| disease | Hepatitis D |
| alias | Viral Hepatitis D, Hepatitis D, HD |
Viral hepatitis D is a pestilence caused by the hepatitis D virus in conjunction with hepatitis B virus and other hepatotropic DNA viruses. It is primarily transmitted through blood transfusions and blood products, similar to the transmission routes of hepatitis B. Coinfection with HDV and HBV can exacerbate liver damage and is prone to progress into chronic active hepatitis, liver cirrhosis, and severe hepatitis.
bubble_chart Epidemiology
This disease has a worldwide distribution, with particularly high endemicity in southern Italy. Developing countries exhibit a higher HBsAg carrier rate, providing a basis for HDV infection. Reports from China indicate localized endemic outbreaks, with HDV infection rates among HBsAg-positive individuals ranging from 0% to 32%. Overall, the rates are lower in the north and higher in the south. The HDV infection rate is significantly higher in patients with severe hepatitis and chronic liver disease compared to asymptomatic HBsAg carriers.
Since Rizzetto et al. from Italy reported the
δ antigen-antibody system in 1977, in-depth research on the δ antigen and related hepatitis has led to a comprehensive understanding of the δ factor. In 1984, Rizzetto et al. proposed naming it the hepatitis D virus (HDV), hepatitis D antigen (HDAg), and hepatitis D (HD), which has been widely accepted by scholars worldwide. Studies have shown that HDV is a defective single-stranded negative-sense RNA virus that relies on HBV or other hepatotropic DNA viruses to provide its outer coat for replication. HDV is found in the nuclei of liver cells and the serum of HBsAg-positive HDV-infected individuals, primarily replicating within liver cells. HDV is prone to mutation. Human infection with HDV significantly inhibits HBV-DNA synthesis. Serological tests indicate that the appearance of HDAg coincides with a reduction in HBV-DNA in the serum. As HDAg turns negative and anti-HD appears, HBV-
DNA levels return to their original state. The disease has a global distribution, with particularly high endemicity in southern Italy. Developing countries have higher HBsAg carrier rates, creating a foundation for HDV infection. Reports from China suggest localized outbreaks, with HDV infection rates among HBsAg-positive individuals ranging from 0% to 32%. Overall, rates are lower in the north and higher in the south. The HDV infection rate is significantly higher in patients with severe hepatitis and chronic liver disease compared to asymptomatic HBsAg carriers. Transmission primarily occurs through blood transfusions and blood products, similar to hepatitis B. HDV infection is mostly seen in HBV-infected individuals, though sporadic HDV infections also occur. Coinfection with HDV and HBV can exacerbate liver damage and increase the risk of progressing to chronic active hepatitis, cirrhosis, and severe hepatitis. Strict screening of blood donors is an effective way to reduce post-transfusion hepatitis D, while widespread vaccination against hepatitis B is a powerful measure to ultimately eliminate the HBsAg carrier state and a practical approach to controlling HDV infection.The pathogenesis of this disease has not been fully elucidated. Currently, it is believed that HDV has a direct damaging effect on hepatocytes, and host immune responses also play a mediating role.
bubble_chart Pathological Changes
Can HDV cause characteristic hepatocellular changes in sexually transmitted diseases? Reports from various scholars are inconsistent. Most believe that the pathological features of hepatitis D include hepatocellular eosinophilic degeneration and microvesicular fatty degeneration, accompanied by inflammatory cell infiltration and portal inflammatory reactions. In chronic HBV carriers, co-infection with HDV can exacerbate liver tissue damage. However, recent reports indicate that in chronic HBsAg carriers with chronic HDV infection, liver tissue shows no significant changes. In patients with chronic active hepatitis or chronic persistent hepatitis, the clinical outcomes after HDV co-infection appear to be similar to those with HBV infection alone. Compared to HDAg-negative liver tissue, HDAg-positive liver tissue shows no significant difference in the severity of pathological changes.
After a person is infected with HDV, the clinical manifestations depend on the pre-existing HBV infection status. The incubation period ranges from 4 to 20 weeks. There are two types as follows:
1. Coinfection of HDV and HBV
This occurs in individuals with no prior HDV infection who are simultaneously infected with HDV and HBV, presenting as acute hepatitis D. The clinical symptoms are similar to those of acute hepatitis B, with two peaks of bilirubin and ALT elevation observed during the course of the disease. HBsAg appears first in the serum, followed by the presence of HDAg in the liver. In acute cases, HDAg in the serum remains positive for only a few days before turning negative, after which anti-HD IgM becomes positive, lasting for a short duration and at a low titer. Anti-HD IgG remains negative.
