Treatment strategies for chronic hepatitis C virus infection

Journal of Gastroenterology

Volumn 35, Issue 6, 2000, Pages 411-423

  Kasahara, Akinori ^a  

^a OSAKA UNIVERSITY HOSPITAL   (Japan)

Author keywords

Chronic hepatitis C; Hepatocellular carcinoma; Interferon

Indexed keywords

ALPHA INTERFERON; BETA INTERFERON; GLYCYRRHIZIC ACID; INTERFERON; IRON; LYMPHOBLAST INTERFERON; RECOMBINANT ALPHA2A INTERFERON; RECOMBINANT ALPHA2B INTERFERON; RIBAVIRIN; URSODEOXYCHOLIC ACID; XIAO CHAI HU TANG;

DISEASE COURSE; DOSE RESPONSE; DRUG EFFICACY; DRUG INDICATION; ERADICATION THERAPY; HEMOLYTIC ANEMIA; HEPATITIS C; HUMAN; INCIDENCE; JAPAN; LIVER CELL CARCINOMA; MORTALITY; PRIORITY JOURNAL; REVIEW; VIRUS LOAD;

EID: 0033917629     PISSN: 09441174     EISSN: None     Source Type: Journal    
DOI: 10.1007/s005350070085     Document Type: Review

References (110)

1. Hagiwara H, Hayashi N, Mita E, Naito M, Kasahara A, Fusamoto H, et al. Quantitation of hepatitis C virus RNA in serum of asymptomatic blood donors and patients with type C chronic liver disease. Hepatology 1993;17:545-50.
2. Yokosuka O, Kato N, Hosoda K, Ito Y, Imazeki F. Ohto M, et al. Efficacy of long-term interferon treatment in chronic liver disease evaluated by polymerase chain reaction assay for hepatitis C virus RNA. Gut 1996;37:721-6.
3. DiBisceglie AM, Goodman ZD, Ishak KG, Hoofnagle JH, Melpolder JJ, Alter HJ. Long-term clinical and histological follow-up of chronic posttransfusion hepatitis. Hepatology 1991; 14:969-74.
4. Poynard T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. Lancet 1997; 349:825-32.
5. Kiyosawa K, Sodeyama T, Tanaka E, Gibo Y, Yoshizawa K, Nagano Y, et al. Interrelationship of blood transfusion, non-A, non-B hepatitis and hepatocellular carcinoma. Analysis by detection of antibody to hepatitis C virus. Hepatology 1990;12: 671-5.
6. Tsukuma H, Hiyama T, Tanaka S, Nakano M, Yabuuchi T, Kitayama T, et al. Risk factors for hepatocellular carcinoma among patients with chronic liver disease. N Engl J Med 1993; 328:1797-801.
7. Ikeda K, Saitoh S, Koida I, Arase Y, Tsubota A, Chayama K, et al. A multivariate analysis of risk factors for hepatocellular carcinogenesis: a prospective observation of 795 patients with viral and alcoholic cirrhosis. Hepatology 1993;18:47-53.
8. Takano S, Yokosuka O, Imazeki F, Tagawa M, Omata M. Incidence of hepatocellular carcinoma in chronic hepatitis B and C. A prospective study of 251 patients. Hepatology 1995;21:650-5.
9. Darmell JE. STATs and gene regulation. Science 1997;277:1630-5.
10. Hagiwara H, Hayashi N, Mita E, Takehara T, Kasahara A, Fusamoto H, et al. Quantitative analysis of hepatitis C virus RNA in serum during interferon alfa therapy. Gastroenterology 1993;104:877-83.
11. Clemens MJ, Elia A. The double-stranded RNA-dependent protein kinase PKR: structure and function. J Interferon Cytokine 1997;17:503-24.
12. Naito M, Hayashi N, Hagiwara H, Hiramatsu N, Kasahara A, Fusamoto H, et al. Serum hepatitis C virus RNA quantity and histological features of hepatitis C virus carriers with persistently normal ALT levels. Hepatology 1994;19:871-5.
