Rapid early HDV RNA decline in the peripheral blood but prolonged intrahepatic hepatitis delta antigen persistence after liver transplantation

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• 作者：Ingmar Mederacke¹ ;   ; ⁸ ; Natalie Filmann² ; Cihan Yurdaydin³ ; Birgit Bremer¹ ; Florian Puls⁴ ; Behrend Johann Zacher¹ ; Benjamin Heidrich¹ ;   ; ⁸ ; Hans Ludger Tillmann⁵ ; Jens Rosenau¹ ; C.-Thomas Bock⁶ ; Berna Savas³ ; Fabian Helfritz⁷ ; Frank Lehner⁷ ;   ; ⁸ ; Christian P. Strassburg¹ ;   ; ⁸ ; Juergen Klempnauer⁷ ;   ; ⁸ ; Karsten Wursthorn¹ ; Ulrich Lehmann⁴ ;   ; ⁸ ; Michael P. Manns¹ ;   ; ⁸ ; Eva Herrmann² ; Heiner Wedemeyer¹ ;   ; ⁸ ;   ; ^{wedemeyer.heiner@mh-hannover.de}
• 关键词：Hepatitis delta ; HDAg staining ; Liver transplantation ; Prophylaxis of reinfection ; Hepatitis B immunoglobulin (HBIG) ; Mathematical modeling
• 刊名：Journal of Hepatology
• 出版年：2012
• 出版时间：January 2012
• 年：2012
• 卷：56
• 期：1
• 页码：115-122
• 全文大小：1107 K

文摘

Background & Aims

Chronic HDV infection is an inflammatory liver disease and liver transplantation (LTX) remains the only curative treatment option for most patients. The hepatitis D virus (HDV) uses HBsAg as its surface protein, however, it is controversial to what extend HDV may be detected independently of HBsAg in blood and liver after LTX. The aims of this study were to investigate kinetics of HDV RNA and HBsAg early after LTX, to apply the data to a mathematical model and to study long-term persistence of HDV after LTX.

Methods

We retrospectively analyzed 26 patients with chronic hepatitis delta who underwent LTX between 1994 and 2009. Blood samples were obtained every 1? days during the first 14 days after LTX. Data were applied to a mathematical model to study viral kinetics. Available liver biopsy samples were stained for HBV and HDV viral antigens and tested for HBV DNA/cccDNA.

Results

HBsAg and HDV RNA became negative after a median of 5 days (range 1?3) and 4 days (range 1?0), respectively. Early HDV RNA and HBsAg decline paralleled almost exactly in all patients; however the mathematical model showed a high variability of virion death. HDAg stained positive in transplanted livers in six patients in the absence of liver HBV DNA/cccDNA, serum-HBsAg, and HDV RNA for up to 19 months after LTX.

Conclusions

HDV RNA and HBsAg decline follow almost identical kinetic patterns within the first days after LTX. Nevertheless, intrahepatic latency of HDAg has to be considered when exploring novel concepts to withdraw HBIG.