Hepatitis B. Symptoms, diagnosis, consequences and treatment.

Key Facts

• Hepatitis B is a viral infectious disease that affects the liver and occurs in acute or chronic form.
• Transmission of the virus most often occurs perinatally from mother to child, as well as through contact with blood or other biological fluids, in particular during sexual contact with an infected partner, unsafe injection practices, cuts with piercing instruments in medical practice and in domestic conditions, and also among people who inject drugs.
• WHO estimates that in 2021, there were 296 million people worldwide living with chronic hepatitis B (i.e. positive for hepatitis B surface antigen).
• An estimated 820,000 people died from hepatitis B in 2021, primarily as a result of hepatitis-related liver cirrhosis and hepatocellular carcinoma (primary liver cancer).
• As of 2021, 30.4 million (10)% of all people living with hepatitis B were aware of their infection, and 6.6 million (22%) of all diagnosed patients were receiving treatment. According to the latest WHO estimates, in 2021 the proportion of children under five years of age with chronic hepatitis B has fallen to just under 1%, compared with the decades before the introduction of vaccination (i.e. from the 1980s to the early 2000s). x years) this figure was about 5%.
• According to WHO estimates, in 2021, despite the availability of a highly effective vaccine, the number of people primarily infected with hepatitis B was about 1.5 million people.
• Hepatitis B is preventable through safe, accessible and effective vaccines.

Hepatitis B is a potentially life-threatening infectious liver disease caused by the hepatitis B virus (HBV). This disease is a major health problem worldwide. The infection can become chronic with a high risk of death from cirrhosis and liver cancer.

There is a safe and effective vaccine that provides 98–100% protection against hepatitis B. Prevention of viral hepatitis B helps prevent the development of complications such as chronic hepatitis and liver cancer.

Mechanisms of transmission

In highly endemic areas, hepatitis B is most often transmitted either from mother to child during childbirth (perinatal transmission) or through horizontal transmission (contact with infected blood), especially between infected and uninfected children in the first five years of life. Infants who are infected from their mother, or children who become infected under 5 years of age, very often develop chronic infection.

Hepatitis B is also transmitted through needle sticks, tattoos, body piercings, and contact with infected blood and body fluids, including saliva, menstrual and vaginal fluids, and semen. Infection can also occur through the reuse of contaminated needles and syringes or sharps in medical institutions or in domestic settings, as well as among people who inject drugs. Infection can be transmitted through medical, surgical and dental procedures, tattooing, and the use of razor blades and similar devices contaminated with infected blood. In addition, the hepatitis B virus can be transmitted through sexual contact, especially among unvaccinated individuals who have multiple sexual partners.

Chronic hepatitis B develops in less than 5% of people infected as adults, and in about 95% of those infected during infancy and early childhood. The hepatitis B virus can survive outside the human body for at least seven days. During this period of time, the virus retains the ability to cause infection if it enters the body of an unvaccinated person. The duration of the incubation period for hepatitis B ranges from 30 to 180 days and averages 75 days. The virus is detected in the blood within 30–60 days after infection and can persist in the body, causing chronic hepatitis B, especially if infected during infancy or childhood.

Vaccines

Expert opinion

CM. Harit

Professor, Doctor of Medical Sciences, Head of the Department of Prevention of Infectious Diseases, Research Institute of Children's Infections
Hepatitis B is contracted everywhere equally through blood (everyone) and through sexual contact (teenagers and adults). A drop of blood is so small that you cannot see it and it is already contagious, so families become infected through toothbrushes, razors, etc...

The basis for preventing hepatitis B is vaccination. WHO recommends that all infants should receive hepatitis B vaccine as soon as possible after birth, preferably within 24 hours. If a child does not receive this vaccination in the maternity hospital, the risk of infection increases significantly, and if a newborn is infected during the neonatal period, liver cirrhosis develops in adolescence or early adulthood.