13. Sangiovanni A, Morales R, Spinzi G, Rumi M, Casiraghi A, Ceriani R, et al. Interferon alfa treatment of HCV RNA carriers with persistently normal transaminase levels: a pilot randomized controlled study. Hepatology 1998;27:853-6.
14. Hagiwara H, Hayashi N, Mita E, Ueda K, Takehara T, Kasahara A, et al. Detection of hepatitis C virus RNA in serum of patients with chronic hepatitis C treated with interferon-α. Hepatology 1992;15:37-41.
15. Mita E, Hayashi N, Hagiwara H, Ueda K, Kanazawa Y, Kasahara A, et al. Predicting interferon therapy efficacy from hepatitis C virus genotype and RNA liter. Dig Dis Sci 1994;39: 977-82.
16. Tsubota A, Chayama K, Ikeda K, Yasuji A, Koida I, Saitoh S, et al. Factors predictive of response to interferon-alpha therapy in hepatitis C virus infection. Hepatology 1994;19:1088-94.
17. Martinot-Peignoux M, Marcellin P, Pouteau M, Castelnau C, Boyer N, Poliquin M, et al. Pretreatment serum hepatitis C virus RNA levels and hepatitis C virus genotype are the main and independent prognostic factors of sustained response to interferon alfa therapy in chronic hepatitis C. Hepatology 1995;22: 1050-6.
18. Nousbaum JB, Pol S, Nalpas B, Landais P, Berthelot P, Brechot C. Hepatitis C virus type 1b (II) infection in France and Italy. Collaborative Study Group. Ann Intern Med 1995;122:161-8.
19. Kanazawa Y, Hayashi N, Mita E, Li T, Hagiwara H, Kasahara A, et al. Influence of viral quasispecies on effectiveness of interferon therapy in chronic hepatitis C patients. Hepatology 1994; 20:1121-30.
20. Enomoto N, Sakuma I, Asahina Y, Kurosaki M, Murakami T, Yamamoto C, et al. Comparison of full-length sequences of interferon-sensitive and resistant hepatitis C virus 1b. J Clin Invest 1995;96:224-30.
21. Enomoto N, Sakuma I, Asahina Y, Kurosaki M, Murakami T, Yamamoto C, et al. 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.
22. Orito E, Mizokami M, Suzuki K, Ohba K, Ohno T, Mori M, et al. Loss of serum HCV RNA at week 4 of interferon-alpha therapy is associated with more favorable long-term response in patients with chronic hepatitis C. J Med Virol 1995;46:109-15.
23. Kakumu S, Aiyama T, Okumura A, Iwata K, Ishikawa T, Yoshioka K. Earlier loss of hepatitis C virus RNA in interferon therapy can predict a long-term response in chronic hepatitis C. J Gastroenterol Hepatol 1997;12:468-72.
24. MuHutchison J, Blatt L, Sedghi-Vaziri A, Russell J, Schmid P, Conrad A. Is there an optimal time to measure quantitative HCV RNA to predict non-response following interferon treatment for chronic HCV infection? J Hepatol 1998;29:362-8.
25. Neumann AU, Lam NP, Dahari H, Gretch DR, Wiley TE, Layden TJ, et al. Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy. Science 1998;282: 103-7.
26. Zeuzem S, Schmidt JM, Lee JH, Ruster B, Roth WK. Effect of interferon alfa on the dynamics of hepatitis C virus turnover in vivo. Hepatology 1996;23:366-71.
27. Davis GL, Balart LA, Schiff ER, Lindsay K, Bodenheimer HC, Rerrilo RP, et al. Treatment of chronic hepatitis C with recombinant interferon alpha. A multicenter randomized controlled trial. N Engl J Med 1989;321:1501-6.
28. Di Bisceglie AM, Martin P, Kassianides C, Lisker-Melman M, Murray L, Waggoner J, et al. Recombinant interferon alpha therapy for chronic hepatitis C. A randomized, double-blind placebo-controlled trial. N Engl J Med 1989;321:1506-10.
29. Kasahara A, Hayashi N, Hiramatsu N, Oshita M, Hagiwara H, Katayama K, et al. Ability of prolonged interferon treatment to suppress relapse after cessation of therapy in patients with chronic hepatitis C: a multicenter randomized controlled trial. Hepatology 1995;21:291-7.
