Background
Hepatitis D virus (HDV) is an RNA virus that was discovered in 1977 and is structurally unrelated to the hepatitis A (HAV), hepatitis B (HBV), and hepatitis C (HCV) viruses. HDV causes a unique infection that requires the assistance of HBV viral particles to replicate and infect hepatocytes. [1, 2, 3, 4] 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 (including accelerated fibrosis, liver decompensation, and hepatocellular carcinoma). [5, 6, 7, 8, 9, 10]
There are three known genotypes of HDV. Genotype 1 has a worldwide distribution; genotype 2 exists in Taiwan, Japan, and northern Asia; and genotype 3 is found in South America.
Simultaneous coinfection with HBV and HDV occurs in 5-15% of those with HBV [8, 11] and results in fulminant liver failure in 1% of patients. HBV-HDV coinfection is the most aggressive form of viral hepatitis. [8, 12, 13] Complete clinical recovery and clearance of HBV and HDV coinfection is the most common outcome. (See Prognosis and Workup.)
Infection with HDV in a patient who is already positive for the hepatitis B surface antigen (HBsAg) 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. (See Workup.)
A study from The Netherlands suggested that 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 prevalence of both viruses and found that HDV modulates HBV epidemic severity and also hampers the impact on HBV interventions. Xiridou et al concluded that in endemic populations with HDV, control programs that ignore HDV presence may lead to an underestimation of the HBV epidemic and an overestimation of positive results, as control of HBV is dependent on the reproduction numbers of dual HBV/HDV infections. [3] (See Epidemiology.)
See the following Medscape Drugs & Diseases topics for more information:
Etiology
Hepatitis D virus (HDV) infection is an acute and chronic inflammatory process involving the liver. HDV is transmitted parenterally; it 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.
Risk factors include intravenous drug use (IVDU) and multiple blood transfusions. A study of 652 North American patients infected with hepatitis B virus (HBV) found 91 with concurrent HDV infection; independent risk factors for HDV included the following [14] :
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IVDU
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HBV-DNA measured below 2000 IU/mL
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Alanine aminotransferase (ALT) level above 40 U/L
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HDV endemicity at the country of origin
Sexual transmission is less efficient than with HBV.
Perinatal transmission is rare; no such cases have been reported in the United States.
Epidemiology
Widespread vaccination against hepatitis B in developed nations has helped to reduce the incidence of HDV infection. [10] In the United States, hepatitis D virus (HDV) infection is observed more commonly among patients with a history of intravenous drug use and in persons from the Mediterranean basin.
Initial studies estimated approximately 15-20 million people are coinfected with HDV and HBV worldwide. [11, 15] More recent studies suggest that the global prevalence of HDV is probably two to three times higher than previously estimated. [11] Areas with the highest HDV prevalence include regions with high migration of populations from HDV endemic countries and less wealthy nations, [10] as well as southern Italy; North Africa; the Middle East; the Amazon Basin [16] ; and the American South Pacific islands of Samoa, Hauru, and Hiue. Although China, Japan, Taiwan, and Myanmar (formerly Burma) have a high prevalence of HBV infection, they have a low rate of HDV infection. [17, 18]
A 2017 case-control study from Northern Spain (1983-2012) that evaluated the prevalence and epidemiology of HDV infection among those infected with HBV found an 8.2% prevalence of anti-HDV. [19] In the analysis of patients grouped into years 1983-1997 (group A) and 1998-2012 (group B), the investigators noted that the prevalence of anti-HDV fell from 9.4% in the first group to 6.1% in the second group. Moreover, independent risk factors related to the presence of anti-HDV differed between the two groups, with intravenous drug use (IVDA), blood transfusion, and high alanine aminotransferase (ALT) levels affecting the earlier group, whereas immigration, IVDA, promiscuous sexual activity, and elevated ALT levels predominantly affected the latter group. [19]
HDV infection is more common in adults than in 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.
Prognosis
The prognosis is excellent for patients with coinfection in whom treatment eradicates both viruses.
The prognosis is variable for patients who are superinfected. It depends on the duration and severity of hepatitis B virus (HBV) infection, alcohol consumption, comorbid illnesses, and age.
In patients who undergo liver transplantation for chronic liver disease secondary to HBV and hepatitis D virus (HDV) infections, HDV seems to suppress the replication of HBV in the transplanted liver and may help to prolong graft survival. However, fulminant hepatitis from recurrent HBV and HDV infections in the transplanted liver has resulted in patient death or the need to retransplant.
HBV-HDV superinfection significantly increases adult morbidity and mortality. [20] In a 2017 nationwide study that evaluated risk factors associated with chronic HBV infection in France (2008-2013), investigators noted that coinfection with HDV or HCV, alcohol use disorders, diabetes mellitus, and other rare causes of chronic liver disease all increased the risk of all-cause mortality, particularly following progression of liver disease. [12]
Complications
Complications of HDV infection may include the following:
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Liver failure
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Hepatocellular carcinoma
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Autoimmune manifestations, often including antinuclear antibodies and smooth muscle antibodies
Patient Education
Educate patients regarding modification of high-risk behaviors, including intravenous drug use and unsafe sexual practices.
Promote the use of universal precautions for health care workers.
Discuss with patients with chronic hepatitis D virus (HDV) and hepatitis B virus (HBV) infections that they should not donate blood, share toothbrushes or razors, or consume alcohol. Precautions should be observed regarding blood and body fluids.
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Algorithm for the evaluation of chronic hepatitis D. Courtesy of Gastroenterology Report (Shah PA, Choudhry S, Reyes KJC, Lau DTY. An update on the management of chronic hepatitis D. Gastroenterol Rep (Oxf). 2019 Oct 19;7(6):396-402. PMID: 32494363; PMCID: PMC7249531).
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Algorithm for the treatment of chronic hepatitis D. Courtesy of Gastroenterology Report (Shah PA, Choudhry S, Reyes KJC, Lau DTY. An update on the management of chronic hepatitis D. Gastroenterol Rep (Oxf). 2019 Oct 19;7(6):396-402. PMID: 32494363; PMCID: PMC7249531).
