Abstract
Among the different types of viral infections affecting the liver, hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis delta virus (HDV) represent the major pathogens currently shown to cause chronic hepatitis. This condition implies persistence of viral infection and secondary inflammation for more than six months after initial exposure. Autoimmune hepatitis is a self-perpetuating hepatocellular inflammation characterized by specific histologic lesions and liver-associated auto-antibodies. Alcoholic hepatitis is a frequent condition in the Western world, due to excessive alcohol consumption and progressing to cirrhosis, especially in subjects who continue to abuse ethanol. This chapter focuses on current therapeutic options and novel strategies for the treatment of these conditions.
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References
Lok AS, McMahon BJ (2001) Chronic hepatitis B. Hepatology 34: 1225–1241
Liaw YF (2002) Therapy of chronic hepatitis B: Current challenges and opportunities. JViral Hepat 9: 393–399
Perry CM, Wagstaff AJ (1998) Interferon-a-nl: A review of its pharmacological prop-erties and therapeutic efficacy in the management of chronic viral hepatitis. Biodrugs 9: 125–154
Mallat A, Preaux AM, Blazejewski S, Rosenbaum J, Dhumeaux D, Mavier P (1995) Interferon alfa and gamma inhibit proliferation and collagen synthesis of human Ito cells in culture. Hepatology 21: 1003–1010
Wong DK, Cheung AM, O’Rourke K, Naylor CD, Detsky AS, Heathcote J (1993) Effect of alpha-interferon treatment in patients with hepatitis B e antigen-positive chronic hepatitis B. A meta-analysis. Ann Intern Med 119: 312–323
Niederau C, Heintges T, Lange S, Goldmann G, Niederau CM, Mohr L, Häussinger D (1996) Long-term follow-up of HBeAg-positive patients treated with interferon alfa for chronic hepatitis B. N Engl J Med 334: 1422–1427
Pramoolsinsup C (2002) Management of viral hepatitis B. J Gastroenterol Hepatol 17 (Suppi): S126–S146
Jarvis B, Faulds D (1999) Lamivudine. A review of its therapeutic potential in chronic hepatitis B. Drugs 58: 101–141
Noble S, Goa KL (1999) Adefovir dipivoxil. Drugs 58: 479–487
Yang H, Westland CE, Delaney IV WE, Heathcote EJ, Ho V, Fry J, Brosgart C, Gibbs CS, Miller MD, Xiong S (2002) Resistance surveillance in chronic hepatitis B patients treated with adefovir dipivoxil for up to 60 weeks. Hepatology 36: 464–473
McClellan MB (2002) New drug for hepatitis B. JAMA 288: 2112
Chan HL, Tang JL, Tam W, Sung JJY (2001) The efficacy of thymosin in the treatment of chronic hepatitis B virus infection: a meta-analysis. Aliment Pharmacol Ther 15: 1899–1905
Heathcote J, McHutchison J, Lee S, Tong M, Benner K, Minuk G, Wright T, Fikes J, Livingston B, Sette A et al (1999) A pilot study of the CY-1899 T-cell vaccine in subjects chronically infected with hepatitis B virus. Hepatology 30: 531–536
Galun E, Eren R, Safadi R, Ashour Y, Terrault N, Keeffe EB, Matot E, Mizrachi S, Terkieltaub D, Zohar M et al (2002) Clinical evaluation (Phase I) of a combination of two human monoclonal antibodies to HBV: Safety and antiviral properties. Hepatology 35: 673–679
Artillo S, Pastore G, Alberti A, Milella M, Santantonio T, Fattovich G, Giustina G, Ryff JC, Chaneac M, Bartolomé J et al (1998) Double-blind, randomized controlled trial of interleukin-2 treatment of chronic hepatitis B. J Med Virol 54: 167–172
Zeuzem S, Carreno V (2001) Interleukin-12 in the treatment of chronic hepatitis B and C. Antiviral Res 52: 181–188
von Weizsacker F, Wieland S, Kock J, Offensperger WB, Offensperger S, Moradpour D, Blum HE (1997) Gene therapy for chronic viral hepatitis: Ribozymes, antisense oligonucleotides, and dominant negative mutants. Hepatology 26: 251–255
Rivkina A, Rybalov S (2002) Chronic hepatitis B: Current and future treatment options. Pharmacotherapy 22: 721–737
Ying C, De Clercq E, Nicholson W, Furman P, Neyts J (2000) Inhibition of the replication of the DNA polymerase M550V mutation variant of human hepatitis B virus by adefovir, tenofovir, L-FMAU, DAPD, penciclovir and lobucavir. J Viral Hepat 7: 161–165