30. Hiramatsu N, Hayashi N, Kasahara A, Hagiwara H, Takehara T, Haruna Y, et al. Improvement of liver fibrosis in chronic hepatitis C patients treated with natural interferon alpha. J Hepatol 1995;22:135-42.
31. Carithers RL Jr, Emerson SS. Therapy of hepatitis C. Metaanalysis of interferon alfa-2b trials. Hepatology 1997;26:883-8.
32. Marcellin P, Boyer N, Giostra E, Degott C, Courouce AM, Degos F, et al. Recombinant human α-interferon in patients with chronic non-A, non-B hepatitis: a multicenter randomized controlled trial from France. Hepatology 1991;13:393-7.
33. Causse X, Godinot H, Chevallier M, Chossegros P, Zoulim Fouzan D, et al. Comparison of 1 or 3MU of interferon alfa-2b and placebo in patients with chronic non-A, non-B hepatitis. Gastroenterology 1991;101:497-502.
34. Poynard T, Leroy V, Cohard M, Thevenot T, Mathurin P, Opolon P, et al. Meta-analysis of interferon randomized trials in the treatment of viral hepatitis: effects of dose and duration. Hepatology 1996;24:778-89.
35. Chemello L, Cavaletto L, Casarin C, Bonetti P, Bernardinello E, Pontisso P, et al. Persistent hepatitis C viremia predicts late relapse after sustained response to interferon-α in chronic hepatitis C. Ann Intern Med 1996;124:1058-60.
36. Chemello L, Bonetti P, Cavalletto L, Talato F, Donadon V, Casarin P, et al. Randomized trial comparing three different regimens of alpha-2a-interferon in chronic hepatitis C. The TriVeneto Viral Hepatitis Group. Hepatology 1995;22:700-6.
37. Marcellin P, Pouteau M, Martinot-Peignoux M, Degos F, Duchatelle V, Boyer N, et al. Lack of benefit of escalating dosage of interferon alfa in patients with chronic hepatitis C. Gastroenterology 1995;109:156-65.
38. Lindsay KL, Davis GL, Schiff ER, Bodenheimer HC, Balart LA, Dienstag JL, et al. Response to higher doses of interferon alfa-2b in patients with chronic hepatitis C: a randomized multicenter trial. Hepatitis Interventional Therapy Group. Hepatology 1996; 24:1034-40.
39. 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: 1457-62.
40. Lin R, Roach E, Zimmerman M, Strasser S, Farrell GC. Interferon alfa-2b for chronic hepatitis C: effects of dose increment and duration of treatment on response rates. Results of the first multicenter Australian trial. Australia Hepatitis C Study Group. J Hepatol 1995;23:487-96.
41. Saracco G, Borghesio E, Mesina P, Solinas A, Spezia C, Macor F, et al. Prolonged treatment (2 years) with different doses (3 versus 6MU) of interferon alpha-2b for chronic hepatitis C. Results of a multicenter randomized trial. J Hepatol 1997;27:56-62.
42. Yoshioka K, Kakumu S, Wakita T, Ishikawa T, Itoh Y, Takayanagi M, et al. Detection of hepatitis C virus by polymerase chain reaction and response to interferon therapy: relationship to genotypes of hepatitis C virus. Hepatology 1992; 16:293-9.
43. Fukuda M, Chayama K, Tsubota A, Kobayashi M, Hashimoto M. Miyano Y, et al. Predictive factors in eradicating hepatitis C virus using a relatively small dose of interferon. J Gastroenterol Hepatol 1998;13:412-8.
44. Yuki N, Hayashi N, Kasahara A, Hagiwara H, Takehara T, Oshita M, et al. Pretreatment viral load and response to prolonged interferon-α course for chronic hepatitis C. J Hepatol 1995;22:457-63.
45. Kobayashi Y, Watanabe S, Konishi M, Yokoi M, Kakehashi R, Kaito M, et al. Quantitation and typing of serum hepatitis C virus RNA in patients with chronic hepatitis C treated with interferon-beta. Hepatology 1993;18:1319-25.
