBV and HIV-HCV Coinfections. J Clin Lab Anal. 2016;30(3):200-3. [DOI:10.1002/jcla.21836] [PMID] [PMCID]
  40. Myers RP, Tainturier MH, Ratziu V, Piton A, Thibault V, Imbert-Bismut F, et al. Prediction of liver histological lesions with biochemical markers in patients with chronic hepatitis B. J Hepatol. 2003;39(2):222-30. [DOI:10.1016/S0168-8278(03)00171-5] [PMID]
  41. Myers RP, Benhamou Y, Imbert-Bismut F, Thibault V, Bochet M, Charlotte F, et al. Serum biochemical markers accurately predict liver fibrosis in HIV and hepatitis C virus co-infected patients. AIDS. 2003;17(5):721-5. [DOI:10.1097/00002030-200303280-00010] [PMID]
  42. Vermehren J, Vermehren A, Mueller A, Carlebach A, Lutz T, Gute P, et al. Assessment of liver fibrosis and associated risk factors in HIV-infected individuals using transient elastography and serum biomarkers. BMC Gastroenterol. 2012;12:27. [DOI:10.1186/1471-230X-12-27] [PMID] [PMCID]
  43. Wondimeneh Y, Alem M, Asfaw F, Belyhun Y. HBV and HCV seroprevalence and their correlation with CD4 cells and liver enzymes among HIV positive individuals at University of Gondar Teaching Hospital, Northwest Ethiopia. Virol J. 2013;10:171. [DOI:10.1186/1743-422X-10-171] [PMID] [PMCID]
  44. Lodenyo H, Schoub B, Ally R, Kairu S, Segal I. Hepatitis B and C virus infections and liver function in AIDS patients at Chris Hani Baragwanath Hospital, Johannesburg. East Afr Med J. 2000;77(1):13-5. [DOI:10.4314/eamj.v77i1.46369] [PMID]
  45. Tripathi AK, Khanna M, Gupta N, Chandra M. Low prevalence of hepatitis B virus and hepatitis C virus co-infection in patients with human immunodeficiency virus in Northern India. J Assoc Physicians India. 2007;55:429-31.
  46. Mata-Marin JA, Gaytan-Martinez J, Grados-Chavarria BH, Fuentes-Allen JL, Arroyo-Anduiza CI, Alfaro-Mejia A. Correlation between HIV viral load and aminotransferases as liver damage markers in HIV infected naive patients: a concordance cross-sectional study. Virol J. 2009;6:181. [DOI:10.1186/1743-422X-6-181] [PMID] [PMCID]
  47. Cao YZ, Dieterich D, Thomas PA, Huang YX, Mirabile M, Ho DD. Identification and quantitation of HIV-1 in the liver of patients with AIDS. AIDS. 1992;6(1):65-70. [DOI:10.1097/00002030-199201000-00008] [PMID]
  48. Hooja S, Singhal A, Bachhiwal R, Yadav R, Vyas N. Hepatitis B virus seroprevalence and its correlation with CD4 cells and liver enzymes among human immunodeficiency virus positive individuals at a tertiary care hospital in North-West India. Int J Appl Basic Med Res. 2015;5(1):36-40. [DOI:10.4103/2229-516X.149235] [PMID] [PMCID]
  49. ter Borg F, ten Kate FJ, Cuypers HT, Leentvaar-Kuijpers A, Oosting J, Wertheim-van Dillen PM, et al. Relation between laboratory test results and histological hepatitis activity in individuals positive for hepatitis B surface antigen and antibodies to hepatitis B e antigen. Lancet. 1998;351(9120):1914-8. [DOI:10.1016/S0140-6736(97)09391-4] [PMID]
  50. Adewole OO, Anteyi E, Ajuwon Z, Wada I, Elegba F, Ahmed P, et al. Hepatitis B and C virus co-infection in Nigerian patients with HIV infection. J Infect Dev Ctries. 2009;3(5):369-75. [DOI:10.3855/jidc.245] [PMID]
  51. Leierer G, Rieger A, Schmied B, Sarcletti M, Ollinger A, Wallner E, et al. A Lower CD4 Count Predicts Most Causes of Death except Cardiovascular Deaths. The Austrian HIV Cohort Study. Int J Environ Res Public Health. 2021;18(23). [DOI:10.3390/ijerph182312532] [PMID] [PMCID]
  52. Milic J, Menozzi V, Schepis F, Malagoli A, Besutti G, Franconi I, et al. Liver steatosis and nonalcoholic fatty liver disease with fibrosis are predictors of frailty in people living with HIV. AIDS. 2020;34(13):1915-21. [DOI:10.1097/QAD.0000000000002650] [PMID]
  53. Perazzo H, Cardoso SW, Yanavich C, Nunes EP, Morata M, Gorni N, 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):e25201. [DOI:10.1002/jia2.25201] [PMID] [PMCID]
  54. Organization WH. Guidelines for the screening, care and treatment of persons with hepatitis C infection: World health organization; 2014.
