The pharmacology and activity of non-steroidal anti-inflammatory drugs (NSAIDs): A review of their use as an adjuvant treatment in patients with HBV and HCV chronic hepatitis

Italian Journal of Medicine

Volumn 5, Issue 2, 2011, Pages 82-89

  Fiorino, Sirio ^a   Cursaro, Carmela ^b   Lorenzini, Stefania ^b   Loggi, Elisabetta ^b   Brodosi, Lucia ^b   Cattani, Laura ^a   Cuppini, Andrea ^a   Bernardi, Mauro ^b   Andreone, Pietro ^b  

^a Azienda USL di Bologna   (Italy)

^b UNIVERSITY OF BOLOGNA   (Italy)

Author keywords

Chronic hepatitis; Hepatitis B Virus; Hepatitis C Virus; Non steroidal anti inflammatory drugs (NSAIDs); Prostaglandin E2

Indexed keywords

ACETYLSALICYLIC ACID; ALPHA INTERFERON; ALPHA2B INTERFERON; BETA INTERFERON; CYTOKINE; DICLOFENAC; GAMMA INTERFERON; IBUPROFEN; INDOMETACIN; INTERLEUKIN 12; INTERLEUKIN 2; JANUS KINASE; KETOPROFEN; MITOGEN ACTIVATED PROTEIN KINASE 1; NAPROXEN; NITRIC OXIDE; NONSTEROID ANTIINFLAMMATORY AGENT; PIROXICAM; PROSTAGLANDIN E2; PROSTAGLANDIN H2; RIBAVIRIN; STAT PROTEIN; TENOXICAM; TUMOR NECROSIS FACTOR ALPHA;

ADJUVANT THERAPY; ANEMIA; ASTHENIA; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CHRONIC HEPATITIS; DOWN REGULATION; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG SAFETY; DRUG USE; EPIGASTRIC PAIN; FLU LIKE SYNDROME; HEPATITIS B; HEPATITIS B VIRUS; HEPATITIS C; HEPATITIS C VIRUS; HUMAN; IMMUNE SYSTEM; INFLAMMATION; NEGATIVE FEEDBACK; OXIDATIVE STRESS; RANDOMIZED CONTROLLED TRIAL (TOPIC); RECURRENT INFECTION; REVIEW; TH1 CELL; VIRUS REPLICATION;

EID: 79957890141     PISSN: 18779344     EISSN: 18779352     Source Type: Journal    
DOI: 10.1016/j.itjm.2011.02.004     Document Type: Review

References (82)

1. Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology 2007;45(2):507-39. (Pubitemid 46374607)
2. Lauer GM, Walker BD. Hepatitis C virus infection. N Engl J Med 2001;345(1):41-52. (Pubitemid 32634271)
3. Fattovich G, Giustina G, Schalm SW, Hadziyannis S, Sanchez-Tapias J, Almasio P, et al. Occurrence of hepatocellular carcinoma and decompensation in western European patients with cirrhosis type B. The EUROHEP Study Group on Hepatitis B Virus and Cirrhosis. Hepatology 1995;21:77-82.
4. Di Marco V, Lo Iacono O, Camma C, Vaccaro A, Giunta M, Martorana G, et al. The long-term course of chronic hepatitis B. Hepatology 1999;30:257-64. (Pubitemid 29300594)
5. Baumert TF, Thimme R, von Weizsacker F. Pathogenesis of hepatitis B virus infection. World J Gastroenterol 2007;13:82-90. (Pubitemid 46165465)
6. [No authors listed] G lobal surveillance and control of hepatitis C. Report of a WHO Consultation organized in collaboration with the Viral Hepatitis Prevention Board, Antwerp, Belgium. J Viral Hepat. 1999;6(1):35-47.
7. Tong MJ, el-Farra NS, Reikes AR, Co RL. Clinical outcomes after transfusion-associated hepatitis C. N Engl J Med 1995;332(22):1463-6.
8. Poynard T, Bedossa P, Chevallier M, Mathurin P, Lemonnier C, Trepo C, et al. A comparison of three interferon alfa-2b regimens for the long-term treatment of chronic non-A, non-B hepatitis. Multicenter Study Group. N Engl J Med 1995;332(22):1457-62.
9. Di Bisceglie AM, Martin P, Kassianides C, Lisker-Melman M, Murray L, Waggoner J, et al. Recombinant interferon alfa therapy for chronic hepatitis C. A randomized, double-blind, placebo-controlled trial. N Engl J Med 1989;321(22):1506-10.
10. Shiffman ML, Ghany MG, Morgan TR, Wright EC, Everson GT, Lindsay KL, et al. Impact of reducing peginterferon alfa-2a and ribavirin dose during retreatment in patients with chronic hepatitis C. Gastroenterology 2007;132(1):103-12. (Pubitemid 46127673)
11. Shiffman ML, Di Bisceglie AM, Lindsay KL, Morishima C, Wright EC, Everson GT, et al., Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis Trial Group. Peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior treatment. Gastroenterology 2004;126(4):1015-23.
12. Lange CM, Sarrazin C, Zeuzem S. Review article: specifically targeted anti-viral therapy for hepatitis C - a new era in therapy. Aliment Pharmacol Ther 2010;32(1):14-28.
13. Milazzo L, Antinori S. STAT-C: a full revolution or just a step forward? Lancet 2010;376(9742):662-3.
14. Gaudieri S, Rauch A, Pfafferott K, Barnes E, Cheng W, McCaughan G, et al. Hepatitis C virus drug resistance and immune-driven adaptations: relevance to new antiviral therapy. Hepatology 2009;49(4):1069-82.
15. Giambartolomei S, Artini M, Almerighi C, Moavero SM, Levrero M, Balsano C. Nonsteroidal anti-inflammatory drug metabolism potentiates interferon alfa signaling by increasing STAT1 phosphorylation. Hepatology 1999;30(2):510-6. (Pubitemid 29357518)
16. Bahrami H, Daryani NE, Haghpanah B, Moayyeri A, Moghadam KF, Mirmomen S, et al. Effects of indomethacin on viral replication markers in asymptomatic carriers of hepatitis B: a randomized, placebo-controlled trial. Am J Gastroenterol 2005;100(4):856-61. (Pubitemid 40592379)
17. Andreone P, Gramenzi A, Loggi E, Favarelli L, Cursaro C, Margotti M, et al. In vitro effect of indomethacin and interferon-alpha on Th1 and Th2 cytokine synthesis in patients with chronic hepatitis C. Cytokine 2004;26(3):95-101.
18. Andreone P, Gramenzi A, Cursaro C, Biselli M, Lorenzini S, Loggi E, et al. Interferon-alpha combined with ketoprofen as treatment of naïve patients with chronic hepatitis C: a randomized controlled trial. J Viral Hepat 2003;10(4):306-9. (Pubitemid 36801918)
19. Andreone P, Cursaro C, Gramenzi A, Fiorino S, Di Giammarino L, Miniero R, et al. Interferon alpha plus ketoprofen or interferon alpha plus ribavirin in chronic hepatitis C non-responder to interferon alpha alone: results of a pilot study. Ital J Gastroenterol Hepatol 1999;31(8):688-94.