46. Kurosaki M, Enomoto N, Murakami T, Sakuma I, Asahina Y, Yamamoto C, et al. Analysis of genotypes and amino acid residues 2209-2248 of NS5A region of hepatitis C virus in relation to the response to interferon-beta therapy. Hepatology 1997;25:750-3.
47. Kasahara A, Hayashi N, Mochizuki K, Oshita M, Katayama K, Kato M, et al. Circulating matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 as serum markers of fibrosis in patients with chronic hepatitis C. Relationship to interferon response. J Hepatol 1997;26:574-83.
48. Furusho N, Hayashi J, Ohmiya M, Sawayama Y, Kawakami Y, Ariyama I, et al. Differences between interferon-alpha and -beta treatment for patients with chronic hepatitis C virus infection. Dig Dis Sci 1999;44:608-17.
49. Fujiwara K, Mochida S, Matsuo S, Ogata I, Hayashi S, Sato Y, Randomized control trial of interferon-beta injection at 12-b intervals as a therapy for chronic hepatitis C. Hepatol Res 1998;12:240-51.
50. Bellobuuono A, Mondazzi L, Tempini S, Chiodo F, Magliano E, Mondini C, et al. Should patients with early loss of serum HCV-RNA during alpha interferon therapy for chronic hepatitis C be treated with 6 or 12 months? J Hepatol 1999;30:8-13.
51. Camma C, Giunta M, Chemello L, Alberti A, Toyoda H, Trepo C. Chronic hepatitis C: interferon retreatment of relapsers. A meta-analysis of individual patient data. European Concerted Action on Viral Hepatitis (EUROHEP). Hepatology 1999;30: 801-7.
52. Di Bisceglie AM, Conjeevaram HS, Fried MW, Sallie R, Park Y, Yurdaydin C, et al. Ribavirin as therapy for chronic hepatitis C. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1995;123:897-903.
53. Dusheiko G, Main J, Thomas H, Reichard O, Lee C, Dhillon A, et al. Ribavirin treatment for patients with chronic hepatitis C: results of a placebo-controlled study. J Hepatol 1996;25:591-8.
54. Bodenheimer HC Jr, Lindsay KL, Davis GL, Lewis JH, Thung SN, Seeff LB. Tolerance and efficacy of oral ribavirin treatment of chronic hepatitis C: a multicenter trial. Hepatology 1997;26: 473-7.
55. Reichard O, Norkrans G, Fryden A, Braconier JH, Sonnerborg A, Weiland O. Randomized, double-blind, placebo-controlled trial of interferon alpha-2b with and without ribavirin for chronic hepatitis C. The Swedish Study Group. Lancet 1998;351:83-7.
56. Poynard T, Marcellin P, Lee SS, Niederau C, Minuk GS, Ideo G, et al. Randomized trial of interferon a 2b plus ribavirin for 48 weeks or for 24 weeks versus interferon a 2b plus placebo for 48 weeks of the treatment of chronic infection with hepatitis C virus. Lancet 1998;352:1426-32.
57. McHutchison JG, Gordon SC, Schiff ER, Shiffman ML, Lee WM, Rustgi VK, et al. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. N Engl J Med 1998;339:1485-92.
58. Davis GL, Esteban-Mur R, Rustgi V, Hoefs J, Gordon SC, Trepo C, et al. Interferon alfa-2b alone or in combination with ribavirin for the treatment of relapse of chronic hepatitis C. International Hepatitis Interventional Group. N Engl J Med 1998;339:1493-9.
59. Shindo M, Di-Bisceglie AM, Hoofnagle JH, Long-term follow-up of patients with chronic hepatitis C treated with alpha-interferon. Hepatology 1992;15:1013-6.
60. Saracco G, Rosina F, Abate ML, Chiandussi L, Gallo V, Cerutti E, et al. Long-term follow-up of patients with chronic hepatitis C treated with different doses of interferon-alpha 2b. Hepatology 1993;18:1300-5.
61. Castillo I, Bartolome J, Navas S, Gonzalez S, Herrero M, Carreno V. Virological and biochemical long-term follow-up of patients with chronic hepatitis C treated with interferon. Hepatology 1994;19:1342-6.