  55. Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS, et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology (Baltimore, Md. 2003;38(2):518-26. [DOI:10.1053/jhep.2003.50346] [PMID]
  56. DallaPiazza M, Amorosa VK, Localio R, Kostman JR, Lo Re V, 3rd. Prevalence and risk factors for significant liver fibrosis among HIV-monoinfected patients. BMC Infect Dis. 2010;10:116. [DOI:10.1186/1471-2334-10-116] [PMID] [PMCID]
  57. Kelleher TB, Mehta SH, Bhaskar R, Sulkowski M, Astemborski J, Thomas DL, 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. [DOI:10.1016/j.jhep.2005.02.025] [PMID]
  58. Moodie EE, Pant Pai N, Klein MB. Is antiretroviral therapy causing long-term liver damage? A comparative analysis of HIV-mono-infected and HIV/hepatitis C co-infected cohorts. PLoS One. 2009;4(2):e4517. [DOI:10.1371/journal.pone.0004517] [PMID] [PMCID]
  59. Mohamadnejad M, Montazeri G, Fazlollahi A, Zamani F, Nasiri J, Nobakht H, et al. Noninvasive markers of liver fibrosis and inflammation in chronic hepatitis B-virus related liver disease. Am J Gastroenterol. 2006;101(11):2537-45. [DOI:10.1111/j.1572-0241.2006.00788.x] [PMID]
  60. Poynard T, Zoulim F, Ratziu V, Degos F, Imbert-Bismut F, Deny P, et al. Longitudinal assessment of histology surrogate markers (FibroTest-ActiTest) during lamivudine therapy in patients with chronic hepatitis B infection. Am J Gastroenterol. 2005;100(9):1970-80. [DOI:10.1111/j.1572-0241.2005.41957.x] [PMID]
  61. Imbert-Bismut F, Ratziu V, Pieroni L, Charlotte F, Benhamou Y, Poynard T, et al. Biochemical markers of liver fibrosis in patients with hepatitis C virus infection: a prospective study. Lancet. 2001;357(9262):1069-75. [DOI:10.1016/S0140-6736(00)04258-6] [PMID]
  62. Poynard T, Imbert-Bismut F, Munteanu M, Messous D, Myers RP, Thabut D, 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. [DOI:10.1186/1476-5926-3-8] [PMID] [PMCID]
  63. Kawser CA, Iredale JP, Winwood PJ, Arthur MJ. Rat hepatic stellate cell expression of alpha2-macroglobulin is a feature of cellular activation: implications for matrix remodelling in hepatic fibrosis. Clin Sci (Lond). 1998;95(2):179-86. [DOI:10.1042/cs0950179] [PMID]
  64. Sumida Y, Nakajima A, Itoh 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(2):475-85. [DOI:10.3748/wjg.v20.i2.475] [PMID] [PMCID]
  65. Sterling RK, Lissen E, Clumeck N, Sola R, Correa MC, Montaner J, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology (Baltimore, Md. 2006;43(6):1317-25. [DOI:10.1002/hep.21178] [PMID]
  66. Castera L, Vergniol J, Foucher J, Le Bail B, Chanteloup E, Haaser M, 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. [DOI:10.1053/j.gastro.2004.11.018] [PMID]
  67. Resino S, Sanchez-Conde M, Berenguer J. Coinfection by human immunodeficiency virus and hepatitis C virus: noninvasive assessment and staging of fibrosis. Curr Opin Infect Dis. 2012;25(5):564-9. [DOI:10.1097/QCO.0b013e32835635df] [PMID]
  68. Xu XY, Kong H, Song RX, Zhai YH, Wu XF, Ai WS, et al. The effectiveness of noninvasive biomarkers to predict hepatitis B-related significant fibrosis and cirrhosis: a systematic review and meta-analysis of diagnostic test accuracy. PLoS One. 2014;9(6):e100182. [DOI:10.1371/journal.pone.0100182] [PMID] [PMCID]
  69. Vallet-Pichard A, Mallet V, Nalpas B, Verkarre V, Nalpas A, Dhalluin-Venier V, et al. FIB-4: an inexpensive and accurate marker of fibrosis in HCV infection. comparison with liver biopsy and fibrotest. Hepatology (Baltimore, Md. 2007;46(1):32-6. [DOI:10.1002/hep.21669] [PMID]
  70. Gower E, Estes C, Blach S, Razavi-Shearer K, Razavi H. Global epidemiology and genotype distribution of the hepatitis C virus infection. Journal of hepatology. 2014;61(1 Suppl):S45-57. [DOI:10.1016/j.jhep.2014.07.027] [PMID]
