An open pilot study exploring the efficacy of fluvastatin, pegylated interferon and ribavirin in patients with hepatitis C virus genotype 1b in high viral loads

Intervirology

Volumn 52, Issue 1, 2009, Pages 43-48

  Sezaki, Hitomi ^a   Suzuki, Fumitaka ^a   Akuta, Norio ^a   Yatsuji, Hiromi ^a   Hosaka, Tetsuya ^a   Kobayashi, Masahiro ^a   Suzuki, Yoshiyuki ^a   Arase, Yasuji ^a   Ikeda, Kenji ^a   Miyakawa, Yuzo ^b   Kumada, Hiromitsu ^a  

^a TORANOMON HOSPITAL   (Japan)

^b Miyakawa Memorial Research Foundation   (Japan)

Author keywords

Hepatitis, chronic; Interferon, pegylated; Ribavirin; Statin; Virus, hepatitis C

Indexed keywords

FLUINDOSTATIN; PEGINTERFERON ALPHA2B; RIBAVIRIN; VIRUS RNA;

ADD ON THERAPY; ADULT; ARTICLE; CLINICAL ARTICLE; CONTROLLED STUDY; DRUG EFFICACY; FEMALE; GENOTYPE; HEPATITIS C; HEPATITIS C VIRUS; HUMAN; MALE; PILOT STUDY; PRIORITY JOURNAL; TREATMENT RESPONSE; VIROLOGY; VIRUS LOAD;

ADULT; ANTIVIRAL AGENTS; DRUG THERAPY, COMBINATION; FATTY ACIDS, MONOUNSATURATED; FEMALE; GENOTYPE; HEPACIVIRUS; HEPATITIS C, CHRONIC; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; INDOLES; INTERFERON ALFA-2A; MALE; MIDDLE AGED; PILOT PROJECTS; POLYETHYLENE GLYCOLS; RIBAVIRIN; RNA, VIRAL; TREATMENT OUTCOME; VIRAL LOAD;

HEPATITIS C VIRUS; HEPATITIS C VIRUS GENOTYPE 1;

EID: 64549132866     PISSN: 03005526     EISSN: None     Source Type: Journal    
DOI: 10.1159/000213504     Document Type: Article

References (48)

