Hepatitis D

Hepatitis D (hepatitis delta, hepatitis B with delta agent) is a viral hepatitis with a contact mechanism of pathogen transmission, caused by a defective virus, the replication of which is possible only in the presence of HBsAg in the body. The disease is characterized by a severe course and an unfavorable prognosis.

Hepatitis D is a type of the HBV (viral hepatitis) group and is called delta infection. The D virus was first differentiated as a separate component in 1977 during an unprecedented outbreak of HBV (virus B) in the countries of Southern Europe. The D virus is considered defective, since it does not reproduce on its own; it requires the presence of HBV to spread. Delta infection (HDV) is resistant to external factors, but can be treated with alkaline or acidic environments. The disease is very severe, since it develops against the background of an existing hepatitis B infection.

Today, Hepatitis D is identified in two forms:

1. As a concomitant infection (co-infection) developing simultaneously with infection with the B virus.
2. As a superinfection that develops after infection with the B virus (HBsAg antigen) as a layering.

The HDV virus has its own RNA genome, is transmitted exclusively by hematogenous means and can only affect those who are already infected with the hepatitis B virus. Such a pathological combination often ends with necrosis of liver cells, cirrhosis.

ICD-10 codes

• 816.0. Acute hepatitis B with delta agent (coinfection) and hepatic coma.
• 816.1. Acute hepatitis B with delta agent (coinfection) without hepatic coma.
• B17.0. Acute delta (super) infection of hepatitis B virus carrier.

Epidemiology of Hepatitis D

HDV is defined as an incomplete, defective virus - a satellite. Possessing only RNA, the virus needs an outer shell for replication. That is why it uses the hepatitis B virus, which has its own DNA. On the one hand, this forms the hepatotropic pathogenic properties of delta infection, on the other hand, it allows it to quickly penetrate into liver cells. Despite the fact that the genotypes of hepatitis delta virus - HDV were identified relatively recently, one of them has already been well studied. Genotype I affects residents of the United States and European countries, the remaining genotypes have not yet been classified.

The epidemiology of hepatitis D (HDV) is characterized by the main route of spread - artificial, most often as a result of injections, medical manipulations. There is also a natural route of infection, which is similar to the spread of hepatitis B. Hepatitis D is not capable of independently provoking hepatitis without self-reproduction of the HBV virus, therefore the combination of HDV and hepatitis B most often ends in liver cirrhosis (70% of infected).

Statistics show that today in all countries of the world there are at least 350 million carriers of the hepatitis B virus, of which about 5 million are infected with delta hepatitis - HDV. The highest percentage of infection is observed in chemically dependent people (drug addiction), it has also been clinically proven that in HIV-infected people the hepatitis D virus quickly reactivates.

The epidemiology of hepatitis D is characterized by territorial endemicity for the population of southern European countries, for some northern states of America and for the countries of South America, where most cases of co-infections are diagnosed, however, in the form of superinfection, hepatitis D is most often found with injection infection everywhere. People with hemophilia and diseases requiring transfusion therapy are also at risk. Among homosexuals who carry the HBsAg genotype, delta hepatitis is rare.

Hepatitis D - Epidemiology

[ 1 ], [ 2 ], [ 3 ], [ 4 ], [ 5 ]

Causes of Hepatitis D

The cause of hepatitis D is human infection with the delta virus (HDV), which is not an independent pathogen. The hepatitis D genotype is not capable of replication without the presence of the hepatitis B virus in the body, since it consists of single-stranded RNA and delta antigen. Self-reproduction in a hepatocyte (liver cell) is possible only in the presence of DNA-containing HBV.

There are two options in the interaction of these two viruses:

Simultaneous penetration into the body or co-infection.

Layering of the hepatitis D virus on the DNA envelope of the hepatitis B virus or superinfection.

If the cause of hepatitis D is the first option, the disease is extremely severe, but modern medicine tries to control it with the help of intensive drug therapy.