  71. Sunbul M. Hepatitis B virus genotypes: global distribution and clinical importance. World J Gastroenterol. 2014;20(18):5427-34. [DOI:10.3748/wjg.v20.i18.5427] [PMID] [PMCID]
  72. 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 (Baltimore, Md. 2007;46(3):912-21. [DOI:10.1002/hep.21835] [PMID]
  73. Vinikoor MJ, Sinkala E, Mweemba A, Zanolini A, Mulenga L, Sikazwe I, et al. Elevated AST-to-platelet ratio index is associated with increased all-cause mortality among HIV-infected adults in Zambia. Liver Int. 2015;35(7):1886-92. [DOI:10.1111/liv.12780] [PMID] [PMCID]
  74. Halfon P, Bacq Y, De Muret A, Penaranda G, Bourliere M, Ouzan D, et al. Comparison of test performance profile for blood tests of liver fibrosis in chronic hepatitis C. J Hepatol. 2007;46(3):395-402. [DOI:10.1016/j.jhep.2006.09.020] [PMID]
  75. Passos AM, Treitinger A, Spada C. An overview of the mechanisms of HIV-related thrombocytopenia. Acta Haematol. 2010;124(1):13-8. [DOI:10.1159/000313782] [PMID]
  76. Hull MW, Rollet K, Odueyungbo A, Saeed S, Potter M, Cox J, et al. Factors associated with discordance between absolute CD4 cell count and CD4 cell percentage in patients coinfected with HIV and hepatitis C virus. Clin Infect Dis. 2012;54(12):1798-805. [DOI:10.1093/cid/cis289] [PMID]
  77. Price JC, Seaberg EC, Badri S, Witt MD, D'Acunto K, Thio CL. HIV monoinfection is associated with increased aspartate aminotransferase-to-platelet ratio index, a surrogate marker for hepatic fibrosis. J Infect Dis. 2012;205(6):1005-13. [DOI:10.1093/infdis/jir885] [PMID] [PMCID]
  78. Mendeni M, Foca E, Gotti D, Ladisa N, Angarano G, Albini L, et al. Evaluation of liver fibrosis: concordance analysis between noninvasive 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(9):1164-73. [DOI:10.1093/cid/cir071] [PMID]
  79. Singal AG, Thomassen LV, Gretch DR, Shuhart MC. Use of the AST to platelet ratio index in HCV/HIV co-infected patients. Aliment Pharmacol Ther. 2011;33(5):566-77. [DOI:10.1111/j.1365-2036.2010.04560.x] [PMID] [PMCID]
  80. Macias J, Giron-Gonzalez JA, Gonzalez-Serrano M, Merino D, Cano P, Mira JA, 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. [DOI:10.1136/gut.2005.065904] [PMID] [PMCID]
  81. Smith JO, Sterling RK. Systematic review: non-invasive methods of fibrosis analysis in chronic hepatitis C. Aliment Pharmacol Ther. 2009;30(6):557-76. [DOI:10.1111/j.1365-2036.2009.04062.x] [PMID]
  82. Blau N, Duran M, Gibson K. Laboratory Guide to the Methods in Biochemical Genetics. pp287-324. First edition ed: Springer-Verlag Berlin Heidelberg; 2008. [DOI:10.1007/978-3-540-76698-8]
  83. Salbach J, Rachner TD, Rauner M, Hempel U, Anderegg U, Franz S, et al. Regenerative potential of glycosaminoglycans for skin and bone. J Molecul Med (Berlin, Germany). 2012;90(6):625-35. [DOI:10.1007/s00109-011-0843-2] [PMID]
  84. Gressner OA, Weiskirchen R, Gressner AM. Biomarkers of liver fibrosis: clinical translation of molecular pathogenesis or based on liver-dependent malfunction tests. Int J Clin Chem. 2007;381(2):107-13. [DOI:10.1016/j.cca.2007.02.038] [PMID]
  85. Montazeri G, Estakhri A, Mohamadnejad M, Nouri N, Montazeri F, Mohammadkani A, et al. Serum hyaluronate as a non-invasive marker of hepatic fibrosis and inflammation in HBeAg-negative chronic hepatitis B. BMC Gastroenterol. 2005;5:32. [DOI:10.1186/1471-230X-5-32] [PMID] [PMCID]
  86. Parsian H, Rahimipour A, Nouri M, Somi MH, Qujeq D. Assessment of liver fibrosis development in chronic hepatitis B patients by serum hyaluronic acid and laminin levels. Acta Clin Croatica. 2010;49(3):257-65.
