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DOI: 10.1055/s-0028-1109984
© Georg Thieme Verlag KG Stuttgart · New York
Retrospective Analysis of Chronic Hepatitis D in a West German University Clinic over Two Decades: Migratory Pattern, Prevalence and Clinical Outcome
Retrospektive Analyse der chronischen Hepatitis D an einer westdeutschen Universitätsklinik über 2 Dekaden: zunehmende Migrationsmuster, Prävalenz und klinischer VerlaufPublication History
manuscript received: 27.9.2009
manuscript accepted: 7.12.2009
Publication Date:
04 August 2010 (online)

Zusammenfassung
Hintergrund: Epidemiologie, klinische Aspekte und Langzeitverlauf der chronischen Hepatitis D wurden in einem nicht endemischen zentraleuropäischen Gebiet untersucht. Methoden: Unter 1307 HBsAg-Trägern, die sich am Universitätsklinikum Düsseldorf vorstellten, wurden innerhalb von 2 Dekaden (1989 – 2008) 67 Patienten mit chronischer Hepatitis D identifiziert und über 7 ± 6 Jahre beobachtet. Eine Interferontherapie über mindestens 6 Monate erhielten 41 Patienten. Ergebnisse: Die Prävalenz der Hepatitis D stieg unter den HBsAg-Trägern innerhalb von 2 Dekaden von 4,1 auf 6,2 % an (p < 0,06). Die Anzahl der Patienten aus der früheren Sowjetunion (32,1 vs. 46,2 %) und Afrika (0 vs. 17,9 %) nahm zu, aus dem Mittelmeerraum ab (46,5 vs. 17,9 % p < 0,03). Der Zeitraum zwischen der Diagnose der Hepatitis B und D betrug 4,8 ± 7 Jahre (p < 0,0001). Eine anhaltende Virussuppression nach IFN-Therapie wurde bei 19,5 % der Patienten erzielt. Die jährliche Inzidenz für Tod, HCC und Komplikationen betrug 3,2, 2,7 und 8 % bei Patienten mit Leberzirrhose. Das Gesamt- und komplikationsfreie Überleben über 12 Jahre lag bei 72 und 45 % für Patienten mit Zirrhose im Vergleich zu 100 % für Patienten ohne Zirrhose (p < 0,008 und p < 0,0001). Schlussfolgerung: Migrationshintergrund und der mögliche Anstieg der Hepatitis D im Westen Deutschlands sollten im klinischen Alltag berücksichtigt werden. Langzeitverlauf und Ansprechen auf Interferon sind ähnlich schlecht wie in endemischen Gebieten, sodass die frühzeitige Diagnosestellung verbessert werden sollte.
Abstract
Background/Aims: Epidemiology, clinical features and long term-course of chronic hepatitis D were addressed in a non-endemic Central European area. Methods: Sixty-seven patients with chronic hepatitis D were identified among 1307 HBsAg carriers at the university hospital Düsseldorf during two decades (1989 – 2008) and followed for a mean of 7 ± 6 years. Forty-one of these were treated with IFN-alfa for at least six months. Results: Hepatitis D prevalence increased from 4.1 to 6.2 % among HBsAg carriers during the two decades (p < 0.06). Patients originating from the former Soviet Union (32.1 vs. 46.2 %) and Africa (0 vs. 17.9 %) became more frequent whereas the prevalence of patients from Southern Europe declined (46.5 vs.17.9 % p < 0.03). The time span between the diagnosis of hepatitis B and D was 4.8 ± 7 years (p < 0.0001). A sustained virological response to interferon-alfa was achieved in 19.5 % of the patients. The yearly incidence rates for death, HCC and complications were 3.2 %, 2.7 % and 8 % among patients with liver cirrhosis. Estimated survival and complication-free survival during 12 years were 72 % and 45 % in cirrhotic compared to 100 % in non-cirrhotic patients (p < 0.008 and p < 0.0001, respectively). Conclusion: Hepatitis D in western Germany appears to be on the increase and has a migration background that should be considered in clinical practice. Clinical outcome and response to IFN are as poor as in endemic regions, indicating the need to improve early diagnosis.
