Hepatitis in the clinics — Treatment options

  • Michael P. Manns
  • Katja Deterding
Part of the Birkhäuser Advances in Infectious Diseases book series (BAID)


Hepatitis is an inflammation of the liver based on different aetiologies. Clinicians distinguish acute from chronic hepatitis. Pathophysiological changes lead to damage and hepatocellular degeneration. The causes for hepatocellular injury are heterogeneous, such as viruses, toxins, drugs, autoimmunity, cryptogenic. The latest official classification of chronic hepatitis by the International Association the Study of the Liver (IASL) [1] is still valid and is based on:
  1. 1.


  2. 2.

    Inflammatory activity (Grading)

  3. 3.

    Fibrosis stage (Staging)


This classification has become very relevant since we nowadays not only diagnose the different liver diseases according to their aetiology but also have developed specific treatments that are targeting specific aetiologies of chronic liver disease. Overlap syndromes with primary biliary cirrhosis and primary sclerosing cholangitis and genetic liver diseases add to the clinical spectrum of this syndrome.

In this chapter we will describe the different causes of hepatitis, their treatment options and differential diagnosis.


Liver Disease Chronic Hepatitis Hepatic Encephalopathy Primary Biliary Cirrhosis Primary SCLEROSING Cholangitis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Desmet VJ, Gerber M, Hoofnagle JH, Manns M, Scheuer PJ (1994) Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology 19: 1513–1520PubMedGoogle Scholar
  2. 2.
    Diepolder HM (2004) [Prevention and therapy of viral hepatitis]. Internist (Berl) 45: 197–209CrossRefGoogle Scholar
  3. 3.
    Feinstone SM, Kapikian AZ, Purceli RH (1973) Hepatitis A: detection by immune electron microscopy of a virus like antigen associated with acute illness. Science 182: 1026–1028PubMedCrossRefGoogle Scholar
  4. 4.
    Hadem J (2003) Immunopathogenesis and treatment of hepatitis A. In: ME Gershwin, JM Vierling, MP Manns (eds) In: Liver immunology. Hanley and Belfus Inc, Philadelphia 185–201Google Scholar
  5. 5.
    Lemon SM (2000) Hepatitis A virus. Update on viral hepatitis. Textbook for the annual meeting of the American Association for the study of Liver DiseasesGoogle Scholar
  6. 6.
    Ostapowicz G, Fontana RJ, Schiodt FV, Larson A, Davern TJ, Han SH, McCashland TM, Shakil AO, Hay JE, Hynan L et al (2002) Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med 137: 947–954PubMedGoogle Scholar
  7. 7.
    Acharya SK, Dasarathy S, Kumer TL, Sushma S, Prasanna KS, Tandon A, Sreenivas V, Nijhawan S, Panda SK, Nanda SK et al (1996) Fulminant hepatitis in a tropical population: clinical course, cause, and early predictors of outcome. Hepatology 23: 1448–1455PubMedCrossRefGoogle Scholar
  8. 8.
    Bernuau J, Rueff B, Benhamou JP (1986) Fulminant and subfulminant liver failure: definitions and causes. Semin Liver Dis 6: 97–106PubMedGoogle Scholar
  9. 9.
    Cornberg M, Protzer U, Dollinger MM, Petersen J, Wedemeyer H, Berg T, Jilg W, Erhardt A, Wirth S, Schirmacher P et al (2007) [Prophylaxis, diagnosis and therapy of hepatitis-B-virus-(HBV-) infection: upgrade of the guideline, AWMF-Register 021/011]. Z Gastroenterol 45: 525–574PubMedCrossRefGoogle Scholar