  87. Zhang YX, Wu WJ, Zhang YZ, Feng YL, Zhou XX, Pan Q. Noninvasive assessment of liver fibrosis with combined serum aminotransferase/platelet ratio index and hyaluronic acid in patients with chronic hepatitis B. World J Gastroenterol. 2008;14(46):7117-21. [DOI:10.3748/wjg.14.7117] [PMID] [PMCID]
  88. Arain SA, Meo SA, Jamal Q. Serum hyaluronic acid level does not reliably differentiate minimal and significant liver disease in chronic hepatitis C. Saudi Med J. 2011;32(12):1241-5.
  89. Patel K, Lajoie A, Heaton S, Pianko S, Behling CA, Bylund D, et al. Clinical use of hyaluronic acid as a predictor of fibrosis change in hepatitis C. J Gastroenterol Hepatol. 2003;18(3):253-7. [DOI:10.1046/j.1440-1746.2003.02930.x] [PMID]
  90. Peters L, Mocroft A, Soriano V, Rockstroh J, Rauch A, Karlsson A, et al. Hyaluronic acid levels predict risk of hepatic encephalopathy and liver-related death in HIV/viral hepatitis coinfected patients. PLoS One. 2013;8(5):e64283. [DOI:10.1371/journal.pone.0064283] [PMID] [PMCID]
  91. Rostami S, Parsian H. Hyaluronic Acid: from biochemical characteristics to its clinical translation in assessment of liver fibrosis. Hepatitis Monthly. 2013;13(12):e13787. [DOI:10.5812/hepatmon.13787]
  92. Hakim ST, Alsayari M, McLean DC, Saleem S, Addanki KC, Aggarwal M, et al. A large number of the human microRNAs target lentiviruses, retroviruses, and endogenous retroviruses. Biochem Biophysic Res Commun. 2008;369(2):357-62. [DOI:10.1016/j.bbrc.2008.02.025] [PMID]
  93. Houzet L, Jeang KT. MicroRNAs and human retroviruses. Biochim Biophysic Acta. 2011;1809(11-12):686-93. [DOI:10.1016/j.bbagrm.2011.05.009] [PMID] [PMCID]
  94. Egana-Gorrono L, Escriba T, Boulanger N, Guardo AC, Leon A, Bargallo ME, et al. Differential microRNA expression profile between stimulated PBMCs from HIV-1 infected elite controllers and viremic progressors. PLoS One. 2014;9(9):e106360. [DOI:10.1371/journal.pone.0106360] [PMID] [PMCID]
  95. Skalsky RL, Cullen BR. Viruses, microRNAs, and host interactions. Annual Rev Microbiol. 2010;64:123-41. [DOI:10.1146/annurev.micro.112408.134243] [PMID] [PMCID]
  96. Jopling CL, Yi M, Lancaster AM, Lemon SM, Sarnow P. Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science (New York, NY. 2005;309(5740):1577-81. [DOI:10.1126/science.1113329] [PMID]
  97. Zhu Z, Wilson AT, Mathahs MM, Wen F, Brown KE, Luxon BA, et al. Heme oxygenase-1 suppresses hepatitis C virus replication and increases resistance of hepatocytes to oxidant injury. Hepatology (Baltimore, Md. 2008;48(5):1430-9. [DOI:10.1002/hep.22491] [PMID] [PMCID]
  98. Bihrer V, Waidmann O, Friedrich-Rust M, Forestier N, Susser S, Haupenthal J, et al. Serum microRNA-21 as marker for necroinflammation in hepatitis C patients with and without hepatocellular carcinoma. PLoS One. 2011;6(10):e26971. [DOI:10.1371/journal.pone.0026971] [PMID] [PMCID]
  99. Chen Y, Chen J, Wang H, Shi J, Wu K, Liu S, et al. HCV-induced miR-21 contributes to evasion of host immune system by targeting MyD88 and IRAK1. PLoS Pathog. 2013;9(4):e1003248. [DOI:10.1371/journal.ppat.1003248] [PMID] [PMCID]
  100. Zeitels LR, Acharya A, Shi G, Chivukula D, Chivukula RR, Anandam JL, et al. Tumor suppression by miR-26 overrides potential oncogenic activity in intestinal tumorigenesis. Gen Dev. 2014;28(23):2585-90. [DOI:10.1101/gad.250951.114] [PMID] [PMCID]
