Kurzfassung der aktualisierten S3-Leitlinie „Diagnostik und Therapie der Hepatitis B”

Zusammenfassung

Die Behandlungsoptionen der Hepatitis B Virusinfektionen haben sich in den letzten Jahren stark erweitert. Weiterhin haben neue Erkenntnisse zum natürlichen Verlauf der Hepatitis B eine Anpassung der Leitlinien erforderlich gemacht. Das Kompetenznetz Hepatitis hat daher in Kooperation mit der Deutschen Gesellschaft für Verdauungs- und Stoffwechselkrankheiten e. V. (DGVS), der Deutschen Gesellschaft für Pathologie e. V. (DGP), der Gesellschaft für Virologie (GfV) und der Deutschen Gesellschaft für Pädiatrische Gastroenterologie und Ernährung (DPGE) die S3 Leitlinien zur Hepatitis B von 2003 überarbeitet. Wichtige Neuerungen betreffen die Bedeutung der Indikationsstellung zu einer antiviralen Therapie, wobei eine HBV-Viruslast von 104 Kopien/ml (2000 IU/ml) als kritische Grenze angesehen wird. Weiterhin werden klare Empfehlungen zur Vermeidung und Behandlung von Resistenzen gegen Nukleos(ti)analoga gegeben. Eigene Kapitel beschäftigen sich mit der Bedeutung von HBV im Kontext von Organtransplantation und Koinfektionen, der Therapie von Kindern und der Prophylaxe einer HBV Infektion.

Summary

Therapeutic option for hepatitis B virus infection have significantly improved in recent years. Moreover, new insights in the natural history of hepatitis B required an update of current national guidelines. Therefore, the German network of competence on viral hepatitis (Hep-Net) has revised guidelines on diagnosis and treatment og HBV incetion in cooperation with the national societies for Gastroenterology, Pathology, Virology, and Pediatric Gastroenterology. Important alterations concern the indication for antiviral therapy considering an HBV viremia of 104 copies/ml (2000 IU/ml) as a critical level. Moreover, specific recommendations how to prevent and to treat antiviral drug resistance are given. Finally, the importance of HBV in the context of organ and bone marrow transplantation, treatment of coinfections and children and prophylaxis of HBV is covered.

