eMedicine Specialties > Gastroenterology > Liver

Hepatitis D

Author: Sean R Lacey, MD, Associate Professor of Gastroenterology, Penn State College of Medicine
Contributor Information and Disclosures

Updated: Jan 3, 2010

Introduction

Background

Hepatitis D virus (HDV) is an RNA virus that is structurally unrelated to hepatitis A, B, or C virus. It was discovered in 1977. HDV causes a unique infection that requires the assistance of viral particles from hepatitis B virus (HBV) to replicate and infect other hepatocytes.1,2,3 Its clinical course is varied and ranges from acute self-limited infection to acute fulminant liver failure. Chronic liver infection can lead to end-stage liver disease and associated complications.4,5,6

Pathophysiology

HDV infection is an acute and chronic inflammatory process involving the liver. Three known genotypes are described. Genotype I has a worldwide distribution. Genotype 2 has been discovered in Taiwan, Japan, and northern Asia. Genotype 3 is found in South America. HDV can replicate independently within the hepatocyte, but it requires hepatitis B surface antigen (HBsAg) for propagation. Hepatic cell death may occur due to the direct cytotoxic effect of HDV or via a host-mediated immune response.

Frequency

United States

HDV infection occurs more commonly among adults than children. It is observed more commonly among patients with a history of intravenous drug use and in persons from the Mediterranean basin.

International

Approximately 15 million people are infected worldwide. Areas with the highest prevalence include southern Italy; North Africa; the Middle East; the Amazon Basin; and the American South Pacific islands of Samoa, Hauru, and Hiue. China, Japan, Taiwan, and Myanmar (formerly Burma) have a high prevalence of HBV infection but a low rate of HDV infection.

Mortality/Morbidity

  • Simultaneous infection with HBV and HDV is known as coinfection and results in fulminant liver failure in 1% of patients. Complete clinical recovery and clearance of HBV and HDV coinfection is the most common outcome. Chronic infection with HBV and HDV occurs in less than 5% of patients.
  • Infection with HDV in a patient already HBsAg-positive is known as superinfection and results in fulminant liver failure in 5% of patients. Approximately 80-90% develop chronic HDV infection. These patients progress more rapidly to develop cirrhosis and may develop hepatocellular carcinoma.
  • A study from The Netherlands suggested HDV may hinder the control of HBV. Xiridou et al used a mathematical model for the transmission of both viruses and calculated the reproduction numbers of single HBV infections and dual HBV/HDV infections.3 The investigators looked at the endemic prevalences of both viruses and found HDV modulates HBV epidemic severity as well as has a hampering impact on HBV interventions. Xiridou et al concluded that in endemic populations with HDV, control programs that ignore HDV presence may lead to underestimation of the HBV epidemic and overestimation of positive results, as control of HBV is dependent on the reproduction numbers of dual HBV/HDV infections.3

Sex

  • HDV infection is not associated with a sex predilection.

Age

  • HDV infection is more common among adults than children. However, children from underdeveloped, HDV-endemic countries are more likely to contract HDV infection through breaks in the skin due to the presence of skin lesions.

Clinical

History

  • HDV infection is clinically indistinguishable from other forms of viral hepatitis.
  • As many as 90% of patients are asymptomatic.
  • The incubation period is 21-45 days but may be shorter in cases of superinfection.
  • Symptoms include the following:
    • Jaundice
    • Dark urine
    • Abdominal pain
    • Nausea with vomiting
    • Confusion, bruising, and bleeding (rare)
    • Pruritus

Physical

  • Symptoms upon presentation include the following:
    • Scleral icterus
    • Fever
    • Abdominal pain, usually right upper quadrant
    • Tea-colored urine
    • Encephalopathy (rare)
    • Petechia with bruising (rare)

Causes

  • HDV is transmitted parenterally.
  • Risk factors include intravenous drug use and multiple blood transfusions.
  • Sexual transmission is less efficient than with HBV.
  • Perinatal transmission is rare; no such cases have been reported in the United States.

More on Hepatitis D

Overview: Hepatitis D
Differential Diagnoses & Workup: Hepatitis D
Treatment & Medication: Hepatitis D
Follow-up: Hepatitis D
References
Further Reading
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References

  1. Rizzetto M, Verme G, et al. Delta hepatitis--present status. J Hepatol. 1985;1(2):187-93. [Medline].

  2. Bean P. Latest discoveries on the infection and coinfection with hepatitis D virus. Am Clin Lab. Jun 2002;21(5):25-7. [Medline].

  3. Xiridou M, Borkent-Raven B, Hulshof J, Wallinga J. How hepatitis D virus can hinder the control of hepatitis B virus. PLoS One. 2009;4(4):e5247. [Medline].

  4. 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. Jun 1998;27(6):1723-9. [Medline].

  5. 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. Feb 1995;21(2):333-9. [Medline].

  6. 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. May 2009;136(5):1629-38. [Medline].

  7. Manesis EK, Schina M, Le Gal F, et al. Quantitative analysis of hepatitis D virus RNA and hepatitis B surface antigen serum levels in chronic delta hepatitis improves treatment monitoring. Antivir Ther. 2007;12(3):381-8. [Medline].

  8. Alter MJ, Mast EE. The epidemiology of viral hepatitis in the United States. Gastroenterol Clin North Am. Sep 1994;23(3):437-55. [Medline].