62. Lau JYN, Mizokami M, Ohno T, Diamond DA, Kniffen J, Davis GL. Discrepancy between biochemical and virological responses to interferon-α in chronic hepatitis C. Lancet 1993;342:1208-9.
63. Kasahara A, Hayashi N, Mochizuki K, Takayanagi M, Yoshioka K, Kakumu S, et al. Risk factors for hepatocellular carcinoma and its incidence after interferon treatment in patients with chronic hepatitis C. Hepatology 1998;27:1394-402.
64. Kanto T, Hayashi N, Takehara T, Hagiwara H, Mita E, Oshita M, et al. Serial density analysis of hepatitis C virus particle populations in chronic hepatitis C patients treated with interferon-alpha. J Med Virol 1995;46:230-7.
65. Omata M, Ito Y, Yokosuka O, Imazeki F, Uchiumi K, Takano S, et al. Histological changes of the liver by treatment of chronic non-A, non-B hepatitis with recombinant leukocyte interferon alpha. Dig Dis Sci 1989;34:330-7.
66. Knodell RG, Ishak KG, Black WC, Chen TS, Craig R, Kaplowitz N, et al. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1981;1:431-5.
67. Schvarcz R, Glaumann H, Weiland O, Norkans G, Wejstal R, Fryden A. Histological outcome in interferon alpha-2b treated patients with chronic posttransfusion non-A, non-B hepatitis. Liver 1991;11:30-8.
68. Manabe N, Chevallier M, Chossegros P, Causse X, Guerret S, Trepo C, et al. Interferon α-2b therapy reduces liver fibrosis in chronic non-A, non-B hepatitis: a quantitative histological evaluation. Hepatology 1993;18:1344-9.
69. Sobesky R, Mathurin P, Charlotte F, Moussalli J, Olivi M, Vidaud M, et al. Modeling the impact of interferon alfa treatment on liver fibrosis progression in chronic hepatitis C: a dynamic view. Gastroenterology 1999;116:378-86.
70. Lau DTL, Kleiner DE, Ghany MG, Park Y, Schmid P, Hoofnagle JH. Ten-year follow-up after interferon-α therapy for chronic hepatitis C. Hepatology 1998;28:1121-7.
71. Duchatelle V, Marcellin P, Giostra E, Bregeaud L, Pouteau M, Boyer N, et al. Changes in liver fibrosis at the end of alpha interferon therapy and 6 to 18 months later in patients with chronic hepatitis C: quantitative assessment by a morphometric method. J Hepatol 1998;29:20-8.
72. Marcellin P, Boyer N, Gervais A, Martinot M, Poteau M, Castelnau C, et al. Long-term histologic improvement and loss of detectable intrahepatic HCV RNA in patients with chronic hepatitis C and sustained response to interferon-α therapy. Ann Intern Med 1997;127:875-81.
73. Czaja MJ, Weiner FR, Flader KC, Giambrone M-A, Wind R, Biempica L, et al. In vitro and in vivo association of transforming growth factor-β 1 with hepatic fibrosis. J Cell Biol 1989;108: 2477-82.
74. Armendaniz-Borunda J, Seyer JM, Kang AH, Raghow R, Regulation of TGF β gene expression in rat liver intoxicated with carbon tetrachloride. FASEB J 1990;4:215-21.
75. Ignotz RA, Massague J. Tranforming growth factor-β stimulates the expression of fibronectin and collagen and their incorporation into extracellular matrix. J Biol Chem 1986;261:4337-45.
76. Roberts AB, Spoen MB, Associan RK, Smith JM, Roche NS, Wakefield LM, et al. Transforming growth factor type β: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci USA 1986;83: 4167-71.
77. Raghow R, Postlethwaite AE, Keski-Oja J, Moses HL, Kang AH. Transforming growth factor-β increases steady-state levels of type I procollagen and fibronectin messenger RNAs posttranscriptionally in cultured human dermal fibroblasts. J Clin Invest 1987;79:1285-8.
78. Edwards DR, Murphy G, Reynolds JJ, Whitham SE, Docherty AJ, Angel P, et al. Transforming growth factor β modulates the expression of collagenase and metalloproteinase inhibitor. EMBO J 1987;6:1899-904.
