Hepatitis B virus (HBV) is one of the most common infectious microorganisms. It is known that 400 million people in the world have chronic HBV infection. HBV is 100 times more contagious than HIV (Human Immuno Deficiency Virus), which causes AIDS (Acquired Immuno Deficiency Syndrome) in humans. Although hepatitis B is common in the world, the frequency of HBV virus carrier varies by region;
– China 125 million
– Korea 2.6 million
– Japan 1.7 million
– Brazil 3.7 million
– Italy 0.9 million
– USA >1 million
– Turkey 4-5 million (5% in the West, 8-10% in the East)
HOW IS HBV TRANSMITTED AND HOW CAN ITS SPREAD?
HBV is transmitted through the blood and body fluids of people infected with this virus. HBV can survive for 7-10 days in dry environments outside the human body. The mode of transmission varies by region. For example, in parts of China, Southeast Asia, the Middle East and Africa, and South America, transmission is mostly mother-to-baby (Vertical transmission), while in parts of Western Europe, North America, Australia and South America, parenterally (contaminated needle and other medical injections and other interventions with materials, blood transfusion, unprotected sexual intercourse, etc.) transmission is more common (Horizontal transmission). Due to routine screening of donated blood for HBV in blood banks, the risk of HBV transmission due to blood transfusion has been greatly reduced. Transmission routes and risk groups of HBV are shown in the table below.
Since hepatitis B virus is a highly contagious virus, some special precautions must be taken to prevent its spread. The vaccine developed against HBV is still in use and provides lifetime protection if repeated at regular intervals. Vaccination of infants, children and unvaccinated youth and people in the above-mentioned risk group is an appropriate approach. Today, hepatitis B vaccine is routinely given to newborns. Unvaccinated persons exposed to HBV may receive an injection of hepatitis B immune globulin within the first two weeks (passive immunization). This application provides a protection that can last up to 3-6 months. Pregnant women should have the necessary tests for HBV before delivery. In order to prevent transmission and spread, people infected with HBV should maintain a safe sex life (like using a condom), not donate blood, organs, sperm, eggs, and should not share their belongings such as toothbrushes and shaving razors in their daily lives. Plates, spoons, forks, etc. It is unnecessary to use the items separately, provided that they are well cleaned. Practically, 1/10 diluted bleach can be used for cleaning surfaces and materials that are thought to be contaminated with HBV.
COURSE OF HBV INFECTION
After HBV enters the body by any means, it reaches the liver, settles there and begins to multiply in the liver cells. The body’s response to HBV varies according to the age at which the virus was acquired. Disease symptoms in adults usually appear 2-6 months after exposure to the virus. In 60% of adults infected with HBV, the disease is silent without causing symptoms or is usually passed as a mild flu-like infection or a period of fatigue and weakness. In another part of the patients, it may manifest itself as a disease that lasts for 1-2 weeks, requires bed rest and goes with jaundice. During this time, liver enzymes (AST / ALT) are found to be high. The signs of the disease are less pronounced in children than in adults, and there are almost never any symptoms in infancy. In a very small part of the patients (1%), the disease may occur as a serious picture called fulminant hepatitis, and 80% of these patients die. In most of the adults (90-95%) infected with HBV, recovery is achieved by clearing the virus from the body thanks to the immune system, and the rate of chronicity in adults is around 5-10%. In the majority of patients with chronic hepatitis B, the disease is silent and there is no previous history of jaundice. Despite this, the disease becomes chronic in the majority of patients (90% and 10-30%, respectively) after HBV removal in the neonatal and childhood (<5 years) age.
CHRONIC HEPATITIS B
In people infected with HBV, chronic HBV infection is mentioned when HBV is not cleared from the body within 6 months. Mostly, the disease is silent at this stage and almost all of the patients pass into this period without being aware of it. When liver damage increases and liver functions begin to deteriorate, symptoms such as weakness, joint and muscle pain, nausea, yellowing of the whites of the eyes and skin, swelling in the feet and abdomen occur, it is understood that they are infected with HBV as a result of a blood test performed for another reason or by consulting a physician. Chronic HBV infection may progress with different clinical pictures such as asymptomatic HBV carrier, chronic active hepatitis that may end with liver cirrhosis, or development of liver cancer. In 15-25% of patients with chronic liver disease, the cause of death is hepatitis B virus-related liver diseases (See, liver cirrhosis).
When HBV enters the body and settles in the liver, it does not directly cause damage to the liver. As a result of the body’s immune response to the virus (the immune system’s response to the virus), liver cells are damaged. As the virus multiplies inside the liver cell, more immune response occurs, which means more liver cells are damaged. Over time, connective tissue begins to form in place of damaged cells (fibrosis), and liver cirrhosis is the result of widespread connective tissue formation in the liver. Active replication of the virus in the liver is an important risk factor for liver damage. Liver damage is more serious in patients with high levels of virus in the blood.