  10. 10.
    Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH (2006) Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 295: 65–73PubMedCrossRefGoogle Scholar
  11. 11.
    Cooksley WG, Piratvisuth T, Lee SD, Mahachai V, Chao YC, Tanwandee T, Chutaputti A, Chang WY, Zahm FE, Pluck N (2003) Peginterferon alpha-2a (40 kDa): an advance in the treatment of hepatitis B e antigen-positive chronic hepatitis B. J Viral Hepat 10: 298–305PubMedCrossRefGoogle Scholar
  12. 12.
    Alberti A, Boccato S, Vario A, Benvegnu L (2002) Therapy of acute hepatitis C. Hepatology 36: S195–S200PubMedCrossRefGoogle Scholar
  13. 13.
    Wiegand J, Buggisch P, Boecher W, Zeuzem S, Gelbmann CM, Berg T, Kauffmann W, Kallinowski B, Cornberg M, Jaeckel E et al (2006) Early monotherapy with pegylated interferon alpha-2b for acute hepatitis C infection: the HEP-NET acute-HCV-II study. Hepatology 43: 250–256PubMedCrossRefGoogle Scholar
  14. 14.
    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: 958–965PubMedCrossRefGoogle Scholar
  15. 15.
    Cornberg M, Wedemeyer H, Manns MP (2002) Treatment of chronic hepatitis C with PEGylated interferon and ribavirin. Curr Gastroenterol Rep 4: 23–30PubMedCrossRefGoogle Scholar
  16. 16.
    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: 975–982PubMedCrossRefGoogle Scholar
  17. 17.
    Hadziyannis SJ, Sette H Jr, Morgan TR, Balan V, Diago M, Marcellin P, Ramadori G, Bodenheimer H Jr, Bernstein D, Rizzetto M et al (2004) Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med 140: 346–355PubMedGoogle Scholar
  18. 18.
    Manns MP, Foster GR, Rockstroh JK, Zeuzem S, Zoulim F, Houghton M (2007) The way forward in HCV treatment-finding the right path. Nat Rev Drug Discov 6: 991–1000PubMedCrossRefGoogle Scholar
  19. 19.
    Manns MP, Wedemeyer H, Cornberg M (2006) Treating viral hepatitis C: efficacy, side effects, and complications. Gut 55: 1350–1359PubMedCrossRefGoogle Scholar
  20. 20.
    Rizzetto M (1989) Hepatitis delta virus (HDV) infection and disease. Ric Clin Lab 19: 11–26PubMedGoogle Scholar
  21. 21.
    Niro GA, Rosina F, Rizzetto M (2005) Treatment of hepatitis D. J Viral Hepat 12: 2–9PubMedCrossRefGoogle Scholar
  22. 22.
    Jardi R, Rodriguez F, Buti M, Costa X, Cotrina M, Galimany R, Esteban R, Guardia J (2001) Role of hepatitis B, C, and D viruses in dual and triple infection: influence of viral genotypes and hepatitis B precore and basal core promoter mutations on viral replicative interference. Hepatology 34: 404–410PubMedCrossRefGoogle Scholar
  23. 23.
    Wedemeyer H, Yurdaydin C, Dalekos G, Erhardt A, Cakaloglu Y, Degertekin H, Gurel S, Zeuzem S, Bock T, Zachou K et al (2007) 72 week data of the HIDIT-1 Trial: A multicenter randomised study comparing PEG-Interferonalpha-2a plus adefovir vs. PEG-Interferon-alpha-2a plus placebo vs. adefovir in chronic delta hepatitis. J Hepatology 46: S4CrossRefGoogle Scholar
  24. 24.
    Gupta DN, Smetana HF (1957) The histopathology of viral hepatitis as seen in the Delhi epidemic (1955–1956). Indian J Med Res 45: 101–113PubMedGoogle Scholar
  25. 25.