van Bömmel F, Wünske T, Schürmann D, Berg T (2002) Tenofovir treatment in patients with lamivudine-resistant hepatitis B mutants strongly affects viral replication. Hepatology 36: 507–508
Hadziyannis SJ (1999) Hepatitis D. Clin Liver Dis 3: 309–319
Yalcin K, Degertekin H, Yildiz F, Akkus Z (2002) A 12-month course of combination therapy with interferon-alfa and lamivudine in patients with chronic hepatitis delta virus: a single-center, prospective, open-label, uncontrolled study. Curr Ther Res Clin Exp 63: 736–747
Beccarello A, Bortolato L, Triches C, Paleari C, Awasum MC, Zalunardo B, Orlando R, Lirussi F (2002) Monoethylglycinexylidide kinetics and galactose elimination capacity during treatment with interferon-alfa for hepatitis C virus infection: Possible predictors of response? Curr Ther Res Clin Exp 63: 772–785
Lirussi F, Beccarello A, Castiglione G, Guglietta A (2002) Impaired natural killer cell cytotoxic activity in chronic hepatitis C viral infection: A single-center, controlled study. Curr Ther Res Clin Exp 63: 748–758
Lau JY, Tam RC, Liang TJ, Hong Z (2002) Mechanism of action of ribavirin in the combination treatment of chronic HCV infection. Hepatology 35: 1002–1009
Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, Koury K, Ling M, Albrecht JK (2001) Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: A randomised trial. Lancet 358: 958–965
Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL Jr, Haussinger D, Diago M, Carosi G, Dhumeaux D et al (2002) Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 347: 975–982
Khurshudian AV (2003) A pilot study to test the efficacy of oral administration of interferon-alpha lozenges to patients with Sjogren’s syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 95: 38–44
Osborn BL, Olsen HS, Nardelli B, Murray JH, Zhou JX, Garcia A, Moody G, Zaritskaya LS, Sung C (2003) Pharmacokinetic and pharmacodynamic studies of a human serum albumin-interferon-alpha fusion protein in cynomolgus monkeys. J Pharmacol Exp Ther 303: 540–548
Watson J (2002) Prospects for hepatitis C virus therapeutics: Levovirin and viramidine as improved derivatives of ribavirin. Curr Opin Investig Drugs 3: 680–683
McHutchison JG, Patel K (2002) Future therapy of hepatitis C. Hepatology 36 (Suppl 1): S245–S252
Firpi RJ, Nelson DR, Davis GL (2003) Lack of antiviral effect of a short course of mycophenolate mofetil in patients with chronic hepatitis C virus infection. Liver Transpl 9: 57–61
Lurie Y, Nevens F, Aprosina ZG, Fedorova TA, Kalinin AV, Klimova EA, Ilan Y, Maevskaya MV, Warnes TW, Yuschuk ND et al (2002) A multicentre, randomized study to evaluate the safety and efficacy of histamine dihydrochloride and interferon-alpha-2b for the treatment of chronic hepatitis C. J Viral Hepat 9: 346–353
Pockros PJ (2002) Developments in treatment of chronic hepatitis C. Expert Opin Invest Drugs 11: 1–14
Nelson DR, Lauwers GY, Lau JY, Davis GL (2000) Interleukin 10 treatment reduces fibrosis in patients with chronic hepatitis C: A pilot trial of interferon non-responders. Gastroenterology 118: 655–660
Frese M, Schwarzle V, Barth K, Krieger N, Lohmann V, Mihm S, Haller O, Bartenschlager R (2002) Interferon-gamma inhibits replicaton of subgenomic and genomic hepatitis C virus RNAs. Hepatology 35: 694–703
Lirussi F, Beccarello A, Bortolato L, Morselli-Labate AM, Crovatto M, Ceselli S, Santini G, Crepaldi G (1999) Long-term treatment of chronic hepatitis C with ursodeoxycholic acid: Influence of HCV genotypes and severity of liver disease. Liver 19: 381–388
Czaja AJ, Freese DK (2002) Diagnosis and treatment of autoimmune hepatitis. Hepatology 36: 479–497
Vergani D, Choudhuri K, Bogdanos DP, Mieli-Vergani G (2002) Pathogenesis of autoimmune hepatitis. Clin Liver Dis 6: 727–737
Soloway RD, Summerskill WH, Baggenstoss AH, Geall MG, Gitnick GL, Elveback LR, Schoenfield LJ (1972) Clinical, biochemical, and histological remission of severe chronic active liver disease: A controlled study of treatments and early prognosis. Gastroenterology 63: 820–833