The dose given at birth should be followed by two or three subsequent doses to complete the vaccination series. In most cases, one of the following two options is considered optimal:

• A three-dose hepatitis B vaccination regimen, in which the first dose (of monovalent vaccine) is given at birth and the second at 1 month of age, which is also very important, since this dose minimizes the risk of infection of the child from infected family members. The third dose (of monovalent or combination vaccine) is administered at 6 months, simultaneously with the DTP vaccine, which determines the duration of immunity against hepatitis B.
• A four-dose regimen in which the first dose of monovalent vaccine given at birth is followed by 3 doses of monovalent or combination vaccine, usually given along with other vaccines as part of routine childhood immunization, is indicated for children born to mothers infected or with hepatitis B.

After a full series of vaccinations, more than 95% of infants, children of other age groups and young adults develop protective antibody levels. Protection lasts for at least 20 years and possibly a lifetime.

More about vaccines

Symptoms

In most cases, the primary infection is asymptomatic. However, some patients experience acute symptoms with severe symptoms that persist for several weeks and include icteric discoloration of the skin and sclera, dark urine, severe weakness, nausea, vomiting and abdominal pain. In rare cases, acute hepatitis can lead to acute liver failure with a risk of death.

In some people, the hepatitis B virus can also cause a chronic liver infection, which over time can develop into cirrhosis (scarring of the liver) or liver cancer.

Who is at risk for chronic hepatitis B?

The likelihood of developing a chronic infection depends on the age at which a person became infected with the hepatitis virus. Chronic infection is most likely to develop in children infected with the hepatitis B virus before the age of six.

Infants and young children:

• in infants infected in the first year of life, chronic infection develops in 80–90% of cases;
• Children infected before the age of six develop chronic infection in 30–50% of cases.

Adults:

• in people infected with hepatitis B as adults, in the absence of other concomitant diseases, chronic infection develops in less than 5% of cases;
• if chronic infection develops in 20–30% of adults, the disease leads to cirrhosis and/or liver cancer.

Effectiveness of vaccination

As of 2013, 183 Member States were vaccinating infants against hepatitis B as part of their national vaccination schedules, and 81% of children had received hepatitis B vaccination. This represents significant progress compared to 31 countries in 1992, when the World Assembly Health Council adopted a resolution recommending global vaccination against hepatitis B.

Additionally, as of 2013, 93 Member States have introduced hepatitis B dose provision at birth. Since 1982, more than one billion vaccine doses have been used worldwide.

In many countries where typically 8% to 15% of children had chronic hepatitis B virus infection, vaccination has reduced rates of chronic infection among immunized children to less than 1%.

Diagnostics

Based on the clinical picture alone, it is impossible to differentiate between hepatitis B and other types of viral hepatitis; Therefore, laboratory confirmation of the diagnosis is extremely important. Several laboratory blood testing methods are available to diagnose and monitor patients with hepatitis B. They can be used for differential diagnosis of acute and chronic infections.

Methods for laboratory diagnosis of infection include detection of hepatitis B surface antigen (HbsAg). To ensure blood safety and prevent accidental transmission of the virus to recipients of blood products, WHO recommends systematic testing of donated blood for hepatitis B.

• Acute HBV infection is characterized by the presence of hepatitis B virus surface antigen (HBsAg) and antibodies to core antigen (HBcAg) - class M immunoglobulins (IgM). During the initial phase of infection, patients also develop hepatitis B virus e antigen (HbeAg). HBeAg is usually a marker of high levels of viral replication. The presence of HBeAg indicates the highly contagious nature of the blood and biological fluids of the infected person.
• Chronic infection is characterized by the persistence of HBsAg for at least six months (with or without the simultaneous presence of HBeAg). The persistent presence of HBsAg is a major marker of the lifetime risk of developing chronic liver disease and liver cancer (hepatocellular carcinoma).

Sources

1. Hepatitis B. World Health Organization.
2. J. Feld (Canada) and HLA Janssen (Canada/Netherlands). Hepatitis B. Global Practical Recommendations of the World Gastroenterological Organization. — February, 2015.
3. Information page about the hepatitis B virus. State of Israel, Ministry of Health.
4. Viral hepatitis B: symptoms, treatment, prevention. GBUZ "Specialized Clinical Infectious Diseases Hospital" of the Ministry of Health of KK.
5. Hepatitis B. Wikipedia.
6. Acute and chronic viral hepatitis in the practice of a local physician. State budgetary educational institution of higher professional education "Ivanovo State Medical Academy" of the Ministry of Health of the Russian Federation. — 2015.
7. Order of the Ministry of Health of the Russian Federation dated March 21, 2014 N 125n “On approval of the national calendar of preventive vaccinations and the calendar of preventive vaccinations for epidemic indications” (with amendments and additions).