    Khuroo MS (1980) Chronic liver disease after non-A, non-B hepatitis. Lancet 2: 860–861PubMedGoogle Scholar
  26. 26.
    Boberg KM, Aadland E, Jahnsen J, Raknerud N, Stiris M, Bell H (1998) Incidence and prevalence of primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis in a Norwegian population. Scand J Gastroenterol 33: 99–103PubMedCrossRefGoogle Scholar
  27. 27.
    Alvarez F, Berg PA, Bianchi FB, Bianchi L, Burroughs AK, Cancado EL, Chapman RW, Cooksley WG, Czaja AJ, Desmet VJ et al (1999) International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol 31: 929–938PubMedCrossRefGoogle Scholar
  28. 28.
    Vergani D, Alvarez F, Bianchi FB, Cancado EL, Mackay IR, Manns MP, Nishioka M, Penner E (2004) Liver autoimmune serology: a consensus statement from the committee for autoimmune serology of the International Autoimmune Hepatitis Group. J Hepatol 41: 677–683PubMedCrossRefGoogle Scholar
  29. 29.
    Manns MP, Griffin KJ, Sullivan KF, Johnson EF (1991) LKM-1 autoantibodies recognize a short linear sequence in P450IID6, a cytochrome P-450 monooxygenase. J Clin Invest 88: 1370–1378PubMedCrossRefGoogle Scholar
  30. 30.
    Strassburg CP, Alex B, Zindy F, Gerken G, Luttig B, Meyer zum Buschenfelde KH, Brechot C, Manns MP (1996) Identification of cyclin A as a molecular target of antinuclear antibodies (ANA) in hepatic and non-hepatic autoimmune diseases. J Hepatol 25: 859–866PubMedCrossRefGoogle Scholar
  31. 31.
    Manns M, Gerken G, Kyriatsoulis A, Staritz M, Meyer zum Buschenfelde KH (1987) Characterisation of a new subgroup of autoimmune chronic active hepatitis by autoantibodies against a soluble liver antigen. Lancet 1: 292–294PubMedCrossRefGoogle Scholar
  32. 32.
    Wies I, Brunner S, Henninger J, Herkel J, Kanzler S, Meyer zum Buschenfelde KH, Lohse AW (2000). Identification of target antigen for SLA/LP autoantibodies in autoimmune hepatitis. Lancet 355: 1510–1515PubMedCrossRefGoogle Scholar
  33. 33.
    Vergani D, Alvarez F, Bianchi FB, Cancado EL, Mackay IR, Manns MP, Nishioka M, Penner E (2004) Liver autoimmune serology: a consensus statement from the committee for autoimmune serology of the International Autoimmune Hepatitis Group. J Hepatol 41: 677–683PubMedCrossRefGoogle Scholar
  34. 34.
    Nikias GA, Batts KP, Czaja AJ (1994) The nature and prognostic implications of autoimmune hepatitis with an acute presentation. J Hepatol 21: 866–871PubMedCrossRefGoogle Scholar
  35. 35.
    Kirk AP, Jain S, Pocock S, Thomas HC, Sherlock S (1980) Late results of the Royal Free Hospital prospective controlled trial of prednisolone therapy in hepatitis B surface antigen negative chronic active hepatitis. Gut 21: 78–83PubMedCrossRefGoogle Scholar
  36. 36.
    Read AE, Sherlock S, Harrison CV (1963) Active ‘juvenile’ cirrhosis considered as part of a systemic disease and the effect of corticosteroid therapy. Gut 4: 378–393PubMedCrossRefGoogle Scholar
  37. 37.
    Czaja AJ (1996) The variant forms of autoimmune hepatitis. Ann Intern Med 125: 588–598PubMedGoogle Scholar
  38. 38.
    van Buuren HR, van Hoogstraten HJE, Terkivatan T, Schalm SW, Vleggaar FP (2000) High prevalence of autoimmune hepatitis among patients with primary sclerosing cholangitis. J Hepatol 33: 543–548PubMedCrossRefGoogle Scholar