  9. Borresen ML, Olsen OR, Ladefoged K, et al. Hepatitis D outbreak among children in a hepatitis B hyper-endemic settlement in Greenland. J Viral Hepat. Sep 25 2009;epub ahead of print. [Medline].

  10. Bozdayi AM, Aslan N, Bozdayi G, et al. Molecular epidemiology of hepatitis B, C and D viruses in Turkish patients. Arch Virol. Jul 15 2004.

  11. Caredda F, Rossi E, d'Arminio Monforte A, et al. Hepatitis B virus-associated coinfection and superinfection with delta agent: indistinguishable disease with different outcome. J Infect Dis. May 1985;151(5):925-8. [Medline].

  12. Dimitrakakis M, Crowe S, Gust I. Prevalence of delta infection in the western Pacific region. J Med Virol. Apr 1986;18(4):335-9. [Medline].

  13. Farci P. Delta hepatitis: an update. J Hepatol. 2003;39 Suppl 1:S212-9. [Medline].

  14. Farci P, Mandas A, Coiana A, et al. Treatment of chronic hepatitis D with interferon alfa-2a. N Engl J Med. Jan 13 1994;330(2):88-94. [Medline].

  15. Heidrich B, Deterding K, Tillmann HL, et al. Virological and clinical characteristics of delta hepatitis in Central Europe. J Viral Hepat. Dec 2009;16(12):883-94. [Medline].

  16. Hoofnagle JH, di Bisceglie AM. The treatment of chronic viral hepatitis. N Engl J Med. Jan 30 1997;336(5):347-56. [Medline].

  17. Lau DT, Doo E, Park Y, et al. Lamivudine for chronic delta hepatitis. Hepatology. Aug 1999;30(2):546-9. [Medline].

  18. Makuwa M, Mintsa-Ndong A, Souquiere S, et al. Prevalence and molecular diversity of hepatitis B virus and hepatitis delta virus in urban and rural populations in northern Gabon in central Africa. J Clin Microbiol. Jul 2009;47(7):2265-8. [Medline].

  19. Ponzetta A, Forzani E, Shafi MS. Delta agent infection in Saudi Arabia: a general population study. In: Vyas GN, Dienstag JL, Hoofnagle JH, eds. Viral Hepatitis. New York, NY: Grune and Stratton; 1984:634.

  20. Rizzetto M. Hepatitis D: thirty years after. J Hepatol. May 2009;50(5):1043-50. [Medline].

  21. Rizzetto M, Canese MG, Arico S. Immunofluorescence detection of new antigen-antibody system (delta/anti- delta) associated to hepatitis B virus in liver and in serum of HBsAg carriers. Gut. Dec 1977;18(12):997-1003. [Medline].

  22. Rosina F, Conoscitore P, Cuppone R, et al. Changing pattern of chronic hepatitis D in Southern Europe. Gastroenterology. Jul 1999;117(1):161-6. [Medline].

  23. Rosina F, Cozzolongo R. Interferon in HDV infection. Antiviral Res. Jul 1994;24(2-3):165-74. [Medline].

  24. Smedile A, Dentico P, Zanetti A, et al. Infection with the delta agent in chronic HBsAg carriers. Gastroenterology. Dec 1981;81(6):992-7. [Medline].

  25. Taylor JM. Therapy for HDV!. Hepatology. Dec 2003;38(6):1581-2. [Medline].

  26. Verme G, Brunetto MR, Oliveri F, et al. Role of hepatitis delta virus infection in hepatocellular carcinoma. Dig Dis Sci. Aug 1991;36(8):1134-6. [Medline].

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Further Reading

Related eMedicine Topics

Clinical Trials
 Clinical Guidelines

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Keywords

hepatitis D, HDV, HDV infection, viral hepatitis, delta hepatitis, delta virus, hepatitis delta, hepatitis B virus, HBV, hepatitis B surface antigen, HBsAg, liver failure, liver infection, acute fulminant liver failure, chronic liver infection, end-stage liver disease, end-stage liver disease, ESLD, cirrhosis, hepatocellular carcinoma, HCC, liver transplantation, hepatic transplantation

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Contributor Information and Disclosures

Author

Sean R Lacey, MD, Associate Professor of Gastroenterology, Penn State College of Medicine
Sean R Lacey, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, and American Gastroenterological Association
Disclosure: astra zenaca Honoraria Speaking and teaching

Medical Editor

David Eric Bernstein, MD, Chief, Section of Hepatology, North Shore University Hospital, Director, Associate Professor, Department of Internal Medicine, Division of Hepatology, New York University School of Medicine
David Eric Bernstein, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Oscar S Brann, MD, FACP, Associate Clinical Professor, Department of Medicine, University of California at San Diego; Consulting Staff, Mecklenburg Medical Group
Oscar S Brann, MD, FACP is a member of the following medical societies: American Gastroenterological Association
Disclosure: Nothing to disclose.

CME Editor

Alex J Mechaber, MD, FACP, Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine
Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD, Clinical Professor of Medicine, Drexel University College of Medicine; Consulting Staff, Department of Medicine, Section of Gastroenterology and Hepatology, Hospital of the Medical College of Pennsylvania
Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law Medicine and Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

 
 
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