Virus structure and pathogenesis of the lesion
Hepatitis D virus (HDV) is a small, defective, spherical virus with a diameter of 35–37 nm. Since its genome does not encode envelope proteins, it borrows the surface antigen (HBsAg) from the hepatitis B virus (HBV) to create a complete virion. In Russia, the HDV-1 genotype is most commonly found.
The replication process occurs in the hepatocyte nucleus without the direct participation of HBV. The genome doubles via a rolling-circle mechanism, making HDV similar to plant viroids. The synthesized delta antigen (HDAg) concentrates in the nucleus and does not reach the cell membrane. Because of this, it does not become a target for cell-mediated immunity, and the antibodies produced do not carry protective functions. Liver destruction occurs due to the direct cytotoxic action of the virus. At the same time, active HDV replication eventually suppresses the activity of the helper virus (HBV).
Coinfection: simultaneous HBV and HDV infection
Develops when both viruses enter the body simultaneously. To start delta-agent replication, the accumulation of a sufficient amount of HBsAg is necessary, which usually coincides with the peak of acute hepatitis B.
Course features:
- Incubation period: 6–10 weeks.
- Pre-icteric period: 5–7 days. Begins acutely: pronounced intoxication, fever above 38°C, migrating arthralgia, and pain in the right upper quadrant due to Glisson's capsule distension.
- Icteric period: Has a characteristic biphasic nature. The first wave (18–32 days) is accompanied by hepatosplenomegaly, rising bilirubin, and aminotransferase activity. Then comes a period of apparent well-being, followed by the second wave with a repeated enzyme spike and liver enlargement.
In 10% of patients, the second wave occurs without jaundice. At this point, the surface antigen (HBsAg) may be eliminated, but anti-HBc IgM and anti-HDc IgM are detected. In 75% of cases, coinfection ends in complete recovery, although in 5–25% of patients, a fulminant form with hepatic encephalopathy and a fatal outcome may develop.
Superinfection: infection against the background of chronic hepatitis B
Occurs when the delta virus infects a person who is already a carrier of HBsAg. Since there is already a high concentration of "building material" in the blood, HDV immediately penetrates the cells and begins aggressive replication.
Clinical picture:
- Incubation and prodrome: Sharply shortened. Incubation takes no more than 3–4 weeks, and the pre-icteric period lasts only 1–3 days with a violent manifestation.
- Multi-wave course: Each successive wave of jaundice and enzymatic exacerbation is more severe than the previous one.
- Progressive course: Occurs in 25–27% of cases. Accompanied by massive liver necrosis and the "empty right upper quadrant" sign (rapid decrease in organ size).
The prognosis for superinfection is unfavorable. In approximately 70% of cases, the disease transitions into a severe chronic form with the rapid development of cirrhosis, and in 30%, a fatal outcome occurs.
Laboratory differential diagnosis
Diagnosis is based on searching for specific markers in serum and assessing the enzymatic profile:
- Biochemistry: Characterized by the predominance of AST over ALT (de Ritis ratio > 1). There is a sharp drop in liver protein-synthetic function indicators (decrease in prothrombin index and sublimate test), which can clinically lead to edema-ascites syndrome.
- Serology (ELISA): In the acute phase, HDAg and early anti-HDV-IgM antibodies are detected against the background of HBV infection markers. During chronization, anti-HDV-IgG begin to dominate.
- PCR: Quantitative and qualitative determination of viral RNA confirms its active replication.
Bradycardia, which is often recorded in the objective status of patients in the icteric period (e.g., heart rate of 60 bpm), is a consequence of the vagotonic action of bile acids accumulated in the blood during cholestasis.
Briefly: answers to topical questions
What is the mechanism of the cytotoxic action of hepatitis D virus on hepatocytes?
Unlike many other hepatotropic viruses, hepatitis D virus possesses direct cytotoxicity, directly destroying infected hepatocytes. In coinfection, liver cell damage is of a mixed nature: the direct cytopathic effect of HDV itself is superimposed on immune-mediated cytolysis induced by HBV. In superinfection, the role of HBV in liver damage becomes minimal, and the clinical picture is exclusively due to the action of HDV.
What genotypes of hepatitis D virus exist and for which regions are they endemic?
There are three genotypes of hepatitis D virus. In Russia, the HDV-1 genotype predominates. In Russia, the highest infection rates have historically been registered in endemic regions — the republics of Tuva and Sakha (Yakutia). Globally, HDV is widespread everywhere, but unevenly.
How is specific prevention of hepatitis D virus infection carried out?
Since hepatitis D virus is defective and requires the presence of hepatitis B surface antigen (HBsAg) for replication, the most effective measure for HDV prevention is widespread population vaccination against hepatitis B. Immunity to HBV automatically protects against HDV infection.
How to remember outcomes: Coinfection — Short (recovery occurs in 75%). Superinfection — Severe and Persistent (70% chronization and cirrhosis, frequent massive necrosis).
Class and exam questions
Why might HBsAg disappear during the second wave of coinfection?
The delta virus suppresses the replicative activity of the hepatitis B virus. This leads to a decrease in HBsAg synthesis, which ultimately deprives HDV of building material and leads to the elimination of both pathogens.
Are there cases of reinfection with delta infection?
No. After recovering from the infection, persistent post-infection immunity is formed. In clinical practice, cases of reinfection with HDV have not been described.
Is HDV transmitted from mother to child?
The perinatal transmission route in HDV infection is implemented much less frequently than in isolated hepatitis B. This explains the low incidence of delta hepatitis in childhood.
What else to study on this topic
- Rolling-circle RNA replication mechanism
- HDV epidemiology: correlation with HBsAg carriage and endemic regions of Russia
- Pathogenesis of pain syndrome: the role of Glisson's capsule in hepatomegaly
- Dynamics of serological markers across coinfection periods
- Principles of diagnosing hepatic encephalopathy in a fulminant course
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