1. Cohen J: The scientific challenge of hepatitis C. Science 1999; 285:26-30.
2. Seeff LB: Natural history of chronic hepatitis C. Hepatolog y 2002; 36:S35-S46.
3. Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL Jr, Haussinger D, Diago M, Carosi G, Dhumeaux D, Craxi A, Lin A, Hoffman J, Yu J: Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002; 347: 975-982.
4. Hadziyannis SJ, Sette H Jr, Morgan TR, Ba-lan V, Diago M, Marcellin P, Ramadori G, Bodenheimer H Jr, Bernstein D, Rizzetto M, Zeuzem S, Pockros PJ, Lin A, Ackrill AM: Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. A nn Intern Med 2004; 140 : 346-355.
5. Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M , Reindollar R , Goodman ZD, Koury K, Ling M, Albrecht JK: Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001; 358:958-965.
6. Kanwal F, Hoang T, Spiegel BM, Eisen S, Dominitz JA, Gifford A, Goetz M, Asch SM: Predictors of treatment in patients with chronic hepatitis C infection - role of patient versus nonpatient factors. Hepatology 2007; 46: 1741-1749.
7. Poynard T, Bedossa P, Opolon P: Natural history of liver fibrosis progression in patients with chronic hepatitis C. Lancet 1997; 349: 825-832.
8. Conjeevaram HS, Fried MW, Jeffers LJ, Terrault NA, Wiley-Lucas TE, Afdhal N, Brown RS, Belle SH, Hoofnagle JH, Kleiner DE, Howell CD: Peginterferon and ribavirin treatment in African American and Caucasian American patients with hepatitis C genotype 1. Gastroenterology 2006; 131:470-477.
9. Tsubota A, Chayama K, Ikeda K, Yasuji A, Koida I, Saitoh S, Hashimoto M, Iwasaki S, Kobayashi M, Hiromitsu K: Factors predictive of response to interferon-alpha therapy in hepatitis C virus infection. Hepatology 1994; 19:1088-1094.
10. Sezaki H, Suzuki F, Kawamura Y, Yatuji H, Hosaka T, Akuta N, Kobayashi M, Suzuki Y, Saitoh S, Arase Y, Ikeda K, Miyakawa Y, Kumada H: Poor response to pegylated interferon and ribavirin in aged women infected with hepatitis C virus of genotype 1b in high viral loads. Dig Dis Sci, in press.
11. Lawitz E, Rodriguez-Torres M, Muir AJ, Kieffer TL, McNair L, Khunvichai A, Mc-Hutchison JG: Antiviral effects and safety of telaprevir, peginterferon alfa-2a, and ribavirin for 28 days in hepatitis C patients. J Hepatol 2008; 49: 163-169.
12. Forestier N, Reesink HW, Weegink CJ, Mc-Nair L, Kieffer TL, Chu HM, Purdy S, Jansen PL, Zeuzem S: Antiviral activity of telaprevir (VX-950) and peginterferon alfa-2a in patients wit h hepatitis C. Hepatolog y 2007; 46: 640-648.
13. Bader T, Fazili J, Madhoun M, Aston C, Hughes D, Rizvi S, Seres K, Hasan M: Fluvastatin inhibits hepatitis C replication in humans. Am J Gastroenterol 2008; 103:1383-1389.
14. Ikeda M, Abe K, Yamada M, Dansako H, NakaK, Kato N: Different anti-HCV profiles of statins and their potential for combination therapy with interferon. Hepatology 2006; 44:117-125.
15. Yoshizawa H, Tanaka J, Miyakawa Y: National prevention of hepatocellular carcinoma in Japan based on epidemiology of hepatitis C virus infection in the general0 population. Intervirology 2006; 49: 7-17.
16. Akuta N, Suzuki F, Kawamura Y, Yatsuji H, Sezaki H, Suzuki Y, Hosaka T, Kobayashi M, Kobayashi M, Arase Y, Ikeda K, Kumada H: Predictors of viral kinetics to peginterferon plus ribavirin combination therapy in Japanese patients infected with hepatitis C virus genotype 1b. J Med Virol 2007; 79:1686-1695.
17. Sezaki H, Suzuki F, Kawamura Y, Yatsuji H, Hosaka T, Akuta N, Kobayashi M, Suzuki Y, Arase Y, Ikeda K, Kumada H: Evaluation of long-term biochemical responses to combination therapy of interferon plus ribavirin in those infected with hepatitis C virus genotype 1b and high baseline viral load. Hepatol Res 2007; 37: 787-792.
18. Enomoto N, Sakuma I, Asahina Y, Kurosaki M, Muraka mi T, Yamamoto C, Ogura Y, Izumi N, Marumo F, Sato C: Mutations in the nonstructural protein 5A gene and response to interferon in patients with chronic hepatitis C virus 1b infection. N Engl J Med 1996; 334: 77-81.
19. Goldstein JL, Brown MS: Regulation of the mevalonate pathway. Nature 1990; 343:425-430.
20. Istvan ES, Deisenhofer J: Structural mechanism for statin inhibition of HMG-CoA reductase. Science 2001; 292: 1160-1164.
21. Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, Joyal SV, Hill KA, Pfeffer MA, Skene AM: Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004; 350: 1495-1504.
22. Grundy SM, Cleeman JI, Merz CN, Brewer HB Jr, Clark LT, Hunninghake DB, Pasternak RC, Smith SC Jr, Stone NJ: Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. J Am Coll Cardiol 2004; 44: 720-732.
23. de Denus S, Spinler SA, Miller K, Peterson AM: Statins and liver toxicity: a meta-analy-sis. Pharmacotherapy 2004; 24: 584-591.
24. O'Leary JG, Chan JL, McMahon CM, Chung RT: Atorvastatin does not exhibit antiviral activity against HCV at conventional doses: a pilot clinical trial. Hepatology 2007; 45: 895-898.