Summerskill WH, Korman MG, Ammon HV, Baggenstoss AH (1975) Prednisone for chronic active liver disease: dose titration, standard dose, and combination with azathioprine compared. Gut 16: 876–883
Heneghan MA, McFarlane IG (2002) Current and novel immunosuppressive therapy for autoimmune hepatitis. Hepatology 35: 7–13
Vierling JM, Flores PA (2002) Evolving new therapies of autoimmune hepatitis. Clin Liver Dis 6: 825–850
Czaja AJ (2002) Treatment of autoimmune hepatitis. Seminar Liver Dis 22 (4): 365–378
Danielsson A, Prytz H (1994) Oral budesonide for treatment of autoimmune chronic active hepatitis. Aliment Pharmacol Ther 8: 585–590
Czaja AJ, Lindor KD (2000) Failure of budesonide in a pilot study of treatment-dependent autoimmune hepatitis. Gastroenterology 119: 1312–1316
Rebollo Bernardez J, Cifuentos Mimoso C, Pinar Moreno A, Caunedo Alvarez A, Salas Herrero E, Jiminez-Saenz M, Herrerias Gutierrez J (1999) Deflazacort for long-term maintenance of remission in type 1 autoimmune hepatitis. Rev Esp Enferm Dig 91: 630–638
Czaja AJ (2002) Treatment strategies in autoimmune hepatitis. Clin Liver Dis 6: 799–824
Pratt DS, Flavin DP, Kaplan MM (1996) The successful treatment of autoimmune hepatitis with 6-mercaptopurine after failure with azathioprine. Gastroenterology 110: 271–274
Malekzadeh R, Nasseri-Moghaddam S, Kaviani MJ, Taheri H, Kamalian N, Sotoudeh M (2001) Cyclosporin A is a promising alternative to corticosteroids in autoimmune hepatitis. Dig Dis Sci 46: 1321–1327
van Thiel DH, Wright H, Carroll P, Abu-Elmagd K, Rodriguez-Rilo H, McMichael J, Irish W, Starzl TE (1995) Tacrolimus: A potential new treatment for autoimmune chron-ic active hepatitis: Results of an open-label preliminary trial. Am J Gastroenterol 90: 771–776
Richardson PD, James PD, Ryder SD (2000) Mycophenolate mofetil for maintenance of remission in autoimmune hepatitis in patients resistant to or intolerant of azathioprine. J Hepatol 33: 371–375
Kanzler S, Gerken G, Dienes HP, Meyer zum Buschenfelde KH, Lohse AW (1997) Cyclophosphamide as alternative immunosuppressive therapy for autoimmune hepatitis — Report of three cases. Z Gastroenterol 35: 571–578
Burak KW, Urbanski SJ, Swain MG (1998) Successful treatment of refractory type 1 autoimmune hepatitis with methotrexate. J Hepatol 29: 990–993
Stern RB, Wilkinson SP, Howorth PJ, Williams R (1977) Controlled trial of synthetic Dpenicillamine and prednisone in maintenance therapy for active chronic hepatitis. Gut 18: 19–22
McClements BM, Callender ME (1990) D-penicillamine therapy in patients with HBsAg-negative chronic active hepatitis and major prednisolone-induced adverse effects. J Hepatol 11: 322–325
Lirussi F, Okolicsanyi L (1992) Cytoprotection with ursodeoxycholic acid: Effect in chronic non-cholestatic and chronic cholestatic liver disease. Ital J Gastroenterol 24: 31–35
Calmus Y, Gane P, Rouger P, Poupon R (1990) Hepatic expression of class I and class II major histocompatibility complex molecules in primary biliary cirrhosis: Effect of ursodeoxycholic acid. Hepatology 11: 12–15
Nakamura K, Yoneda M, Yokohama S, Tamori K, Sato Y, Aso K, Aoshima M, Hasegawa T, Makino I (1998) Efficacy of ursodeoxycholic acid in Japanese patients with type 1 autoimmune hepatitis. J Gastroenterol Hepatol 13: 490–495
Czaja AJ, Carpenter HA, Lindor KD (1999) Ursodeoxycholic acid as adjunctive therapy for problematic type 1 autoimmune hepatitis: A randomized placebo-controlled treatment trial. Hepatology 30: 1381–1386
Fulton S, McCullough AJ (1998) Treatment of alcoholic hepatitis. Clin Liver Dis 2: 799–819
Imperiale TF, McCullough AJ (1990) Do corticosteroids reduce mortality from alcoholic hepatitis? A meta-analysis of the randomized trials. Ann Intern Med 113: 299–307
McCullough AJ, O’Connor JF (1998) Alcoholic liver disease: Proposed recommendations for the American college of gastroenterology. Am J Gastroenterol 93: 2022–2036.
