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Z Gastroenterol 2016; 54(12): 1306-1311
DOI: 10.1055/s-0042-120418
Originalarbeit
© Georg Thieme Verlag KG Stuttgart · New York

Treatment of fulminant acute Hepatitis B with nucles(t)id analogues is safe and does not lead to secondary chronification of Hepatitis B

Therapie der akuten fulminanten Hepatitis B mit Nucleos(t)id-Analogen ist sicher und führt nicht zur Chronifizierung der Hepatitis B
C. Jochum
1   Gastroenterology and Hepatology, University Hospital Essen, Germany
,
F. Maischack
1   Gastroenterology and Hepatology, University Hospital Essen, Germany
,
O. E. Anastasiou
1   Gastroenterology and Hepatology, University Hospital Essen, Germany
,
J. Verheyen
2   Institute for Virology, University Hospital Essen, Germany
,
J. Timm
3   Institut für Virologie, Universitatsklinikum Dusseldorf, Germany
,
L. Bechmann
1   Gastroenterology and Hepatology, University Hospital Essen, Germany
,
G. Gerken
1   Gastroenterology and Hepatology, University Hospital Essen, Germany
,
A. Canbay
1   Gastroenterology and Hepatology, University Hospital Essen, Germany
› Author Affiliations
Further Information

Publication History

06 August 2016

04 November 2016

Publication Date:
09 December 2016 (online)

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Abstract

Background: Acute hepatitis B virus (HBV) infection is still a major cause of acute liver failure (ALF), necessitating a high rate of emergency liver transplantation (LTx). Acute infection is followed by high viral replication rates leading to hepatocyte death and, ultimately, ALF. The objective of treating HBV-induced ALF thus is to eliminate, or significantly suppress, HBV replication and therefore reduce cell death and support regeneration.

Objective: In this retrospective study, we want to evaluate the timing, the safety, and the long-term virological outcome of this approach.

Methods/results: In this study, we included 32 patients (16 female and 16 males; median age 39.5 years) with ALF due to hepatitis B, who were transferred to the university hospital Essen, Germany between January 2009 and December 2013. Before treatment, transaminases were highly elevated, bilirubin was increased, and elevated international normalized ratio (INR) revealed impaired liver function. HBV-DNA and HBsAg were positive. All 32 patients received oral antiviral treatment (3 lamivudine, 21 entecavir, and 8 tenofovir) between 1 day and 4 months after diagnosis of acute hepatitis B. One patient died, 2 were transplanted, one died shortly after LTx the other patient survived after LTx. These 3 patients received treatment in a state of advanced liver failure, and 1 patient 4 months after initial diagnosis of hepatitis B. Twenty-nine patients survived without LTx. Five patients were discharged without further follow-up. All 24 remaining patients became HBV-DNA negative in median of 100 days. Twenty-two patients were followed further, and all patients lost their HBsAg in median of 108 days. Sixteen of the 22 patients experienced a seroconversion to anti-HBs in median of 137 days. Four patients who were followed for 1 more year after HBsAg did not develop anti-HBs. None of the patients developed chronic hepatitis B.

Conclusion: Immediate treatment of HBV-induced ALF with nucleos(t)id-analogues (NUCs) appears save and prevents LTx and death, and there is no indication for increased chronicity.

Zusammenfassung

Hintergrund: Akute Hepatitis-B-Virus (HBV) Infektion stellt immer noch eine bedeutende Ursache für das akute Leberversagen (ALV) dar und ist verbunden mit einer hohen Rate an High-Urgency Lebertransplantationen. Die akute Infektion führt über Virusreplikation und Zelltod schließlich zum ALV. Die Grundlage für die Behandlung der akuten fulminanten Hepatitis B ist daher durch Unterdrückung der Virusreplikation den Zelltod zu stoppen und die Regeneration der Leber zu unterstützen.

Studienziel: Ziel dieser retrospektiven Analyse war die Evaluation des optimalen Zeitpunktes, der Sicherheit und des Langzeit virologischen Ergebnisses dieser Therapie.

Methoden/Ergebnisse: In dieser Studie wurden 32 Patienten [16 Frauen und 16 Männer, medianes Alter 39,5 Jahre] mit ALV durch akute fulminante Hepatitis B retrospektiv untersucht, die in das Universitätsklinikum Essen zwischen Januar 2009 und Dezember 2013 stationär behandelt wurden. Vor Therapiebeginn waren die Transaminasen und Bilirubin stark erhöht; und ein erhöhter INR zeigte eine eingeschränkte Lebersyntheseleistung. HBV DNA und HBsAg waren positiv. Alle 32 Patienten erhielten orale antivirale Therapie (3 Lamivudin, 21 Entecavir und 8 Tenofovir) zwischen 1 Tag und 4 Monaten nach Diagnosestellung einer akuten Hepatitis B. Ein Patient starb, zwei erhielten eine Lebertransplantation von denen ein Patient kurz nach Transplantation starb. Bei diesen drei Patienten wurde die Therapie erst in einem Stadium fortgeschrittenen ALV begonnen, bei einem Patienten 4 Monate nach Diagnosestellung einer akuten Hepatitis B. 29 Überlebten ohne Transplantation. 5 Patienten wurden entlassen ohne weitere Kontrolluntersuchungen. Alle 24 übrigen Patienten wurden HBV-DNA negativ im median von 100 Tagen. 22 Patienten wurden weiter beobachtet und alle Patienten verloren das HBsAg im Median von 108 Tagen. 16 der 22 Patienten zeigten eine Serokonversion zu anti-HBs in einem Median von 137 Tagen. Vier Patienten, die für mehr als ein Jahr nach HBsAg-Verlust nachbeobachtet wurden entwickelten kein anti-HBs. Kein Patient entwickelte eine chronische Hepatitis B.

Zusammenfassung: Sofortige Therapie des ALV bei akuter fulminanter Hepatitis B mit Nucleos(t)id-Analogen erscheint sicher und kann Lebertransplantation und Tod verhindern und begünstigt nicht die Entwicklung einer chronischen Hepatitis B.

Schlüsselwörter

Hepatitis B - Akutes Leberversagen - Virushepatitis

Key words

Hepatitis B - acute liver failure - virus hepatitis
 

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