25. Akuta N, Suzuki F, Kawamura Y, Yatsuji H, Sezaki H, Suzuki Y, Hosaka T, Kobayashi M, Kobayashi M, Arase Y, Ikeda K, Miyakawa Y, Kumada H: Prediction of response to pegylated interferon and ribavirin in hepatitis C by polymorphisms in the viral core protein and very early dynamics of viremia. Intervirology 2007; 50: 361-368.
26. Poynard T, Marcellin P, Lee SS, Niederau C, Minuk GS, Ideo G, Bain V, Heathcote J, Zeuzem S, Trepo C, Albrecht J: Randomised trial of interferon alpha2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. Lancet 1998; 352: 1426 - 1432.
27. Yasuda M, Shimizu I, Shiba M, Ito S: Suppressive effects of estradiol on dimethylni-trosamine-induced fibrosis of the liver in rats. Hepatolog y 1999; 29: 719-727.
28. Khosla S, Melton LJ 3rd, Atkinson EJ, O'Fallon WM, Klee GG, Riggs BL: Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women: a key role for bioavailable estrogen. J Clin Endocrinol Metab 1998; 83: 2266-2274.
29. Need AG, O'Loughlin PD, Morris HA, Horowitz M, Nordin BE: The effects of age and other variables on serum parathyroid hormone in postmenopausal women attending an osteoporosis center. J Clin Endocrinol Metab 2004; 89:1646-1649.
30. Siris ES, Brenneman SK, Barrett-Connor E, Miller PD, Sajjan S, Berger ML, Chen YT: The effect of age and bone mineral density on the absolute, excess, and relative risk of fracture in postmenopausal women aged 50-99: results from the National Osteoporosis Risk Assessment (NORA). Osteoporos Int 2006; 17:565-574.
31. Khorashadi S, Hasson NK, Cheung RC: Incidence of statin hepatotoxicity in patients with hepatitis C. Clin Gastroenterol Hepatol 2006; 4: 902-907.
32. Corsini A, Bellosta S, Baetta R, Fumagalli R, Paoletti R, Bernini F: New insights into the pharmacodynamic and pharmacokinetic properties of statins. Pharmacol Ther 1999; 84: 413-428.
33. Andre P, Komurian-Pradel F, Deforges S, Perret M, Berland JL, Sodoyer M, Pol S, Brechot C, Paranhos-Baccala G, Lotteau V: Characterization of low- and very-low-density hepatitis C virus RNA-containing particles. J Virol 2002; 76 : 6919-6928.
34. Molina S, Castet V, Fournier-Wirth C, Pich-ard-Garcia L, Avner R, Harats D, Roitelman J, Barbaras R, Graber P, Ghersa P, Smolarsky M, Funaro A, Malavasi F, Larrey D, Coste J, Fabre JM, Sa-Cunha A, Maurel P: The low-density lipoprotein receptor plays a role in the infection of primary human hepatocytes by hepatitis C virus. J Hepatol 2007; 46: 411-419.
35. Agnello V, Abel G, Elfahal M, Knight GB, Zhang QX: Hepatitis C virus and other flaviviridae viruses enter cells via low density lipoprotein receptor. Proc Natl Acad Sci USA 1999; 96: 12766-12771.
36. Monazahian M, Bohme I, Bonk S, Koch A, Scholz C, Grethe S, Thomssen R: Low density lipoprotein receptor as a candidate receptor for hepatitis C virus. J Med Virol 1999; 57:223-229.
37. Aizaki H, Lee KJ, Sung VM, Ishiko H, Lai MM: Characterization of the hepatitis C virus RNA replication complex associated with lipid rafts. Virology 2004; 324:450-461.
38. Miyanari Y, Atsuzawa K, Usuda N, Watashi K, Hishiki T, Zayas M, Bartenschlager R, Wakita T, Hijikata M, Shimotohno K: The lipid droplet is an important organelle for hepatitis C virus production. Nat Cell Biol 2007; 9:1089-1097.
39. Akuta N, Suzuki F, Kawamura Y, Yatsuji H, Sezaki H, Suzuki Y, Hosaka T, Kobayashi M, Kobayashi M, Arase Y, Ikeda K, Kumada H: Predictive factors of early and sustained responses to peginterferon plus ribavirin combination therapy in Japanese patients infected with hepatitis C virus genotype 1b: amino acid substitutions in the core region and low-density lipoprotein cholesterol levels. J Hepatol 2007; 46: 403-410.
40. Gopal K, Johnson TC, Gopal S, Walfish A, Bang CT, Suwandhi P, Pena-Sahdala HN, Clain DJ, Bodenheimer HC Jr, Min AD: Correlation between beta-lipoprotein levels and outcome of hepatitis C treatment. Hepatology 2006; 44: 335-340.
41. Zhang FL, Casey PJ: Protein prenylation: molecular mechanisms and functional consequences. Annu Rev Biochem 1996; 65:241-269.
42. Kapadia SB, Chisari FV: Hepatitis C virus RNA replication is regulated by host geranylgeranylation and fatty acids. Proc Natl Acad Sci USA 2005; 102:2561-2566.
43. Wang C, Gale M Jr, Keller BC, Huang H, Brown MS, Goldstein JL, Ye J: Identification of FBL2 as a geranylgeranylated cellular protein required for hepatitis C virus RNA replicat ion. Mol Cel l 2005; 18 : 425-434.
44. Ye J, Wang C, Sumpter R Jr, Brown MS, Goldstein JL, Gale M Jr: Disruption of hepatitis C virus RNA replication through inhibition of host protein geranylgeranylation. Proc Natl Acad Sci USA 2003; 100 : 15865-15870.
45. Wolozin B, Kellman W, Ruosseau P, Celesia GG, Siegel G: Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors. Arch Neurol 2000; 57: 1439-1443.
46. Jick H, Zornberg GL, Jick SS, Seshadri S, Drachman DA: Statins and the risk of dementia. Lancet 2000; 356:1627-1631.
47. Vaughan CJ: Prevention of stroke and dementia with statins: effects beyond lipid lowering. Am J Cardiol 2003; 91 : 23B-29B.
48. Liao JK, Laufs U: Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol 2005; 45:89-118.