  39. 39.
    Yoon Y-H, Yi Hy, Smothers Ba (2004) Liver cirrhosis martality in the United states 1970–2001. NIAAA Surveillance report #67Google Scholar
  40. 40.
    Becker U, Deis A, Sorensen TI, Gronbaek M, Borch-Johnsen K, Muller CF, Schnohr P, Jensen G (1996) Prediction of risk of liver disease by alcohol intake, sex, and age: a prospective population study. Hepatology 23: 1025–1029PubMedCrossRefGoogle Scholar
  41. 41.
    MacSween RN, Burt AD (1986) Histologic spectrum of alcoholic liver disease. Semin Liver Dis 6: 221–232PubMedCrossRefGoogle Scholar
  42. 42.
    D’Amico G, Pagliaro L, Bosch J (1995) The treatment of portal hypertension: a meta analytic review. Hepatology 22: 332–354PubMedCrossRefGoogle Scholar
  43. 43.
    Boyer TD, Wright TL, Manns MP (2006) Zakim and Boyer’s hepatology — a textbook of liver disease, 5th edition, Saunders ElsevierGoogle Scholar
  44. 44.
    Gines P, Quintero E, Arroyo V, Teres J, Bruguera M, Rimola A, Caballeria J, Rodes J, Rozman C (1987) Compensated cirrhosis: natural history and prognostic factors. Hepatology 7: 122–128PubMedCrossRefGoogle Scholar
  45. 45.
    O’Grady JG, Schalm SW, Williams R (1993) Acute liver failure: redefining the syndromes. Lancet 342: 273–275PubMedCrossRefGoogle Scholar
  46. 46.
    Mahl TC, Shockcor W, Boyer JL (1994) Primary biliary cirrhosis: survival of a large cohort of symptomatic and asymptomatic patients followed for 24 years. J Hepatol 20: 707–713PubMedCrossRefGoogle Scholar
  47. 47.
    Sherlock S, Scheuer PJ (1973) The presentation and diagnosis of 100 patients with primary biliary cirrhosis. N Engl J Med 289: 674–678PubMedGoogle Scholar
  48. 48.
    Kim WR, Lindor KD, Locke GR III, Therneau TM, Homburger HA, Batts KP, Yawn BP, Petz JL, Melton LJ III, Dickson ER (2000) Epidemiology and natural history of primary biliary cirrhosis in a US community. Gastroenterology 119: 1631–1636PubMedCrossRefGoogle Scholar
  49. 49.
    Shibata M, Onozuka Y, Morizane T, Koizumi H, Kawaguchi N, Miyakawa H, Kako M, Mitamura K (2004) Prevalence of antimitochondrial antibody in Japanese corporate workers in Kanagawa prefecture. J Gastroenterol 39: 255–259PubMedCrossRefGoogle Scholar
  50. 50.
    Talwalkar JA, Lindor KD (2003) Primary biliary cirrhosis. Lancet 362: 53–61PubMedCrossRefGoogle Scholar
  51. 51.
    Angulo P, Lindor KD (1999) Primary sclerosing cholangitis. Hepatology 30: 325–332PubMedCrossRefGoogle Scholar
  52. 52.
    Chapman RW (2003) The management of primary sclerosing cholangitis. Curr Gastroenterol Rep 5: 9–17PubMedCrossRefGoogle Scholar
  53. 53.
    Aadland E, Schrumpf E, Fausa O, Elgjo K, Heilo A, Aakhus T, Gjone E (1987) Primary sclerosing cholangitis: a long-term follow-up study. Scand J Gastroenterol 22: 655–664PubMedCrossRefGoogle Scholar
  54. 54.
    Quigley EM, LaRusso NF, Ludwig J, MacSween RN, Birnie GG, Watkinson G (1983) Familial occurrence of primary sclerosing cholangitis and ulcerative colitis. Gastroenterology 85: 1160–1165PubMedGoogle Scholar
  55. 55.
    Wanless IR, Lentz JS (1990) Fatty liver hepatitis (steatohepatitis) and obesity: an autopsy study with analysis of risk factors. Hepatology 12: 1106–1110PubMedCrossRefGoogle Scholar