20. Andreone P, Cursaro C, Gramenzi A, Buzzi A, Miniero R, Sprovieri G, et al. Indomethacin enhances serum 2′5′-oligoadenylate synthetase in patients with hepatitis B and C virus chronic active hepatitis. J Hepatol 1994;21(6):984-8.
21. Andreone P, Cursaro C, Gasbarrini G. Interferon alpha increases prostaglandin E2 production by cultured liver biopsy in patients with chronic viral hepatitis: can non-steroidal anti-inflammatory drugs improve the therapeutic response to interferon? J Hepatol 1993;19(2):228-31.
22. Weber F, Kochs G, Haller O. Inverse interference: how viruses fight the interferon system. Viral Immunol 2004;17(4):498-515. (Pubitemid 40054230)
23. Haller O, Kochs G, Weber F. The interferon response circuit: induction and suppression by pathogenic viruses. Virology 2006;344(1):119-30. (Pubitemid 41814456)
24. Vercammen E, Staal J, Beyaert R. Sensing of viral infection and activation of innate immunity by toll-like receptor 3. Clin Microbiol Rev 2008;21(1):13-25. (Pubitemid 351160008)
25. Halwani R, Doroudchi M, Yassine-Diab B, Janbazian L, Shi Y, Said EA, et al. Generation and maintenance of human memory cells during viral infection. Springer Semin Immunopathol 2006;28(3):197-208. (Pubitemid 44764276)
26. Stockinger B, Bourgeois C, Kassiotis G. CD4+ memory T cells: functional differentiation and homeostasis. Immunol Rev 2006;211:39-48. (Pubitemid 43882959)
27. Smith PL, Lombardi G, Foster GR. Type I interferons and the innate immune response-more than just antiviral cytokines. Mol Immunol 2005;42(8):869-77. (Pubitemid 40489010)
28. Alcami A, Koszinowski UH. Viral mechanisms of immune evasion. Mol Med Today 2000;6(9):365-72.
29. Blackburn SD, Wherry EJ. IL-10, T cell exhaustion and viral persistence. Trends Microbiol 2007;15(4):143-6.
30. Loo YM, Gale Jr M. Viral regulation and evasion of the host response. Curr Top Microbiol Immunol 2007;316:295-313.
31. Sharma-Walia N, Raghu H, Sadagopan S, Sivakumar R, Veettil MV, Naranatt PP, et al. Cyclooxygenase 2 induced by Kaposi's sarcoma-associated herpesvirus early during in vitro infection of target cells plays a role in the maintenance of latent viral gene expression. J Virol 2006;80(13):6534-52. (Pubitemid 43927455)
32. Zhu H, Cong JP, Yu D, Bresnahan WA, Shenk TE. Inhibition of cyclooxygenase 2 blocks human cytomegalovirus replication. Proc Natl Acad Sci U S A 2002;99(6):3932-7. (Pubitemid 34252208)
33. Gosselin J, Borgeat P. Epstein-Barr virus modulates 5-lipoxygenase product synthesis in human peripheral blood mononuclear cells. Blood 1997;89(6):2122-30. (Pubitemid 27132129)
34. Vaddadi KS, Das UN. HIV virus, prostaglandins and essential fatty acids; a suggested mechanism for T helper cell penetration. Med Hypotheses 1988;26(4):229-30.
35. Rehermann B, Nascimbeni M. Immunology of hepatitis B virus and hepatitis C virus infection. Nat Rev Immunol 2005;5(3):215-29. (Pubitemid 40364823)
36. Waris G, Siddiqui A. Regulatory mechanisms of viral hepatitis B and C. J Biosci 2003;28(3):311-21. (Pubitemid 36512806)
37. Ray N, Bisher ME, Enquist LW. Cyclooxygenase-1 and -2 are required for production of infectious pseudorabies virus. J Virol 2004;78(23):12964-7.
38. Davy C, Doorbar J. G2/M cell cycle arrest in the life cycle of viruses. Virology 2007;368(2):219-26. (Pubitemid 350016216)
39. Alcami A, Koszinowski UH. Viral mechanisms of immune evasion. Trends Microbiol 2000;8(9):410-8.
40. Murakami M, Kudo I. Prostaglandin E synthase: a novel drug target for inflammation and cancer. Curr Pharm Des 2006;12(8):943-54.
41. Bos CL, Richel DJ, Ritsema T, Peppelenbosch MP, Versteeg HH. Prostanoids and prostanoid receptors in signal transduction. Int J Biochem Cell Biol 2004;36(7):1187-205. (Pubitemid 38515660)
42. Le Page C, Génin P, Baines MG, Hiscott J. Interferon activation and innate immunity. Rev Immunogenet 2000;2(3):374-86. (Pubitemid 32041163)
43. Siegal FP, Kadowaki N, Shodell M, Fitzgerald-Bocarsly PA, Shah K, Ho S, et al. The nature of the principal type 1 interferon-producing cells in human blood. Science 1999;284(5421):1835-7.
44. Randall RE, Goodbourn S. Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures. J Gen Virol 2008;89(Pt 1):1-47.