The second option is more unfavorable: hepatitis develops quickly, occurs in an acute form and often ends in cirrhosis or carcinoma.

The cause of hepatitis D is that a person, due to pathological diseases or lifestyle, is included in risk groups. The main categories that are at risk of HDV infection are:

• Patients with hemophilia.
• Patients in need of transplantation.
• Chemically dependent people (drug addiction).
• Homosexual relations.
• Children whose mothers are infected (vertical transmission).
• Patients requiring hemodialysis.
• Healthcare workers who, by virtue of their profession, have contact with blood materials.

Hepatitis D - Causes and Pathogenesis

[ 6 ], [ 7 ], [ 8 ], [ 9 ], [ 10 ], [ 11 ], [ 12 ], [ 13 ], [ 14 ]

Symptoms of Hepatitis D

The incubation period of the HDV virus can last from 3 weeks to several months, and the symptoms of hepatitis D depend on the duration of the incubation period. There are two clinically manifested periods - pre-icteric and icteric, which differ little in symptoms from the signs of hepatitis B.

• Acute form of the disease
• The pre-icteric period, which in superinfection (layering) is shorter than in combined, co-infection (lasts no more than 7 days):

1. Gradual decrease in activity, fatigue, drowsiness.
2. Decreased appetite, weight loss.
3. Periodic febrile condition.
4. Chronic feeling of nausea.
5. Subfebrile body temperature.
6. Pain, aches in the joints.

• Jaundice period:

1. Coloring of the skin and sclera of the eyes in a yellow tint (saffron).
2. Light-colored stool (depigmentation).
3. Dark urine (dark beer color).
4. Urticarial rash.
5. A pronounced pain on the right side, in the hypochondrium.
6. Objectively, upon palpation, the liver and spleen are enlarged.
7. Signs of intoxication of the body.
8. Dizziness.
9. Nausea and vomiting.
10. Superinfection is characterized by a sharp increase in body temperature.

Acute hepatitis D rarely ends in complete recovery; even with adequate treatment, it becomes chronic.

Symptoms of hepatitis D, chronic form:

• Gradual yellowing of the skin.
• Hemorrhages are microscopic subcutaneous hemorrhages (asterisks).
• Hepatomegaly, splenomegaly.
• Nosebleeds.
• Increased sensitivity of gums, bleeding.
• Increased vascular permeability, bruising.
• A constant feverish state with a body temperature ranging from 37.5 to 39 degrees without signs of acute respiratory viral infection or acute respiratory disease.
• Ascites, swelling.
• Chronic nagging pain in the right hypochondrium.

Hepatitis D - Symptoms

Diagnosis of hepatitis D

The main diagnostic method for determining HDV is a serological blood test. Diagnostics of acute hepatitis D reveals specific immunoglobulin - anti-HDV-IgM, as well as HD antigen along with the expected markers of hepatitis B. When repeated, the results show a significant increase in IgG titers. Serum shows a significantly elevated level (biphasic) of aminotransferases (ALT, AST).

Diagnosis of chronic hepatitis D determines the presence of specific immunoglobulin anti-HDV-IgM. The polymerase chain reaction (PCR) method confirms the replication (self-reproduction) of the virus when determining the quantitative and qualitative parameters of the RNA of delta infection.

Also, according to indications, a study of the biological material of the liver can be carried out - a biopsy, as a result of which it is possible to identify the RNA of the virus and antigens in cells - hepatocytes. Diagnosis of hepatitis D is necessary for a clear differentiation of the genotype and type of the virus, since the choice of treatment option depends on this.

Hepatitis D - Diagnostics

[ 15 ], [ 16 ]

Treatment of hepatitis D

Treatment of hepatitis D is in three directions:

1. Antiviral treatment (alpha interferon).
2. Symptomatic therapy (hepatoprotectors, enzymes, vitamins).
3. Diet therapy (diet No. 5 according to Pevzner.