79. Sanderson N, Factor V, Nagy P, Kopp J, Kondaiah P, Wakefield L, et al. Hepatic expression of transforming growth factor-β 1 in transgenic mice results in multiple tisse lesions. Proc Natl Acad Sci USA 1995;92:2572-6.
80. Castilla A, Prieto J, Fausto N. Transforming growth factor β 1 and a in chronic liver disease: effects of interferon alfa therapy. N Engl J Med 1991;324:933-40.
81. Tsushima H, Kawata S, Tamura S, Ito N, Shirai Y, Kiso S, et al. Reduced plasma transforming growth-factor-β 1 levels in patients with chronic hepatitis C after interferon-α therapy: association with regression of hepatic fibrosis. J Hepatol 1999;30: 1-7.
82. Sakaida I, Nagatomi A, Hironaka K, Uchida K, Okita K. Quantitative analysis of liver fibrosis and stellate cell changes in patients with chronic hepatitis C after interferon therapy. Am J Gastroenterol 1999;94:489-96.
83. Imai Y, Kawata S, Tamura S, Yabuuchi I, Noda S, Inada M, et al. Relation of interferon therapy and hepatocellular carcinoma in patients with chronic hepatitis C. Ann Intern Med 1998;129:94-9.
84. Ikeda K, Saitoh S, Arase Y, Chayama K, Suzuki Y, Kobayashi M, et al. Effect of interferon therapy on hepatocellular carcinogenesis in patients with chronic hepatitis C: a long-term observation study of 1643 patients using statistical bias correction with proportional hazard analysis. Hepatology 1999;29: 1124-30.
85. Yoshida H, Shiratori Y, Moriyama M, Arakawa Y, Ide T, Sata M, et al. Interferon therapy reduces the risk for hepatocellular carcinoma: national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan. Ann Intern Med 1999;131:174-81.
86. Nishiguchi S, Kuroki T, Nakatani S, Moriomoto H, Takeda T, Nakajima S, et al. Randomized trial of effects of interferon-alpha on incidence of hepatocellular carcinoma in chronic active hepatitis C with cirrhosis. Lancet 1995;346:1051-5.
87. Valla DC, Chevallier M, Marcellin P, Payen JL, Trepo C, Fonck M, et al. Treatment of hepatitis C virus-related cirrhosis: a randomized, controlled trial of interferon alfa-2b versus no treatment. Hepatology 1999;29:1870-5.
88. Mazzella G, Accogli E, Sottili S, Festi D, Orsini M, Salzetta A, et al. Alpha interferon treatment may prevent hepatocellular carcinoma in HCV-relaled liver cirrhosis. J Hepatol 1996;24:141-7.
89. Fattovich G, Giustina G, Degos F, Diodati G, Tremolada F, Nevens F, et al. Effectiveness of interferon alfa on incidence of hepatocellular carcinoma and decompensation in cirrhosis type C. European Concerted Action on Viral Hepatitis. J Hepatol 1997;27:201-5.
90. Brunetto MR, Oliveri F, Koehler M, Zahm F, Bonino F, (International Interferon-α Hepatocellular Carcinoma Study Group). Effect of interferon-alpha on progression of cirrhosis to hepatocellular carcinoma: a retrospective cohort study. Lancet 1998;351:1535-9.
91. Serfaty L, Aumaitre H, Chazouilleres O, Bonnand AM, Rosmorduc O, Poupon RE, et al. Determinants of outcome of compensated hepatitis C virus-related cirrhosis. Hepatology 1998;27:1435-40.
92. Benvegnu L, Chemello L, Noventa F, Fattovich G, Pontisso P, Alberti A. Retrospective analysis of the effect of interferon therapy on the clinical outcome of patients with viral cirrhosis. Cancer 1998;83:901-9.
93. Okanoue T, Itoh Y, Minami M, Sakamoto S, Yasui K, Sakamoto M, et al. Interferon therapy lowers the rate of progression to hepatocellular carcinoma in chronic hepatitis C but not significantly in advanced stage: a retrospective study in 1148 patients. J Hepatol 1999;30:653-9.