Schlüsselwörter

Hepatitis B - Leitlinien

Key words

hepatitis B - guidelines

Literatur

• 1 Ballauff A, Schneider T, Gerner P, Habermehl P, Behrens R, Wirth S. Safety and efficacy of interferon retreatment in children with chronic hepatitis B.  Eur J Pediatr. 1998;  157 382-385
• 2 Bodsworth N J, Cooper D A, Donovan B. The influence of human immunodeficiency virus type 1 infection on the development of the hepatitis B virus carrier state.  J Infect Dis. 1991;  163 1138-1140
• 3 Chang T T, Gish R G, de Man R, Gadano A, Sollano J, Chao Y C, Lok A S, Han K H, Goodman Z, Zhu J, Cross A, DeHertogh D, Wilber R, Colonno R, Apelian D. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B.  N Engl J Med. 2006;  354 1001-1010
• 4 Chen C J, Yang H I, Su J, Jen C L, You S L, Lu S N, Huang G T, Iloeje U H. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level.  JAMA. 2006;  295 65-73
• 5 Colonno R J, Rose R E, Pokornowski K, Baldick C J, Klesczewski K, Tenney D. Assessment at three years shows high barrier to resistance is maintained in entecavir-treated nucleoside naïve patients while resistance emergence increases over time in lamivudine refractory patients.  Hepatology. 2006;  44 229A-230A
• 6 Colonno R J, Rose R, Baldick C J, Levine S, Pokornowski K, Yu C F, Walsh A, Fang J, Hsu M, Mazzucco C, Eggers B, Zhang S, Plym M, Klesczewski K, Tenney D J. Entecavir resistance is rare in nucleoside naive patients with hepatitis B.  Hepatology. 2006;  44 1656-1665
• 7 Cornberg M, Protzer U, Dollinger M M, Petersen J, Wedemeyer H, Berg T, Jilg W, Erhardt A, Wirth S, Schirmacher P, Fleig W E, Manns M P. Prophylaxis, Diagnosis and Therapy of Hepatitis-B-Virus-(HBV-)Infection: upgrade of the guideline, AWMF-Register 021/011.  Z Gastroenterol. 2007;  45 525-574
• 8 Dienstag J L, Schiff E R, Wright T L, Perrillo R P, Hann H W, Goodman Z, Crowther L, Condreay L D, Woessner M, Rubin M, Brown N A. Lamivudine as initial treatment for chronic hepatitis B in the United States.  N Engl J Med. 1999;  341 1256-1263
• 9 Fattovich G, Boscaro S, Noventa F, Pornaro E, Stenico D, Alberti A, Ruol A, Realdi G. Influence of hepatitis delta virus infection on progression to cirrhosis in chronic hepatitis type B.  J Infect Dis. 1987;  155 931-935
• 10 Hadziyannis S J, Papatheodoridis G V, Dimou E, Laras A, Papaioannou C. Efficacy of long-term lamivudine monotherapy in patients with hepatitis B e antigen-negative chronic hepatitis B.  Hepatology. 2000;  32 847-851
• 11 Hadziyannis S J, Tassopoulos N C, Heathcote E J, Chang T T, Kitis G, Rizzetto M, Marcellin P, Lim S G, Goodman Z, Wulfsohn M S, Xiong S, Fry J, Brosgart C L. Adefovir dipivoxil for the treatment of hepatitis B e antigen-negative chronic hepatitis B.  N Engl J Med. 2003;  348 800-807
• 12 Hadziyannis S J, Tassopoulos N C, Heathcote E J, Chang T T, Kitis G, Rizzetto M, Marcellin P, Lim S G, Goodman Z, Ma J, Brosgart C L, Borroto-Esoda K, Arterburn S, Chuck S L. Long-term Therapy With Adefovir Dipivoxil for HBeAg-Negative Chronic Hepatitis B for up to 5 Years.  Gastroenterology. 2006;  131 1743-1751
• 13 Hadziyannis S J, Tassopoulos N C, Heathcote E J, Chang T T, Kitis G, Rizzetto M, Marcellin P, Lim S G, Goodman Z, Ma J, Arterburn S, Xiong S, Currie G, Brosgart C L. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B.  N Engl J Med. 2005;  352 2673-2681
• 14 Hadziyannis S J, Sevastianos V, Rapti I, Tassopoulos N. Sustained biochemical and virological remission after discontinuation of 4 to 5 years of adefovir dipivoxil treatment in HBeAg-negative chronic hepatitis B.  Hepatology. 2006;  44 231A
• 15 Jardi R, Rodriguez F, Buti M, Costa X, Cotrina M, Galimany R, Esteban R, Guardia J. 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. 2001;  34 404-410
• 16 Jonas M M, Mizerski J, Badia I B, Areias J A, Schwarz K B, Little N R, Greensmith M J, Gardner S D, Bell M S, Sokal E M. Clinical trial of lamivudine in children with chronic hepatitis B.  N Engl J Med. 2002;  346 1706-1713
• 17 Lai C L, Shouval D, Lok A S, Chang T T, Cheinquer H, Goodman Z, DeHertogh D, Wilber R, Zink R C, Cross A, Colonno R, Fernandes L. Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B.  N Engl J Med. 2006;  354 1011-1020
• 18 Lai C L, Gane E, Hsu C W, Thongsawat S, Wang Y, Chen Y, Heathcote E J, Rasenack J, Bzowej N, Naoumov N, Zeuzem S, Di Bisceglie A, Chao G C, Fielman Constance B A, Brown N A. Two-year results from the GLOBE trial in patients with hepatitis B: greater clinical and antiviral efficacy for telbivudine vs lamivudine.  Hepatology. 2006;  44 222A
• 19 Lai C L, Gane E, Liaw Y F, Thongsawat S, Wang Y M, Chen Y G, Heathcote E J, Rasenack J, Bzowej N, Naoumov N, Chao G, Constance B F, Brown N A. Telbivudine (LdT) vs. lamivudine for chronic hepatitis B: First-year results from the international phase III globe trial.  Hepatology. 2005;  42 748A