45. Xu D, Qu CK. Protein tyrosine phosphatases in the JAK/STAT pathway. Front Biosci 2008;13:4925-32. (Pubitemid 351599646)
46. Murray PJ. The JAK-STAT signaling pathway: input and output integration. J Immunol 2007;178(5):2623-9. (Pubitemid 46333135)
47. Flati V, Haque SJ, Williams BR. Interferon-alpha-induced phosphorylation and activation of cytosolic phospholipase A2 is required for the formation of interferon-stimulated gene factor three. EMBO J 1996;15(7):1566-71.
48. Hannigan GE, Williams BR. Signal transduction by interferonalpha through arachidonic acid metabolism. Science 1991;251(4990):204-7. (Pubitemid 21916871)
49. Hii CS, Ferrante A, Edwards YS, Huang ZH, Hartfield PJ, Rathjen DA, et al. Activation of mitogen-activated protein kinase by arachidonic acid in rat liver epithelial WB cells by a protein kinase C-dependent mechanism. J Biol Chem 1995;270(9):4201-4.
50. Wen Z, Zhong Z, Darnell Jr JE. Maximal activation of transcription by Stat1 and Stat3 requires both tyrosine and serine phosphorylation. Cell 1995;82(2):241-50.
51. Williams CS, Mann M, DuBois RN. The role of cyclooxygenases in 'inflammation, cancer, and development. Oncogene 1999;18(55):7908-16. (Pubitemid 30066236)
52. Dubois RN, Abramson SB, Crofford L, Gupta RA, Simon LS, Van De Putte LB, et al. Cyclooxygenase in biology and disease. FASEB J 1998;12(12):1063-73. (Pubitemid 28418937)
53. Waris G, Siddiqui A. Hepatitis C virus stimulates the expression of cyclooxygenase-2 via oxidative stress: role of prostaglandin E2 in RNA replication. J Virol 2005;79(15):9725-34. (Pubitemid 41022315)
54. Koike K. Hepatitis C virus contributes to hepatocarcinogenesis by modulating metabolic and intracellular signaling pathways. J Gastroenterol Hepatol 2007;22(Suppl 1):S108-11.
55. Waris G, Livolsi A, Imbert V, Peyron JF, Siddiqui A. Hepatitis C virus NS5A and subgenomic replicon activate NF-kappaB via tyrosine phosphorylation of IkappaBalpha and its degradation by calpain protease. J Biol Chem 2003;278(42):40778-87. (Pubitemid 37280895)
56. Smith WL, Garavito RM, DeWitt DL. Prostaglandin endoperoxide H synthases (cyclooxygenases)-1 and -2. J Biol Chem 1996;271(52):33157-60. (Pubitemid 27010118)
57. Cheng AS, Chan HL, Leung WK, To KF, Go MY, Chan JY, et al. Expression of HBx and COX-2 in chronic hepatitis B, cirrhosis and hepatocellular carcinoma: implication of HBx in upregulation of COX-2. Mod Pathol 2004;17(10):1169-79. (Pubitemid 39312943)
58. Cheng AS, Chan HL, Leung NW, Liew CT, To KF, Lai PB, et al. Expression of cyclooxygenase-2 in chronic hepatitis B and the effects of anti-viral therapy. Aliment Pharmacol Ther 2002;16(2):251-60. (Pubitemid 34146366)
59. Pereira CF, Boven LA, Middel J, Verhoef J, Nottet HS. Induction of cyclooxygenase-2 expression during HIV-1-infected monocyte-derived macrophage and human brain microvascular endothelial cell interactions. J Leukoc Biol 2000;68(3):423-8.
60. Janelle ME, Gravel A, Gosselin J, Tremblay MJ, Flamand L. Activation of monocyte cyclooxygenase-2 gene expression by human herpesvirus 6. Role for cyclic AMP-responsive element-binding protein and activator protein-1. J Biol Chem 2002;277(34):30665-74. (Pubitemid 34970762)
61. Murono S, Inoue H, Tanabe T, Joab I, Yoshizaki T, Furukawa M, et al. Induction of cyclooxygenase-2 by Epstein-Barr virus latent membrane protein 1 is involved in vascular endothelial growth factor production in nasopharyngeal carcinoma cells. Proc Natl Acad Sci U S A 2001;98(12):6905-10. (Pubitemid 32538315)
62. Meydani SN, Han SN, Wu D. Vitamin E and immune response in the aged: molecular mechanisms and clinical implications. Immunol Rev 2005;205:269-84. (Pubitemid 40789949)
63. Barrios-Rodiles M, Chadee K. Novel regulation of cyclooxygenase-2 expression and prostaglandin E2 production by IFN-gamma in human macrophages. J Immunol 1998;161(5):2441-8. (Pubitemid 28397060)
64. Mahic M, Yaqub S, Johansson CC, Taskén K, Aandahl EM. FOXP3+CD4+CD25+ adaptive regulatory T cells express cyclooxygenase-2 and suppress effector T cells by a prostaglandin E2-dependent mechanism. J Immunol 2006;177(1):246-54. (Pubitemid 43939136)