Sometimes, HBV can acquire a different structure (viral mutation) by undergoing some genetic changes during the proliferation period in the liver. This change may occur during the natural course of chronic HBV infection or may occur after the use of certain drugs for treatment. This is a condition that can change the course of the liver disease and complicates the response to treatment. One of the most common mutations is the HBeAg (Hepatitis B early antigen-Hepatitis B e antigen) mutation. In non-mutated patients, HBeAg production is associated with active replication of the virus. The formation of antibodies against HBeAg in the body (HBeAb or anti-HBe) (Hepatitis B e antibody) is accepted as an indication that the virus has stopped multiplying and the body has started to become immune to HBV, and this event is called ‘seroconversion’. In the presence of mutated HBV infection, active virus replication continues even though HBeAg is not detected in the blood and HBeAb is present. This condition occurs in 30 to 80% of chronic HBV infections in southeast Europe and Asia and is usually associated with childhood HBV infection.
In practice, it is often assumed that HBeAg negative chronic HBV muscles are mistakenly seroconverted (formed antibodies to HBeAg). Patients with seroconversion are generally called inactive carriers and it is accepted that the inflammation in the liver slows down or stops in these patients. In contrast, patients with HBeAg-negative (and HBeAb-positive) mutant chronic HBV infection persist, albeit at a low level, of viral replication and chronic inflammation in the liver progresses. These patients continue their lives as candidates for all kinds of damage that HBV may cause in the liver. In 2/3 of the patients with chronic HBV infection living in Asia, serious complications such as liver cirrhosis and liver cancer occur in the period after HBeAb formation. By measuring the HBV-DNA level in the blood of HBeAg negative and HBeAb formed patients, it can be understood to some extent whether the event is an active mutant virus infection or an inactive disease with seroconversion. Although high HBV-DNA levels are usually indicative of mutant HBV infection, this rule may not always apply. Patients with HBeAg negative mutant HBV infection do not show any disease-related symptoms for years, and the average time it takes for liver cirrhosis to appear in these patients is around 40 years. After the onset of signs of cirrhosis, 25% of patients enter the stage of end-stage liver disease within 10 years.
TREATMENT IN CHRONIC HBV INFECTION
The aim of chronic HBV treatment is to reduce the amount of virus in the body (HBV-DNA <100,000 copies/ml in the serum), to reduce liver enzyme levels to normal levels, to negate the HBe antigen (HBeAg) and to reduce inflammation in the liver. to reduce its severity. Theoretically, reducing the amount of virus slows the progression of the disease in the liver by reducing the immune system activation that causes damage to liver cells. Seroconversion is the disappearance of the HBe antigen (HBeAg) and the formation of antibodies against this antigen (HBeAb). Spontaneous seroconversion occurs at a rate of 1% per year in patients with chronic HBV infection. The opposite is also true. That is, in patients with inactive HBV carriers, the disease can turn into an active form at a rate of 1% per year. The occurrence of seroconversion is accompanied by the decrease in the amount of virus (HBV-DNA) in the body to levels that can only be measured by some special tests such as PCR, normalization of liver function tests and regression of signs of inflammation in the liver. Interferon, lamivudine, adefovir, and entacavir are three drugs that are currently accepted and used to be effective in the treatment of chronic HBV infection. Apart from these, there are other antiviral drugs that have not been put into routine practice yet but are expected to be used in the coming years (telbivudine, emcitarabine, etc.). Although the permanent response after this treatment depends on the type of virus, unfortunately it is still around 30% (25-39%). In addition to drug therapy, patients with chronic HBV infection should definitely not drink alcohol and consult a doctor before using drugs that may be harmful to the liver.
MINI DICTIONARY
ALT (Alanine aminotransferase): An enzyme made in the liver. Viral, toxic, ischemic, etc. of liver cells. Its level in the blood increases after it is damaged due to reasons. Its normal value is < 40 IU/L.
AST (Aspartate aminotransferase): An enzyme made in the liver. An increased level in the blood may be a sign of liver cell damage. Its normal value is < 40 IU/L.
Albumin: A protein made in the liver that prevents the leakage of fluid from the capillaries into the tissues and enables the transport of many substances in the blood. When the blood level decreases as a result of liver or kidney diseases, edema and ascites occur as a result of fluid accumulation in the body cavities and legs. Normal serum level is 3.5-4.5g/gl.
Alkaline phosphatase (Alkaline phosphatase): An enzyme made in the liver, bone, intestines and placenta. The serum level may be elevated in liver and biliary tract diseases. Its normal value is < 112 IU / L.
Alpha-fetoprotein: A protein secreted from cancer cells. In liver cancer (Hepatocellular carcinoma), it reaches very high levels in the blood.