  56. 56.
    Dixon JB, Bhathal PS, O’Brien PE (2001) Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese. Gastroenterology 121: 91–100PubMedCrossRefGoogle Scholar
  57. 57.
    Pagano G, Pacini G, Musso G, Gambino R, Mecca F, Depetris N, Cassader M, David E, Cavallo-Perin P, Rizzetto M (2002) Nonalcoholic steatohepatitis, insulin resistance, and metabolic syndrome: further evidence for an etiologic association. Hepatology 35: 367–372PubMedCrossRefGoogle Scholar
  58. 58.
    Ruhl CE, Everhart JE (2003) Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the United States. Gastroenterology 124: 71–79PubMedCrossRefGoogle Scholar
  59. 59.
    Diehl AM, Goodman Z, Ishak KG (1988) Alcohollike liver disease in nonalcoholics. A clinical and histologic comparison with alcohol-induced liver injury. Gastroenterology 95: 1056–1062PubMedGoogle Scholar
  60. 60.
    Merryweather-Clarke AT, Pointon JJ, Shearman JD, Robson KJ (1997) Global prevalence of putative haemochromatosis mutations. J Med Genet 34: 275–278PubMedGoogle Scholar
  61. 61.
    Feder JN, Gnirke A, Thomas W, Tsuchihashi Z, Ruddy DA, Basava A, Dormishian F, Domingo R Jr, Ellis MC, Fullan A et al (1996) A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet 13: 399–408PubMedCrossRefGoogle Scholar
  62. 62.
    Niederau C, Fischer R, Purschel A, Stremmel W, Haussinger D, Strohmeyer G (1996) Long-term survival in patients with hereditary hemochromatosis. Gastroenterology 110: 1107–1119PubMedCrossRefGoogle Scholar
  63. 63.
    Adams PC, Kertesz AE, Valberg LS (1993) Rate of iron reaccumulation following iron depletion in hereditary hemochromatosis. Implications for venesection therapy. J Clin Gastroenterol 16: 207–210PubMedCrossRefGoogle Scholar
  64. 64.
    Carrell RW, Lomas DA (2002) Alpha1-antitrypsin deficiency-a model for conformational diseases. N Engl J Med 346: 45–53PubMedCrossRefGoogle Scholar
  65. 65.
    Sifers RN, Finegold MJ, Woo SL (1992) Molecular biology and genetics of alpha 1-antitrypsin deficiency. Semin Liver Dis 12: 301–310PubMedGoogle Scholar
  66. 66.
    Lomas DA, Evans DL, Finch JT, Carrell RW (1992) The mechanism of Z alpha 1-antitrypsin accumulation in the liver. Nature 357: 605–607PubMedCrossRefGoogle Scholar
  67. 67.
    Maier-Dobersberger T, Ferenci P, Polli C, Balac P, Dienes HP, Kaserer K, Datz C, Vogel W, Gangl A (1997) Detection of the His1069Gln mutation in Wilson disease by rapid polymerase chain reaction. Ann Intern Med 127: 21–26PubMedGoogle Scholar
  68. 68.
    Firneisz G, Lakatos PL, Szalay F, Polli C, Glant TT, Ferenci P (2002) Common mutations of ATP7B in Wilson disease patients from Hungary. Am J Med Genet 108: 23–28PubMedCrossRefGoogle Scholar
  69. 69.
    Hoogenraad TU (1998) Zinc treatment of Wilson’s disease. J Lab Clin Med 132: 240–241PubMedCrossRefGoogle Scholar

Copyright information

© Birkhäuser Verlag Basel/Switzerland 2008

Authors and Affiliations

  • Michael P. Manns
    • 1
  • Katja Deterding
    • 1
  1. 1.Department of Gastroenterology, Hepatology and EndocrinologyHannover Medical SchoolHannoverGermany

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