Treatment

There is no specific treatment for acute hepatitis B. Therefore, medical care focuses on maintaining physical comfort and proper nutritional balance, including replacing fluid losses caused by vomiting and diarrhea. It is very important to avoid unnecessary drug treatment. Acetaminophen/paracetamol and antiemetics should not be prescribed to patients with hepatitis A.

For chronic hepatitis B, drug treatment may be prescribed, including oral antiviral drugs. Treatment can slow down the development of liver cirrhosis, reduce the risk of developing liver cancer and increase long-term survival rates for patients. WHO estimates that in 2021, 12 to 25% of people with chronic hepatitis B will need drug treatment (depending on conditions and selection criteria).

WHO recommends prescribing the oral drugs tenofovir and entecavir, which are the most effective drugs for suppressing the replication of the hepatitis B virus. Their use less often leads to the formation of drug resistance, is simple (1 tablet per day) and is not accompanied by significant side effects, and therefore there is no the need for careful monitoring of patients.

Entecavir is not a branded drug. In 2017, all low- and middle-income countries were able to legally purchase generic entecavir, although costs and availability varied widely. Tenofovir is no longer protected by patent in any country in the world. In 2021, the international median price of WHO prequalified generic tenofovir decreased from US$208 to US$32.

For most patients, drug treatment effectively suppresses viral replication but does not completely cure hepatitis B. Therefore, most patients who start treatment for hepatitis B must continue it for life.

In many resource-poor areas, access to hepatitis B diagnosis and treatment remains difficult. In 2021, of the more than 296 million people living with HBV, only 10% (30.4 million) knew of their diagnosis. Only 22% (6.6 million) of diagnosed patients were treated. Many patients are diagnosed in the later stages of liver disease.

Among the chronic complications of hepatitis B, high rates of morbidity and mortality are associated with advanced liver diseases such as cirrhosis and hepatocellular carcinoma. Liver cancer progresses rapidly and, given the limited treatment options, the outcome is usually poor. In low-income countries, most patients with liver cancer die within a few months of diagnosis. In high-income countries, the lives of such patients can be extended by several years through surgery and chemotherapy. Also in high-income countries, some patients with cirrhosis or liver cancer receive liver transplantation, but success rates for such treatment are variable.

Prevention

The main method of preventing hepatitis B is vaccination. WHO recommends that all newborns be vaccinated against hepatitis B as soon as possible after birth, within the first 24 hours of life if possible, followed by two or three doses of the vaccine at least four weeks apart to ensure full vaccination. Timely vaccination of children immediately after birth is an effective way to reduce the incidence of mother-to-child transmission of hepatitis B.

According to the latest WHO estimates, worldwide in 2021 the proportion of children under five years of age with chronic hepatitis B has fallen to just under 1%, compared with the decades before the introduction of vaccination (i.e. from the 1980s to early 2000s) this figure was about 5%.

This has achieved one of the Sustainable Development Goal targets for viral hepatitis elimination: reducing the prevalence of HBV infection among children under five years of age to less than 1% by 2021. This success was achieved in a number of regions with the exception of sub-Saharan Africa.

Increasing hepatitis B vaccination coverage worldwide over the past two decades has been a major public health achievement and has contributed to a decline in the incidence of hepatitis B infection among children.

In 2021, three-dose vaccine coverage reached 85% worldwide, up from around 30% in 2000. However, rates of newborn immunization against hepatitis B remain variable. Thus, the average rate of vaccination coverage with the first dose of hepatitis B vaccine immediately after birth is 43% worldwide, but in the WHO African Region it is only 6%.

A full course of vaccination produces protective antibodies in more than 95% of infants, children and young adults. Immunity acquired through vaccination lasts for at least 20 years and probably throughout life. Therefore, WHO does not recommend booster vaccinations for people who have completed the three-dose vaccine.