  101. Jangra RK, Yi M, Lemon SM. Regulation of hepatitis C virus translation and infectious virus production by the microRNA miR-122. J Virol. 2010;84(13):6615-25. [DOI:10.1128/JVI.00417-10] [PMID] [PMCID]
  102. Xing TJ, Jiang DF, Huang JX, Xu ZL. Expression and clinical significance of miR-122 and miR-29 in hepatitis B virus-related liver disease. Genet Mol Res. 2014;13(3):7912-8. [DOI:10.4238/2014.September.29.4] [PMID]
  103. Cheng HR, Kao JH, Wu HL, Tseng TC, Liu CH, Yang HC, et al. Clinical significance of circulating miR-122 in patients with dual chronic hepatitis B and C virus infection. Hepatol Int. 2015;9(1):35-42. [DOI:10.1007/s12072-014-9591-z] [PMID]
  104. Song K, Han C, Dash S, Balart LA, Wu T. MiR-122 in hepatitis B virus and hepatitis C virus dual infection. World J Hepatol. 2015;7(3):498-506. [DOI:10.4254/wjh.v7.i3.498] [PMID] [PMCID]
  105. Gupta A, Swaminathan G, Martin-Garcia J, Navas-Martin S. MicroRNAs, hepatitis C virus, and HCV/HIV-1 co-infection: new insights in pathogenesis and therapy. Viruses. 2012;4(11):2485-513. [DOI:10.3390/v4112485] [PMID] [PMCID]
  106. Triboulet R, Mari B, Lin YL, Chable-Bessia C, Bennasser Y, Lebrigand K, et al. Suppression of microRNA-silencing pathway by HIV-1 during virus replication. Science (New York, NY. 2007;315(5818):1579-82. [DOI:10.1126/science.1136319] [PMID]
  107. Manfe V, Biskup E, Rosbjerg A, Kamstrup M, Skov AG, Lerche CM, et al. miR-122 regulates p53/Akt signalling and the chemotherapy-induced apoptosis in cutaneous T-cell lymphoma. PLoS One. 2012;7(1):e29541. [DOI:10.1371/journal.pone.0029541] [PMID] [PMCID]
  108. Bandyopadhyay S, Friedman RC, Marquez RT, Keck K, Kong B, Icardi MS, et al. Hepatitis C virus infection and hepatic stellate cell activation downregulate miR-29: miR-29 overexpression reduces hepatitis C viral abundance in culture. J Infect Dis. 2011;203(12):1753-62. [DOI:10.1093/infdis/jir186] [PMID] [PMCID]
  109. Nathans R, Chu CY, Serquina AK, Lu CC, Cao H, Rana TM. Cellular microRNA and P bodies modulate host-HIV-1 interactions. Molecul cell. 2009;34(6):696-709. [DOI:10.1016/j.molcel.2009.06.003] [PMID] [PMCID]
  110. Wang X, Ye L, Hou W, Zhou Y, Wang YJ, Metzger DS, et al. Cellular microRNA expression correlates with susceptibility of monocytes/macrophages to HIV-1 infection. Blood. 2009;113(3):671-4. [DOI:10.1182/blood-2008-09-175000] [PMID] [PMCID]
  111. Xu J, Wu C, Che X, Wang L, Yu D, Zhang T, et al. Circulating microRNAs, miR-21, miR-122, and miR-223, in patients with hepatocellular carcinoma or chronic hepatitis. Molecul Carcinogen. 2011;50(2):136-42. [DOI:10.1002/mc.20712] [PMID]
  112. Witwer KW, Watson AK, Blankson JN, Clements JE. Relationships of PBMC microRNA expression, plasma viral load, and CD4+ T-cell count in HIV-1-infected elite suppressors and viremic patients. Retrovirology. 2012;9:5. [DOI:10.1186/1742-4690-9-5] [PMID] [PMCID]
  113. Anadol E, Schierwagen R, Elfimova N, Tack K, Schwarze-Zander C, Eischeid H, et al. Circulating microRNAs as a marker for liver injury in human immunodeficiency virus patients. Hepatology (Baltimore, Md. 2015;61(1):46-55. [DOI:10.1002/hep.27369] [PMID]