Christensen E, Gluud C (1995) Glucocorticoids are ineffective in alcoholic hepatitis: A meta-analysis adjusting for confounding variables. Gut 37: 113–118
Mathurin P, Duchatelle V, Ramond MJ, Degott C, Bedossa P, Erlinger S, Benhamou JP, Chaput JC, Ruett B, Poynard T (1996). Survival and prognostic factors in patients with severe alcoholic hepatitis treated with prednisolone. Gastroenterology 110: 1847–1853
Marchesini G, Bianchi G, Fabbri A (1998) Long-term management of alcoholic liver disease. Clin Liver Dis 2: 821–838
CabrĂ© E, RodrĂguez-Iglesias P, CaballerĂa J, Quer JC, Sánchez-Lombrana JL, ParĂ©s A, Papo M, Planas R, Gassull MA (2000) Short-and long-term outcome of severe alcohol-induced hepatitis treated with steroids or enteral nutrition: A multicenter randomized trial. Hepatology 32: 36–42
Colell A, Garcia-Ruiz C, Miranda M, Ardite E, Mari M, Morales A, Corrales F, Kaplowitz N, Fernandez-Checa JC (1998) Selective glutathione depletion of mitochondria by ethanol sensitizes hepatocytes to tumor necrosis factor. Gastroenterology 115: 1541–1551
Kono H, Rusyn I, Yin M, Gabele E, Yamashina S, Dikalova A, Kadiiska MB, Connor HD, Mason RP, Segal BH, et al (2000) NADPH oxidase-derived free radicals are key oxidants in alcohol-induced liver disease. J Clin Invest 106: 867–872
Akriviadis E, Botla R, Briggs W, Han S, Reynolds T, Shakil 0 (2000) Pentoxifylline improves short-term survival in severe acute alcoholic hepatitis: A double-blind, placebo-controlled trial. Gastroenterology 119: 1637–1648
Maher JJ (2002) Treatment of alcoholic hepatitis. J Gastroenterol Hepatol 17: 448–455
Rambaldi A, Gluud C (2001) Meta-analysis of propylthiouracil for alcoholic liver disease — A Cochrane hepato-biliary group review. Liver 21: 398–404
Sogni P, Hadengue A, Moreau R, Le moine 0, Soupison T, Oberti F, Farinotti R, Lebrec D (1997) Acute effects of propylthiouracil on hemodynamics and oxygen content in patients with alcoholic cirrhosis. J Hepatol 26: 628–633
Ross AD, Dey I, Janes N, Israel Y (1998) Effect of antithyroid drugs on hydroxyl radical formation and alpha-1-proteinase inhibitor inactivation by neutrophils: Therapeutic implications. J Pharmacol Exp Ther 285: 1233–1238
Mato JM, Camara J, Fernandez de Paz J, CaballerĂa L, Coll S, Caballero A, Garcia-Buey L, Beltran J, Benita V, CaballerĂa J et al (1999) S-adenosylmethionine in alcoholic liver cirrhosis: A randomized, placebo-controlled, double-blind, multicenter clinical trial. J Hepatol 30: 1081–1089
Ferenci P, Dragosics B, Dittrich H, Frank H, Benda L, Lochs H, Meryn S, Base W, Schneider B (1989) Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J Hepatol 9: 105–113
ParĂ©s A, Planas R, Torres M, CaballerĂa J, Viver JM, Acero D, PanĂ©s J, Rigau J, Santos J, RodĂ©s J (1998) Effects of silymarin in alcoholic patients with cirrhosis of the liver: Results of a controlled, double-blind, randomized and multicenter trial. J Hepatol 28: 615–621
Kershenobich D, Vargas F, Garcia-Tsao G, Perez Tamayo R, Gent M, Rojkind M (1988) Colchicine in the treatment of cirrhosis of the liver. N Engl J Med 318: 1709–1713
Rambaldi A, Gluud C (2001) Colchicine for alcoholic and non-alcoholic liver fibrosis or cirrhosis. Liver 21: 129–136
Cortez-Pinto H, Alexandrino P, Camilo ME, Gouveia-Oliveira A, Santos PM, Alves MM, Moura MC (2002) Lack of effect of colchicine in alcoholic cirrhosis: Final results of a double blind randomized trial. Eur J Gastroenterol Hepatol 14: 377–381
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Lirussi, F., Zalunardo, B. (2004). Current and future therapy of chronic hepatitis. In: Guglietta, A. (eds) Pharmacotherapy of Gastrointestinal Inflammation. Progress in Inflammation Research. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-7930-9_3
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DOI: https://doi.org/10.1007/978-3-0348-7930-9_3
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