In countries with low or moderate endemicity of hepatitis B, vaccination is indicated for all unvaccinated children and adolescents under 18 years of age. In these countries, high-risk groups are more likely to become infected and should also be vaccinated. These risk groups include:

• individuals who frequently require blood or blood products, dialysis patients, and solid organ transplant recipients;
• prisoners in places of deprivation of liberty;
• injection drug users;
• persons who have household and sexual contact with people with chronic HBV infection;
• persons with multiple sexual partners;
• healthcare workers and other persons who may have contact with blood and blood products while on duty;
• International travelers who have not completed a full course of HBV vaccination and who are eligible for vaccination before departure to HBV-endemic areas.

The vaccine has an excellent safety and efficacy record and has reduced the proportion of children under five years of age with chronic HBV infection to just under 1% in 2021, compared with the decades before the introduction of the vaccine (i.e. since the 1980s). until the early 2000s), this figure was about 5%.

In addition to infant vaccination, which includes a timely first dose immediately after birth, WHO recommends prophylactic antiviral therapy to prevent mother-to-child transmission of hepatitis B. Pregnant women with a high concentration of HBV DNA (high viral load) and/or the presence of HBeAG in the blood are at high risk of transmitting the virus to their unborn child, even if the child receives the first dose of vaccine immediately after birth and completes the full course of vaccination against hepatitis B. Therefore, pregnant women with high The concentration of HBV DNA during pregnancy may indicate a prophylactic course of antiviral therapy to prevent perinatal HBV infection and protect the unborn newborn from the disease.

In addition to infant vaccination and prevention of mother-to-child transmission, HBV transmission can be prevented through blood safety measures, including quality screening of all donated blood and blood products used for transfusion. Globally, 97% of donated blood units were screened and quality controlled in 2013, but gaps remain. Effective measures to prevent the transmission of hepatitis B virus include ensuring safe injections and avoiding unnecessary injections and injections performed in unsafe conditions. Between 2000 and 2010, the rate of unsafe injections worldwide fell from 39% to 5%. In addition, one of the effective measures to prevent infection is to improve the safety of sexual intercourse, including minimizing the number of sexual partners and the use of barrier contraception (condoms).

How is hepatitis B transmitted?

The pathology in humans is caused by one of the representatives of the hepadnavirus family, the hepatitis B virus (HVB). At the same time, not only people with acute and chronic forms of hepatitis B become sources of infection, but also so-called “healthy virus carriers” - people who do not have signs of the disease, but have the virus in their blood.

Are there no healthy carriers of the hepatitis B virus?

According to modern ideas about viral hepatitis B, the term “healthy virus carriers” must be removed from medical terminology.
Previously, this was the name given to people without manifestations of liver disease, in whose blood the hepatitis B virus was detected for more than 6 months. However, this term cannot be called accurate - after six months of virus carriage, chronic hepatitis B can already be diagnosed. Despite the absence of symptoms and manifestations of the disease, the liver of such patients can irreversible changes occur, which in 25% of cases ends in death due to cirrhosis or organ cancer. Therefore, it is impossible to unequivocally call them “healthy” - this can lead to a false belief about the safety of this form of carriage of the virus. Also, “carriers” pose a risk to truly healthy people - they can infect others with the hepatitis B virus. Thus, the term “healthy carrier” leads to misperception of this form of viral hepatitis B and can lead to an irresponsible attitude towards one’s own health or the well-being of others. Although the main route of transmission of infection in the case of hepatitis B is contact with infected blood, it is important to remember that HVB is found in all biological fluids of the patient:

• blood;
• urine;
• vaginal secretion;
• tear fluid;
• saliva;
• sperm;
• breast milk.

Hepatitis B is transmitted from one person to another mainly through contact with blood and semen. Other biological fluids pose practically no serious danger in epidemiological terms, since the concentration of the virus in them is low and is considered insufficient for infection.

The contagiousness (ability to cause infection) of the hepatitis B virus is high. It is also a virus with high resistance in the external environment. Outside the human body on various surfaces at room temperature, it is able to maintain its viability for 7-10 days. During this time, the virus poses a danger.