The main method of treating HDV is IFN therapy – interferon therapy. Also, treatment of hepatitis D involves basic detoxification, hepatoprotective therapy, which are identical to the therapeutic strategy for infection with the hepatitis B virus.

Treatment of hepatitis D with interferon (alpha-interferon) is the use of fairly large doses of the drug - up to 10,000,000 IU per day. The introduction is carried out every two days (three times a week) for a long time - at least one year. This method allows to reduce symptoms, but the tolerance of intensive interferon therapy in patients with a combined infection is much worse than in the presence of a separate HBV virus.

As a rule, treatment is carried out on an outpatient basis; hospitalization is necessary only for a biopsy or in case of urgent dehydration, detoxification using the infusion method.

Hepatitis D - Treatment

Prevention of hepatitis D

Hepatitis D infection can only be prevented by taking preventive measures to prevent human infection with the hepatitis B virus, since HDV cannot reproduce on its own; it requires HBV DNA. Today, vaccination against hepatitis B is considered to be a fairly reliable guarantee that the human body develops a strong immune defense against HBV and, accordingly, against hepatitis D.

Also, hepatitis D prevention is a whole range of measures aimed at informing the population about the danger of infection. Rules for the sterility of medical instruments, devices, checking the sterility of donor blood, preparations containing biological material, donor biological materials, safe protected sexual contacts are the main measures that help reduce the frequency of hepatitis infections in principle. In addition, people who are already infected with HBV should undergo regular medical examinations and be responsible not only for their own health, but also understand that they are a source of potential infection for others. Hepatitis D prevention is also the prevention of injection infection when using narcotic drugs, but this problem is so global that its description requires a separate information space.

Hepatitis D Vaccination

The main way to prevent HDV infection is through hepatitis D vaccination.

Currently, there is no specific vaccine against the delta virus infection, this is explained by the high degree of reliability of vaccination against hepatitis B. It has been statistically and clinically proven worldwide: those vaccinated against HBV have strong immune protection and antibodies to HBsAg. In addition, even with late vaccination and the presence of the virus in the body, the disease in patients is much easier and has a relatively favorable prognosis.

97% of people who have had hepatitis B or who have been vaccinated against this infection in a timely manner do not become infected with the delta virus. Thus, vaccination against hepatitis D is primarily a routine vaccination against hepatitis B, the first of which is given within 12 hours after birth. Until a vaccine against HDV is created, the only way to avoid infection with the delta virus is timely early vaccinations and adherence to preventive measures.

Hepatitis D prognosis

The prognosis for hepatitis D is especially unfavorable for people suffering from chemical dependency. Injection drug addicts are not only the first risk group, but also the highest percentage of fatal outcomes, which, according to statistics provided by WHO, is about 65%. Mortality is due to the rapid development of liver failure and extensive necrotic processes. Mass necrosis of hepatocytes in combined infection (co-infection) is extremely difficult to stop. In addition, the unfavorable prognosis for hepatitis D is due to the fact that the HDV clinic often manifests itself in the late period against the background of chronic hepatitis B, lasting for years. The delta virus is a trigger factor for the rapid development of an exacerbation, when the necrotic process affects the liver in just a few days.

The prognosis also depends on the course of the disease:

1. Chronic, latent form. In this form, hepatitis can develop over 10 years or more, gradually depleting the body's reserve and protective properties.
2. Rapidly progressing form. The disease develops over 1-2 years.
3. The disease progresses in waves, from 5 to 10 years.

Almost all chronic forms of hepatitis D end in liver cirrhosis.

Oncologic process in patients with hepatitis D is extremely rare, it is obvious that progression of the disease during superinfection or co-infection does not give place and time for development of hepatocellular cancer. Most often, patients die before the process passes to the malignant stage.

The prognosis is most favorable for those who received late vaccination; it helps reduce the severity of symptoms and significantly increases the patient's chances of relative recovery.