2. Superinfection of HDV on HBV
The clinical manifestations vary and may resemble acute hepatitis, chronic hepatitis, or severe hepatitis.
This is more common in chronic HBV carriers, and the symptoms primarily depend on whether the individual was a chronic HBsAg carrier or had chronic HBV-related liver disease prior to HDV infection. If the individual was an HBsAg carrier, HDV infection may present as acute HBsAg-positive hepatitis, but anti-
HBV IgM is negative, and the condition is more severe than HBV infection alone. If the individual had chronic HBV-related liver disease, due to persistent HBV infection and continuous HDV replication, the existing liver tissue damage worsens, which may manifest as an acute hepatitis flare-up or accelerate progression to chronic active hepatitis and cirrhosis. Therefore, in cases of chronic hepatitis B where the condition was previously stable but suddenly deteriorates, even leading to liver failure resembling severe hepatitis, the possibility of HDV superinfection should be considered.
In recent years, the specific diagnostic methods for hepatitis D have included detecting HDAg or HDV-RNA in the liver and serum, or detecting anti-HD and anti-HD IgM in serum, all of which serve as diagnostic criteria.
1. HDAg
HDAg in serum can be detected using enzyme immunoassay or radioimmunoassay. A positive result aids in early diagnosis. In chronic HDV infection, due to the high titer of anti-HD in serum, HDAg often exists in the form of immune complexes. Western Blot is required to separate HDAg, making the method more complex. HDAg in the liver can be detected using immunofluorescence or immunohistochemical techniques, revealing its presence in the nucleus or cytoplasm of hepatocytes, which is beneficial for diagnosis.
2. Anti-HD and Anti-HD IgM
Serum anti-HD can be detected using enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay, which are common methods for diagnosing hepatitis D. During the acute phase of HDV infection (3–8 weeks), anti-HD can be detected in the vast majority of cases and may persist into the convalescent stage. Since the timing and levels of anti-HD appearance vary among individuals, multiple tests are necessary during the acute phase. Anti-HD IgM appears earlier, typically lasting 2–20 weeks, and is used for early diagnosis. A high titer of anti-HD IgM is a marker for acute hepatitis D. In chronic HDV infection or HDV superinfection, anti-HD and anti-HD IgG are primary markers for identifying chronic hepatitis D. Currently, the detected anti-HD is predominantly of the IgG type.
3. HDV-RNA
HDV-RNA can be detected using cDNA probe dot blot hybridization. In liver tissue, HDV-RNA is detected via in situ hybridization or blot hybridization. A positive HDV-RNA result is direct evidence of HDV replication and infection. Serum HDV-RNA can be detected using reverse transcription-polymerase chain reaction (RT-PCR).
In summary, serological testing can identify some patients with HDV infection, but a significant proportion of cases can only be confirmed by detecting HDAg in liver tissue.
The diagnosis of acute hepatitis D relies on specific serological tests. Clinically, when a chronic HBsAg carrier suddenly presents with symptoms resembling acute hepatitis, or exhibits a biphasic pattern of bilirubin and ALT elevation during the course of illness; or when a patient with chronic hepatitis B experiences sudden worsening of symptoms or rapid progression to chronic active hepatitis or severe hepatitis, HDV superinfection should be considered. Prompt specific serological testing should be conducted to aid in diagnosis.
bubble_chart Treatment Measures
There is currently no effective treatment for HDV infection, with prevention being the key focus. Clinical management primarily involves liver protection and symptomatic treatment. Antiviral drugs such as interferon mainly interfere with HBV-DNA synthesis and do not inhibit HDV-RNA synthesis. If HBV replication is reduced, it may lead to an increase in HDV-RNA synthesis. The use of immunomodulators has also shown no improvement.
1. Strict screening of blood donors to ensure the quality of blood and blood products is an effective method to reduce the incidence of post-transfusion hepatitis D.
2. Widespread vaccination of HBV-susceptible individuals with the hepatitis B vaccine is a powerful measure to ultimately eliminate the HBsAg carrier state and a practical method to control HDV infection.
3. Strictly implement disinfection and isolation protocols, aseptic techniques, and the use of disposable medical supplies or single-use disinfection for needles and injections to prevent iatrogenic transmission.