Schlüsselwörter
Hepatitis D - Interferon - Zirrhose
Key words
hepatitis D - interferon - cirrhosis
References
- 1 Rizzetto M. Hepatitis D: thirty years after. J Hepatol. 2009; 50 1043-1050
- 2 Farci P. Delta hepatitis: an update. J Hepatol. 2003; 39 (Suppl 1) S212-S219
- 3 Erhardt A, Knuth R, Sagir A. et al . Socioepidemiological data on hepatitis delta in a German university clinic – increase in patients from Eastern Europe and the former Soviet Union. Z Gastroenterol. 2003; 41 523-526
- 4 Flodgren E, Bengtsson S, Knutsson M. et al . Recent high incidence of fulminant hepatitis in Samara, Russia: molecular analysis of prevailing hepatitis B and D virus strains. J Clin Microbiol. 2000; 38 3311-3316
- 5 Gaeta G B, Stroffolini T, Chiaramonte M. et al . Chronic hepatitis D: a vanishing disease? An Italian multicenter study. Hepatology. 2000; 32 824-827
- 6 Rosina F, Conoscitore P, Cuppone R. et al . Changing pattern of chronic hepatitis D in Southern Europe. Gastroenterology. 1999; 117 161-166
- 7 Sagnelli E, Stroffolini T, Ascione A. et al . The epidemiology of hepatitis delta infection in Italy. Promoting Group. J Hepatol. 1992; 15 211-215
- 8 Hadziyannis S J, Dourakis S P, Papaioannou C. et al . Changing epidemiology and spreading modalities of hepatitis delta virus infection in Greece. Prog Clin Biol Res. 1993; 382 259-266
- 9 Degertekin H, Yalcin K, Yakut M. et al . Seropositivity for delta hepatitis in patients with chronic hepatitis B and liver cirrhosis in Turkey: a meta-analysis. Liver Int. 2008; 28 494-498
- 10 Fattovich G, Boscaro S, Noventa F. et al . Influence of hepatitis delta virus infection on progression to cirrhosis in chronic hepatitis type B. J Infect Dis. 1987; 155 931-935
- 11 Fattovich G, Giustina G, Christensen E. et al . Influence of hepatitis delta virus infection on morbidity and mortality in compensated cirrhosis type B. The European Concerted Action on Viral Hepatitis (Eurohep). Gut. 2000; 46 420-426
- 12 Niro G A, Ciancio A, Gaeta G B. et al . Pegylated interferon alpha-2b as monotherapy or in combination with ribavirin in chronic hepatitis delta. Hepatology. 2006; 44 713-720
- 13 Niro G A, Rosina F, Rizzetto M. Treatment of hepatitis D. J Viral Hepat. 2005; 12 2-9
- 14 Erhardt A, Gerlich W, Starke C. et al . Treatment of chronic hepatitis delta with pegylated interferon-alpha2b. Liver Int. 2006; 26 805-810
- 15 Castelnau C, Le Gal F, Ripault M P. et al . Efficacy of peginterferon alpha-2b in chronic hepatitis delta: relevance of quantitative RT-PCR for follow-up. Hepatology. 2006; 44 728-735
- 16 Gunsar F, Akarca U S, Ersoz G. et al . Two-year interferon therapy with or without ribavirin in chronic delta hepatitis. Antivir Ther. 2005; 10 721-726
- 17 Kaymakoglu S, Karaca C, Demir K. et al . Alpha interferon and ribavirin combination therapy of chronic hepatitis D. Antimicrob Agents Chemother. 2005; 49 1135-1138
- 18 Rizzetto M, Verme G, Recchia S. et al . Chronic hepatitis in carriers of hepatitis B surface antigen, with intrahepatic expression of the delta antigen. An active and progressive disease unresponsive to immunosuppressive treatment. Ann Intern Med. 1983; 98 437-441
- 19 Saracco G, Rosina F, Brunetto M R. et al . Rapidly progressive HBsAg-positive hepatitis in Italy. The role of hepatitis delta virus infection. J Hepatol. 1987; 5 274-281
- 20 Verme G, Brunetto M R, Oliveri F. et al . Role of hepatitis delta virus infection in hepatocellular carcinoma. Dig Dis Sci. 1991; 36 1134-1136
- 21 Desmet V J, Gerber M, Hoofnagle J H. et al . Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology. 1994; 19 1513-1520
- 22 Le Gal F, Castelnau C, Gault E. et al . Hepatitis D virus infection – not a vanishing disease in Europe. Hepatology. 2007; 45 1332-1333
- 23 Cross T J, Rizzi P, Horner M. et al . The increasing prevalence of hepatitis delta virus (HDV) infection in South London. J Med Virol. 2008; 80 277-282
- 24 Wedemeyer H, Heidrich B, Manns M P. Hepatitis D virus infection – not a vanishing disease in Europe. Hepatology. 2007; 45 1331-1332, author reply 1332 – 1333
- 25 Kalinin A L, Zhavoronok S V, Mikhailov M I. et al . Viral hepatitis delta in the republic of Belarus. Zh Mikrobiol Epidemiol Immunobiol. 1998; 6 74-77
- 26 Trautwein C, Kiral G, Tillmann H L. et al . Risk factors and prevalence of hepatitis E in German immigrants from the former Soviet Union. J Med Virol. 1995; 45 429-434
- 27 Romeo R, Del Ninno E, Rumi M. et al . A 28-year study of the course of hepatitis Delta infection: a risk factor for cirrhosis and hepatocellular carcinoma. Gastroenterology. 2009; 136 1629-1638
- 28 Colombo M, Cambieri R, Rumi M G. et al . Long-term delta superinfection in hepatitis B surface antigen carriers and its relationship to the course of chronic hepatitis. Gastroenterology. 1983; 85 235-239
- 29 Smedile A, Farci P, Verme G. et al . Influence of delta infection on severity of hepatitis B. Lancet. 1982; 2 945-947
- 30 Pugnale P, Pazienza V, Guilloux K. et al . Hepatitis delta virus inhibits alpha interferon signaling. Hepatology. 2009; 49 398-406
- 31 Lau D T, Kleiner D E, Park Y. et al . Resolution of chronic delta hepatitis after 12 years of interferon alfa therapy. Gastroenterology. 1999; 117 1229-1233
- 32 Rodriguez-Torres M, Jeffers L J, Sheikh M Y. et al . Peginterferon alfa-2a and ribavirin in Latino and non-Latino whites with hepatitis C. N Engl J Med. 2009; 360 257-267
- 33 Muir A J, Bornstein J D, Killenberg P G. Peginterferon alfa-2b and ribavirin for the treatment of chronic hepatitis C in blacks and non-Hispanic whites. N Engl J Med. 2004; 350 2265-2271
Prof. Dr. Andreas Erhardt
Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum der Heinrich-Heine-Universität Düsseldorf
Moorenstr. 5
40225 Düsseldorf
Germany
Phone: ++ 49/2 11/8 11 82 68
Fax: ++ 49/2 11/8 11 81 32
Email: erhardt@med.uni-duesseldorf.de