65. Katamura K, Shintaku N, Yamauchi Y, Fukui T, Ohshima Y, Mayumi M, et al. Prostaglandin E2 at priming of naive CD4+ T cells inhibits acquisition of ability to produce IFN-gamma and IL-2, but not IL-4 and IL-5. J Immunol 1995;155(10):4604-12. (Pubitemid 3010794)
66. Reiss CS, Komatsu T. Does nitric oxide play a critical role in viral infections? J Virol 1998;72(6):4547-51.
67. Fuji A, Kakumu S, Ohtani Y, Murase K, Hirofuji H, Tahara H. Interferon-gamma production by peripheral blood mononuclear cells of patients with chronic liver disease. Hepatology 1987;7(3):577-81. (Pubitemid 17073168)
68. Flowers M, Sherker A, Sinclair SB, Greig PD, Cameron R, Phillips MJ, et al. Prostaglandin E in the treatment of recurrent hepatitis B infection after orthotopic liver transplantation. Transplantation 1994;58(2):183-92.
69. Tsuboi I, Tanaka H, Nakao M, Shichijo S, Itoh K. Nonsteroidal anti-inflammatory drugs differentially regulate cytokine production in human lymphocytes: up-regulation of TNF, IFNgamma and IL-2, in contrast to down-regulation of IL-6 production. Cytokine 1995;7(4):372-9.
70. Kantor TG. Ketoprofen: a review of its pharmacologic and clinical properties. Pharmacotherapy 1986;6(3):93-103. (Pubitemid 16003473)
71. Jamali F, Brocks DR. Clinical pharmacokinetics of ketoprofen and its enantiomers. Clin Pharmacokinet 1990;19(3):197-217. (Pubitemid 20281450)
72. Caldwell JR. Comparison of the efficacy, safety, and pharmacokinetic profiles of extended-release ketoprofen and piroxicam in patients with rheumatoid arthritis. Clin Ther 1994;16(2):222-35. (Pubitemid 24321659)
73. Tanabe T, Tohnai N. Cyclooxygenase isozymes and their gene structures and expression. Prostaglandins Other Lipid Mediat 2002;68-69:95-114. (Pubitemid 35247390)
74. Andreone P, Gramenzi A, Cursaro C, Bernardi M. Inhibition of the cyclooxygenase/lipoxygenase pathways to improve interferon alpha efficacy in chronic hepatitis C: don't lose the tract! Dig Liver Dis 2000;32(6):542-3.
75. Andreone P, Cursaro C, Gramenzi A, Miniero R, Bernardi M, Gasbarrini G. Interferon-alpha plus indomethacin combined therapy in HBeAg positive chronic hepatitis B non-responder to a previous IFN-alpha course: results of a pilot study. International Hepatology Communications July 1996;5(3):151-9. (Pubitemid 26280898)
76. Trujillo-Murillo K, Rincón-Sánchez AR, Martínez- Rodríguez H, Bosques-Padilla F, Ramos-Jiménez J, Barrera-Saldaña HA, et al. Acetylsalicylic acid inhibits hepatitis C virus RNA and protein expression through cyclooxygenase 2 signaling pathways. Hepatology 2008;47(5):1462-72. (Pubitemid 351702730)
77. Kapicioǧlu S, Sari M, Kaynar K, Baki A, Ozoran Y. The effect of indomethacin on hepatitis B virus replication in chronic healthy carriers. Scand J Gastroenterol 2000;35(9):957-9.
78. Anderson FH, Zeng L, Yoshida EM, Rock NR. Failure of ketoprofen and interferon combination therapy to improve interferon-resistant chronic hepatitis C. Can J Gastroenterol 1997;11(4):294-7. (Pubitemid 27263187)
79. Zarski JP, Maynard-Muet M, Chousterman S, Baud M, Barnoud R, Abergel A, et al. Tenoxicam, a non-steroid anti-inflammatory drug, is unable to increase the response rate in patients with chronic hepatitis C treated by alpha interferon. Hepatology 1998;27(3):862-7.
80. Fabris P, Tositti G, Negro F, Marranconi F, Infantolino D, Rassu M, et al. Interferon alfa-2b alone or in combination with ketoprofen as treatment for interferon-naive chronic hepatitis C patients. Aliment Pharmacol Ther 1999;13(10):1329-34. (Pubitemid 29462308)
81. Muñoz AE, Levi D, Podestá A, Gorín JM, González J, Bartellini MA, et al. Interferon-alpha 2b combined with daily ketoprofen administration improves virological response in chronic hepatitis C: a prospective and randomised trial. Gut 2000;46(3):427-31. (Pubitemid 30313399)
82. Gramenzi A, Cursaro C, Margotti M, Balsano C, Spaziani A, Anticoli S, et al. Ketoprofen, peginterferon 2a and ribavirin for genotype 1 chronic hepatitis C: a phase II study. World J Gastroenterol 2009;15(47):5946-52.