Antibody (Antibody – ab): Substances in protein structure formed by the body’s immune system against foreign substances (proteins, chemicals, toxins, viruses, bacteria, etc.) entering the body. Antibodies formed after infection or vaccination protect the body against similar infections that will be encountered later.
Antigen (Antigen – ag): Protein-containing substances found on the surface of bacteria, viruses or different cells and stimulating the body’s immune system to form antibodies.
Bilirubin: A yellow pigment (dying substance) that emerges as a result of the breakdown of red blood cells (Red blood cells). When liver functions are impaired, its level in the blood rises, causing yellowing of the whites of the eyes and skin, and darkening of the color of the urine. The normal serum level is <1.2mg/dl.
Biopsy (Liver biopsy): Taking a piece of the liver with a thin needle to determine the degree of liver damage. Usually, the patient does not need to stay in the hospital for this procedure and is performed under local anesthesia.
ccc DNA (Covalently Closed Circular DNA): The part of HBV DNA that makes multiple copies in the nucleus of the infected liver cell and plays a key role in the replication of the virus inside the liver cell. It is investigated in tissue samples taken by liver biopsy. Clearance of ccc DNA from liver cells is theoretically accepted as an indication that the liver is cleared of HBV.
Core antibody (Core antibody- HBcAb or anti-HBc): A protein formed by the body’s immune system and showing the presence of current or past infection due to HBV.
Core antigen (Core antigen – HbcAg): Protein that forms a shell around HBV DNA.
DNA polymerase: An enzyme required for HBV DNA replication
Decompensated cirrhosis: Late stage of liver cirrhosis. Disorder of liver function tests and swelling in the abdomen, legs, blood clotting disorders, bleeding, etc. and with other complications.
Liver transplantation is considered in decompensated cirrhosis.
e antigen (HBeAg): A protein formed during active replication of HBV. The presence of HBeAg positive in the blood indicates that the virus is actively multiplying.
e antibody (HBeAb or anti-HBe): It is an antibody made by the immune system temporarily during acute HBV infection or during the course of chronic HBV infection (See antibody). The disappearance of e antigen (HBeAg) and formation of e antibody (anti-HBe) in patients receiving antiviral treatment is called seroconversion and is an indication of a long-term response to treatment.
Fibrosis: Formation of connective tissue (scar tissue) after chronic infection and inflammation (inflammation). In liver cirrhosis, there is extensive fibrosis formation in the liver.
GGT (Gamma-glutamyl transferase): An enzyme whose blood level may increase in liver and biliary tract diseases. Although not typically elevated in the course of HBV infection, serum levels may increase when liver cirrhosis or liver cancer occurs in the course of chronic HBV infection. Its normal value is <60 IU/L.
HBV- DNA (Deoxyribonucleic acid): The nucleic acid that controls the production of HBV. Detection of high amount of HBV in serum (>105) indicates the presence of active viral replication. It is used to evaluate the response to antiviral therapy.
Liver enzymes: Different proteins (ALT, AST, GGT, Alkaline phosphatase, etc.) that catalyze chemical reactions that play a role in metabolic events in the body. When liver cells are damaged for any reason, after these enzymes pass into the bloodstream, their levels in the blood increase and they help in the diagnosis of liver diseases.
Coagulation factors: Protein-structured substances that enable blood to clot and are made in the liver. In liver cirrhosis and acute liver failure, spontaneous bleeding occurs due to the deficiency of these factors, or bleeding from other causes becomes difficult to stop.
Prothrombin time: It is a test that measures the functions of coagulation factors (blood clotting ability) made in the liver. In liver cirrhosis or acute liver failure, the prothombin time is prolonged due to the insufficiency of coagulation factors. Its normal value is <14sec.
Seroconversion: Conversion from Antigen positive / Antibody negative to Antigen negative / Antibody positive. Seroconversion of HBsAg (Hepatitis B surface antigen) to anti-HBs (Hepatitis B surface antibody) is accepted as an indication that the virus has been completely cleared from the body and lifelong immunity has been established.
Cirrhosis: Irreversible connective tissue formation in the liver after chronic inflammation. Liver functions are impaired in cirrhosis and various symptoms occur due to these (See. Liver cirrhosis)
Surface antigen (HBsAg) (Hepatitis B surface antigen): A protein made in the liver infected with HBV. When surface antigen, e antigen and HBV-DNA are detected in the blood, the patient is considered highly contagious. Its presence in the blood indicates acute infection, HBV carrier or chronic HBV infection.
Surface antibody (HBsAb or anti-HBs) (Hepatitis B surface antibody): Protein (antibody) produced by the body’s immune system against the surface antigen of the virus after infection or vaccination with HBV. The disappearance of HBsAg (Hepatitis B surface antigen) and the emergence of anti-HBs is accepted as an indication that the virus has been completely cleared from the body and lifelong immunity has been established.