94. Shindo M, Ken A, Okuno T. Varying incidence of cirrhosis and hepatocellular carcinoma in patients with chronic hepatitis C responding differently to interferon therapy. Cancer 1999;85: 1943-50.
95. Tarao K, Takemiya S, Tamai S, Sugimasa Y, Ohkawa S, Akaike M, et al. Relationship between the recurrence of hepatocellular carcinoma (HCC) and serum alanine aminotransferase levels in hepatectomized patients with hepatitis C virus-associated cirrhosis and HCC. Cancer 1997;79:688-94.
96. Arase Y, Ikeda K, Murashima N, Chayama K, Tsubota A, Koida I, et al. The long-term efficacy of glycyrrhizin in chronic hepatitis C patients. Cancer 1997;79:1494-500.
97. Takano S, Ito Y, Yokosuka O, Ohto M, Uchiumi K, Hirota K, et al. A multicenter randomized controlled dose study of ursodeoxycholic acid for chronic hepatitis C. Hepatology 1994;20:558-64.
98. Angelico M, Gandin C, Pescarmona E, Rapicetta M, Del Vecchio, Bini A, et al. Recombinant interferon-alpha and ursodeoxycholic acid versus interferon-alpha alone in the treatment of chronic hepatitis C: a randomized clinical trial with long-term follow-up. Am J Gastroenterol 1995;90:263-9.
99. Tanaka K, Kondo M, Sakaguchi T, Saito S, Arata S, Ikeda M, et al. Efficacy of ursodeoxycholic acid in combination with interferon-α in treating chronic hepatitis C: results of a long-term follow-up trial. J Gastroenterol Hepatol 1996;11:1155-60.
100. Weinberg E, Weinberg G. The role of iron in infection. Curr Opin Infect Dis 1995;8:164-9.
101. Bonkovsky HL, Banner BF, Rothman AL. Iron and chronic viral hepatitis. Hepatology 1997;25:759-68.
102. Firianati F, Cardin R, De Maria N, Libera CD, Marafin C, Lecis E, et al. Iron storage, lipid peroxidation and glutathione turnover in chronic anti-HCV positive patients. J Hepatol 1995;22: 449-56.
103. Van Thiel DH, Friedlander L, Fagiuoli S, Wright HI, Irish W, Gavaler JS. Response to interferon α therapy is influenced by the iron content of the liver. J Hepatol 1994;20:410-5.
104. Bonkovsky HL. Therapy of hepatitis C: other options. Hepatology 1997;26:1438-515.
105. Hayashi H, Takikawa T, Nishimura N, Yano M, Isomura T, Sakamoto N. Improvement of serum aminotransferase levels after phlebotomy in patients with chronic active hepatitis C and excess hepatic iron. Am J Gastroenterol 1994;89:986-8.
106. Fong T-L, Han SH, Tsai NCS, Morgan TR, Mizokami M, Qian D, et al. A pilot randomized, controlled trial of the effect of iron depletion on long-term response to α-interferon in patients with chronic hepatitis C. J Hepatol 1998;28:369-74.
107. Guyader D, Boucher E, Andre P, Even C, Cottereau J, Bianchi A, et al. A pilot study of iron depletion as adjuvant therapy in chronic hepatitis C patients not responding to interferon. Am J Gastroenterol 1999;94:1696-9.
108. Oka Y, Yamamoto S, Kuroki T, Harihara S, Marumo T, Kim SR, et al. Prospective study of chemoprevention of hepatocellular carcinoma with Sho-saiko-to (TJ-9). Cancer 1995;76: 743-9.
109. Sakaida I, Matsumura Y, Akiyama S, Hayashi K, Ishige A, Okita K. Herbal medicine Sho-saiko-to (TJ-9) prevents liver fibrosis and enzyme-altered lesions in rat liver cirrhosis induced by a choline-deficient L-amino acid-deficient diet. J Hepatol 1998;28: 298-306.
110. Shimizu I, Ma YR, Mizobuchi Y, Liu F, Miura T, Nakai Y, et al. Effects of Sho-saiko-to, a Japanese herbal medicine, on hepatic fibrosis in rats. Hepatology 1999;29:149-60.