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Hepatitis D virus reinfection following liver transplantation

Anna SF Lok, MD
Section Editor
Robert S Brown, Jr, MD, MPH
Deputy Editor
Kristen M Robson, MD, MBA, FACG


Hepatitis D virus (HDV) infection is uncommon in the United States. Less than 3 percent of patients with acute hepatitis B virus (HBV) infection are coinfected with HDV. Based on studies conducted more than 20 years ago, it was estimated that approximately 70,000 Americans are chronic carriers of HDV and that as many as 1000 die of HDV-related liver disease each year [1]. These data have not been updated.

The clinical course of infection with HDV, which generally occurs only in patients coinfected with HBV, is highly variable [1,2]. As an example, although coinfection with HDV and HBV usually causes self-limited acute hepatitis, a high incidence of fulminant hepatic failure has been reported among intravenous drug users [2]. Similarly, superinfection of HDV in HBV carriers may be clinically inapparent or it may manifest as an exacerbation of preexisting chronic hepatitis with rapid progression to cirrhosis [3].

Since medical management of HDV-related liver disease has limited efficacy, some patients will require liver transplantation [4,5]. A 1995 annual report estimated that only a minority (10 to 20 percent) of the approximately 100 liver transplantations performed annually in the United States for HBV-related liver failure are in patients with concomitant HDV infection [6].

This topic will review hepatitis D virus reinfection following liver transplantation. The pathogenesis, clinical manifestations, prevention, and treatment of HDV infection are discussed separately (see "Pathogenesis, epidemiology, natural history, and clinical manifestations of hepatitis D virus infection" and "Treatment and prevention of hepatitis D virus infection").


Reinfection with hepatitis D virus (HDV) alone following liver transplantation is usually short-lived and not associated with recurrent liver disease unless hepatitis B virus (HBV) reinfection occurs subsequently. However, HDV reinfection can occur in the absence of markers of HBV reinfection, an observation that has provided important insights into the biology of HDV replication and the pathogenesis of HDV-related liver disease.