Important! Hepatitis B is not spread by airborne droplets (coughing, sneezing), by kissing, hugging, sharing utensils, through water and food, or insect bites.

Routes of infection

For a person to become infected, the virus must enter his or her bloodstream. But not only direct contact with wound surfaces can lead to infection. Penetration occurs in a variety of ways, so it is important to be aware of each (Figure 1).

Figure 1. Routes of transmission of hepatitis B. Source: ann131313 / Depositphotos

Parenteral route

Previously, viral hepatitis B was called serum hepatitis - this is due to the fact that a person was infected mainly as a result of infected blood serum entering his body. These types of transmission have occurred through the use of reusable medical products.

Currently, the likelihood of human infection during medical procedures, including blood transfusions, is minimized. This is facilitated by:

• use of disposable medical instruments;
• organization of centralized sterilization departments in medical institutions;
• mandatory screening of blood donors for hepatitis B virus carriage.

The parenteral route of infection (the penetration of the virus from the blood of an infected person to a healthy person) is more often observed today with insufficient disinfection of instruments for dental treatment, manicure or pedicure, or the repeated use of needles for piercing or tattoos.

Hepatitis B is also widely spread among injection drug users when using the same needle and not following safety rules for the transmission of viral infections.

Important! The combination of viral hepatitis B and HIV infection is not uncommon. Among HIV-infected people, approximately 7.4% are also infected with the hepatitis B virus. Treatment of such patients is simplified by the fact that combination therapy for HIV infection includes a drug that is highly active against the hepatitis B virus.

Sexual tract

Due to frequent damage to the external genitalia during intimate contact, parenteral transmission of hepatitis B is also possible.

The risk of contracting the infection is increased by promiscuous intimate relationships, homosexual contacts in men, and sexual contacts with representatives of the sex industry.

Vertical path

The virus can also be transmitted from a mother to her newborn child - this is a vertical route of spread.

During a normal pregnancy, the hepatitis B virus cannot cross the placental barrier, so the unborn child is safe. But if the placenta is damaged, the virus penetrates the fetus and infects it. The risk of transmission of infection increases if in the last months of pregnancy the expectant mother develops acute hepatitis or the activity of the virus increases significantly.

Also, transmission of the virus can occur during childbirth when the baby comes into contact with the mother's blood. This type of infection most often leads to the development of hepatitis B in children, since in the absence of preventive measures the mother has a 70–90% chance of transmitting the infection to her child during childbirth [1].

The concentration of the virus in breast milk is low, so breastfeeding is not contraindicated for women with chronic hepatitis B. However, if an infected woman develops bleeding nipple cracks, the child should be switched to artificial nutrition until the wounds are completely healed.

Important! The danger of infection with hepatitis B in infancy and early childhood is that in 95% of such cases the pathology becomes chronic, causing severe complications and often leading to death.

Household way

Failure to comply with personal hygiene measures is one of the common causes of infection transmission in families, as well as in organized children's groups. The greatest danger is the use of shared manicure accessories, razors, and toothbrushes. If there are damages to the skin and mucous membranes of a healthy person (abrasions, cuts, abrasions, diaper rash), their contact with objects contaminated with the secretions of a person with hepatitis B can cause infection.

Classification

Hepatitis B can be acute (up to 3 months), subacute (up to six months) and chronic (over 6 months).

Depending on the characteristics of the clinical picture, two forms of acute hepatitis B are distinguished: typical and atypical. The typical form of the pathology occurs with a pronounced icteric period. In the atypical form of the disease, jaundice does not develop or its manifestations are expressed unnoticed both for the person with hepatitis B and for others [6].

In addition, there are 4 forms of acute hepatitis according to the severity of symptoms and severity of the course:

• light;
• moderate;
• heavy;
• malignant (fulminant).

The possible outcome of the disease is: recovery, transition to a chronic form and the development of fatal liver diseases.

Chronic hepatitis B can also have different activity. Depending on this, he distinguishes:

• minimally active form;
• mild form;
• moderate form;
• severe form.