• 20 Lai C L, Dienstag J, Schiff E, Leung N W, Atkins M, Hunt C, Brown N, Woessner M, Boehme R, Condreay L. Prevalence and clinical correlates of YMDD variants during lamivudine therapy for patients with chronic hepatitis B.  Clin Infect Dis. 2003;  36 687-696
• 21 Lai C L, Chien R N, Leung N W, Chang T T, Guan R, Tai D I, Ng K Y, Wu P C, Dent J C, Barber J, Stephenson S L, Gray D F. Asia Hepatitis Lamivudine Study Group . A one-year trial of lamivudine for chronic hepatitis B.  N Engl J Med. 1998;  339 61-68
• 22 Lau G K, Piratvisuth T, Luo K X, Marcellin P, Thongsawat S, Cooksley G, Gane E, Fried M W, Chow W C, Paik S W, Chang W Y, Berg T, Flisiak R, McCloud P, Pluck N. Peginterferon Alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B.  N Engl J Med. 2005;  352 2682-2695
• 23 Lee Y S, Suh D J, Lim Y S, Jung S W, Kim K M, Lee H C, Chung Y H, Lee Y S, Yoo W, Kim S O. Increased risk of adefovir resistance in patients with lamivudine-resistant chronic hepatitis B after 48 weeks of adefovir dipivoxil monotherapy.  Hepatology. 2006;  43 1385-1391
• 24 Liaw Y F, Leung N W, Chang T T, Guan R, Tai D I, Ng K Y, Chien R N, Dent J, Roman L, Edmundson S, Lai C L. Asia Hepatitis Lamivudine Study Group . Effects of extended lamivudine therapy in Asian patients with chronic hepatitis B.  Gastroenterology. 2000;  119 172-180
• 25 Lok A S, Lai C L, Leung N, Yao G B, Cui Z Y, Schiff E R, Dienstag J L, Heathcote E J, Little N R, Griffiths D A, Gardner S D, Castiglia M. Long-term safety of lamivudine treatment in patients with chronic hepatitis B.  Gastroenterology. 2003;  125 1714-1722
• 26 Manns M P, Wedemeyer H, Meyer S, Roggendorf M, Niederau C, Blum H E, Jilg W, Fleig W E. Diagnosis, progression and therapy of hepatitis-B-virus infection - results of an evidenced based consensus conference of the German Society for Alimentary Metabolic Disorders and and in cooperation with the Hepatitis Competence Network.  Z Gastroenterol. 2004;  42 677-678
• 27 Marcellin P, Lau G K, Bonino F, Farci P, Hadziyannis S, Jin R, Lu Z M, Piratvisuth T, Germanidis G, Yurdaydin C, Diago M, Gurel S, Lai M Y, Button P, Pluck N. Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B.  N Engl J Med. 2004;  351 1206-1217
• 28 Marcellin P, Chang T T, Lim S G, Tong M J, Sievert W, Shiffman M L, Jeffers L, Goodman Z, Wulfsohn M S, Xiong S, Fry J, Brosgart C L. Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B.  N Engl J Med. 2003;  348 808-816
• 29 Mathurin P, Thibault V, Kadidja K, Ganne-Carrie N, Moussalli J, El Younsi M, Di M, Lunel V F, Charlotte F, Vidaud M, Opolon P, Poynard T. Replication status and histological features of patients with triple (B, C, D) and dual (B, C) hepatic infections.  J Viral Hepat. 2000;  7 15-22
• 30 Ranger-Rogez S, Alain S, Denis F. Hepatitis viruses: mother to child transmission.  Pathol Biol (Paris). 2002;  50 568-575
• 31 Rizzetto M. Hepatitis delta: the virus and the disease.  J Hepatol. 1990;  11 (Suppl 1) S145-S148
• 32 Samuel D, Forns X, Berenguer M, Trautwein C, Burroughs A, Rizzetto M, Trepo C. Report of the monothematic EASL conference on liver transplantation for viral hepatitis (Paris, France, January 12 - 14, 2006).  J Hepatol. 2006;  45 127-143
• 33 Sherman M, Yurdaydin C, Sollano J, Silva M, Liaw Y F, Cianciara J, Boron-Kaczmarska A, Martin P, Goodman Z, Colonno R, Cross A, Denisky G, Kreter B, Hindes R. Entecavir for treatment of lamivudine-refractory, HBeAg-positive chronic hepatitis B.  Gastroenterology. 2006;  130 2039-2049
• 34 Smedile A, Farci P, Verme G, Caredda F, Cargnel A, Caporaso N, Dentico P, Trepo C, Opolon P, Gimson A, Vergani D, Williams R, Rizzetto M. Influence of delta infection on severity of hepatitis B.  Lancet. 1982;  2 945-947
• 35 Weltman M D, Brotodihardjo A, Crewe E B, Farrell G C, Bilous M, Grierson J M, Liddle C. Coinfection with hepatitis B and C or B, C and delta viruses results in severe chronic liver disease and responds poorly to interferon-alpha treatment.  J Viral Hepat. 1995;  2 39-45
• 36 Westland C E, Yang H, Delaney W E, Gibbs C S, Miller M D, Wulfsohn M, Fry J, Brosgart C L, Xiong S. Week 48 resistance surveillance in two phase 3 clinical studies of adefovir dipivoxil for chronic hepatitis B.  Hepatology. 2003;  38 96-103
• 37 Yurdaydin C, Wedemeyer H, Zachou K, Erhardt A, Cakaloglu Y, Degertekin H, Gurel S, Zeuzem S, Daleoso G, Bozkaya H, Dienes H P, Bock T, Manns M P. A multicenter randomised study comparing the efficacy of pegylated interferon-alfa-2a plus adefovir dipivoxil vs. pegylated interferon-alfa-2a plus placebo vs. adefovir dipivoxil for the treatment of chronic delta hepatitis.  Hepatology. 2006;  44 230A