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Literature review current through: Nov 2017. | This topic last updated: Dec 15, 2016.
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  1. Alter MJ, Hadler SC. Delta hepatitis and infection in North America. Prog Clin Biol Res 1993; 382:243.
  2. Hoofnagle JH. Type D (delta) hepatitis. JAMA 1989; 261:1321.
  3. Rizzetto M, Durazzo M. Hepatitis delta virus (HDV) infections. Epidemiological and clinical heterogeneity. J Hepatol 1991; 13 Suppl 4:S116.
  4. Farci P, Mandas A, Coiana A, et al. Treatment of chronic hepatitis D with interferon alfa-2a. N Engl J Med 1994; 330:88.
  5. Rosina F, Pintus C, Meschievitz C, Rizzetto M. A randomized controlled trial of a 12-month course of recombinant human interferon-alpha in chronic delta (type D) hepatitis: a multicenter Italian study. Hepatology 1991; 13:1052.
  6. Annual Report of the US Scientific Registry of Transplant Recipients and the Organ Procurement and Transplantation Network. US Department of Health and Human Services, 1995.
  7. Modahl LE, Lai MM. Hepatitis delta virus: the molecular basis of laboratory diagnosis. Crit Rev Clin Lab Sci 2000; 37:45.
  8. Mason WS, Taylor JM. Experimental systems for the study of hepadnavirus and hepatitis delta virus infections. Hepatology 1989; 9:635.
  9. Mason WS, Taylor JM. Liver transplantation: a model for the transmission of hepatitis delta virus. Gastroenterology 1991; 101:1741.
  10. Glenn JS, Taylor JM, White JM. In vitro-synthesized hepatitis delta virus RNA initiates genome replication in cultured cells. J Virol 1990; 64:3104.
  11. Netter HJ, Gerin JL, Tennant BC, Taylor JM. Apparent helper-independent infection of woodchucks by hepatitis delta virus and subsequent rescue with woodchuck hepatitis virus. J Virol 1994; 68:5344.
  12. Smedile A, Casey JL, Cote PJ, et al. Hepatitis D viremia following orthotopic liver transplantation involves a typical HDV virion with a hepatitis B surface antigen envelope. Hepatology 1998; 27:1723.
  13. Samuel D, Zignego AL, Reynes M, et al. Long-term clinical and virological outcome after liver transplantation for cirrhosis caused by chronic delta hepatitis. Hepatology 1995; 21:333.
  14. Mederacke I, Filmann N, Yurdaydin C, et al. Rapid early HDV RNA decline in the peripheral blood but prolonged intrahepatic hepatitis delta antigen persistence after liver transplantation. J Hepatol 2012; 56:115.
  15. Ottobrelli A, Marzano A, Smedile A, et al. Patterns of hepatitis delta virus reinfection and disease in liver transplantation. Gastroenterology 1991; 101:1649.
  16. Zignego AL, Dubois F, Samuel D, et al. Serum hepatitis delta virus RNA in patients with delta hepatitis and in liver graft recipients. J Hepatol 1990; 11:102.
  17. Demetris AJ, Todo S, Van Thiel DH, et al. Evolution of hepatitis B virus liver disease after hepatic replacement. Practical and theoretical considerations. Am J Pathol 1990; 137:667.
  18. David E, Rahier J, Pucci A, et al. Recurrence of hepatitis D (delta) in liver transplants: histopathological aspects. Gastroenterology 1993; 104:1122.
  19. Davies SE, Lau JY, O'Grady JG, et al. Evidence that hepatitis D virus needs hepatitis B virus to cause hepatocellular damage. Am J Clin Pathol 1992; 98:554.
  20. Lau JY, Portmann BC, Alexander GJ, Williams R. Differential effect of chronic hepatitis D virus infection on intrahepatic expression of hepatitis B viral antigen. J Clin Pathol 1992; 45:314.
  21. Samuel D, Muller R, Alexander G, et al. Liver transplantation in European patients with the hepatitis B surface antigen. N Engl J Med 1993; 329:1842.
  22. Lerut JP, Donataccio M, Ciccarelli O, et al. Liver transplantation and HBsAg-positive postnecrotic cirrhosis: adequate immunoprophylaxis and delta virus co-infection as the significant determinants of long-term prognosis. J Hepatol 1999; 30:706.
  23. Rifai K, Wedemeyer H, Rosenau J, et al. Longer survival of liver transplant recipients with hepatitis virus coinfections. Clin Transplant 2007; 21:258.
  24. Krogsgaard K, Kryger P, Aldershvile J, et al. Delta-infection and suppression of hepatitis B virus replication in chronic HBsAg carriers. Hepatology 1987; 7:42.
  25. Genesca J, Jardi R, Buti M, et al. Hepatitis B virus replication in acute hepatitis B, acute hepatitis B virus-hepatitis delta virus coinfection and acute hepatitis delta superinfection. Hepatology 1987; 7:569.
  26. Taniguchi M, Shakil AO, Vargas HE, et al. Clinical and virologic outcomes of hepatitis B and C viral coinfection after liver transplantation: effect of viral hepatitis D. Liver Transpl 2000; 6:92.
  27. Saigal S, Smith HM, Heaton ND, et al. Suppression of hepatitis B and hepatitis C viremia by concurrent delta virus infection: Its beneficial effect on the outcome of orthotopic liver transplantation (abstract). Hepatology 1999; 30:302A.
  28. Pontisso P, Ruvoletto MG, Fattovich G, et al. Clinical and virological profiles in patients with multiple hepatitis virus infections. Gastroenterology 1993; 105:1529.
  29. Roche B, Samuel D. Liver transplantation in delta virus infection. Semin Liver Dis 2012; 32:245.
  30. Lake JR, Wright TL. Liver transplantation for patients with hepatitis B: what have we learned from our results? Hepatology 1991; 13:796.
  31. Gish RG, Keeffe EB, Lim J, et al. Survival after liver transplantation for chronic hepatitis B using reduced immunosuppression. J Hepatol 1995; 22:257.
  32. Wright HI, Gavaler JS, Van Theil DH. Preliminary experience with alpha-2b-interferon therapy of viral hepatitis in liver allograft recipients. Transplantation 1992; 53:121.
  33. Rasshofer R, Choi SS, Wolf P, et al. of HDV RNA replication in vitro by ribavirin and suramin. In: Viral Hepatitis and liver Disease, Hollinger FB, Lemon SM, Margolis HS (Eds), Williams and Wilkins, Baltimore 1991. p.659.