Published May 29, 2002Talal Adhami, MD |
Viral liver disease, particularly with the current hepatitis C epidemic, presents a challenging and frequently encountered problem for practicing physicians. The literature on this subject is vast and rapidly increasing and new and promising therapies are being offered to patients. Five viruses designated hepatitis A, B, C, D and E infect the liver and produce hepatitis as their primary clinical manifestation. Hepatitis G virus has been identified more recently, but its role in causing liver disease is not clearly defined. Other viruses, such as Epstein-Barr (EBV) and cytomegalovirus (CMV), may cause hepatitis as part of their clinical presentation but the liver is usually not the primary target organ. This chapter section covers hepatitis D. The other hepatitis viruses are discussed in separate sections and can be viewed by clicking on the hyperlinks on the right-hand side of this page. |
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DefinitionPrevalencePathophysiology/
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Hepatitis D or delta virus (HDV) is a defective, single-stranded RNA virus requiring the presence of hepatitis B virus (HBV) for its expression and replication. HDV is a 35-37 nm spherical particle enveloped by HBV lipoprotein coat. HDV-RNA consists of 1680 nucleotides and replication is limited to hepatocytes. It is considered to be the smallest RNA genome amongst the animal viruses.
Patients may be infected with HDV at the same time they acquire the hepatitis B virus (co-infection) or acquire the virus after infection with hepatitis B (superinfection). It is still not clear whether the virus is directly cytotoxic or an immune-mediated response is responsible for the pathology. An immune response may be the predominant mediator in chronic disease, whereas direct viral cytotoxicity may predominate in acute infection. Necroinflammatory activity is severe, but histological features are nonspecific for chronic HDV infection.1
Symptoms of HDV infection are nonspecific and most patients have subclinical illness. The majority of patients who acquire HDV and HBV simultaneously clear the delta virus, whereas 70% to 90% of those superinfected will develop chronic delta infection. Superinfection produces more severe acute illness than HBV alone and carries a higher risk for fulminant hepatic failure, which occurs in 5% to 20% of cases.2
Measuring antibodies to delta antigen using enzyme-linked immunosorbent assay (ELISA) can make the diagnosis. Immunoglobulin M (IgM) antibodies are increased when there is liver damage and not just in the acute illness and appear to disappear when there is resolution of the hepatitis. HDV-Ag is detectable in the nuclei and to a lesser extent in the cytoplasm of infected cells and serum, as is HDV-RNA, detected by molecular hybridization. The current and preferred diagnostic test of choice is the detection of viral RNA in the serum using a reverse transcriptase polymerase chain reaction (PCR). This test is very sensitive in detecting infection and its absence almost certainly reflects absence of the virus.
Delta hepatitis can be prevented by vaccination against hepatitis B. At this time there is no effective vaccine to prevent delta hepatitis in chronic hepatitis B carriers. Delta hepatitis can be treated with high-dose interferon as high as 9 million units 3 times per week for 1 year. Although as many as 70% may clear the virus and normalize liver enzymes, almost all relapse at some point after therapy. Orthotopic liver transplantation is considered in decompensated patients. Interestingly, patients with HDV who are transplanted have a higher chance of graft survival than those who are transplanted for hepatitis B alone. This phenomenon may be due to the inhibitory effect of HDV on HBV replication. Hepatitis B immunoglobulin is administered to these patients.
Co-infection with HDV and HBV may result in a severe, fulminant hepatitis and liver failure or persist as a chronic infection resulting in cirrhosis or hepatocellular carcinoma. Chronic infection may persist in an inactive phase and some patients may go into complete remission. The chance of progression to cirrhosis is higher in patients with delta hepatitis than in patients solely with hepatitis B as is the risk for hepatocellular carcinoma. Patients co-infected with HIV or hepatitis C have a worse outcome.3,4