Hepatitis B
Hepatitis B is an infectious disease caused by the hepatitis B virus that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection.
Many people have no symptoms after exposure. For others, symptoms may appear 30 to 180 days after exposure and can include a rapid onset of sickness with nausea, vomiting, yellowish skin, fatigue, yellow urine, and abdominal pain. Symptoms during acute infection typically last for a few weeks, though some people may feel sick for up to six months. Deaths resulting from acute stage HBV infections are rare. An HBV infection lasting longer than six months is usually considered chronic. The likelihood of developing chronic hepatitis B is higher for those who are infected with HBV at a younger age. About 90% of those infected during or shortly after birth develop chronic hepatitis B, while less than 10% of those infected after the age of five develop chronic cases. Most of those with chronic disease have no symptoms; however, cirrhosis and liver cancer eventually develop in about 25% of those with chronic HBV.
The virus is transmitted by exposure to infectious blood or body fluids. In areas where the disease is common, infection around the time of birth or from contact with other people's blood during childhood are the most frequent methods by which hepatitis B is acquired. In areas where the disease is rare, intravenous drug use and sexual intercourse are the most frequent routes of infection. Other risk factors include working in healthcare, blood transfusions, dialysis, living with an infected person, travel in countries with high infection rates, and living in an institution. Tattooing and acupuncture led to a significant number of cases in the 1980s; however, this has become less common with improved sterilization. The viruses cannot be spread by holding hands, sharing eating utensils, kissing, hugging, coughing, sneezing, or breastfeeding. The infection can be diagnosed 30 to 60 days after exposure. The diagnosis is usually confirmed by testing the blood for parts of the virus and for antibodies against the virus. It is one of five main hepatitis viruses: A, B, C, D, and E. During an initial infection, care is based on a person's symptoms. In those who develop chronic disease, antiviral medication such as tenofovir or interferon may be useful; however, these drugs are expensive. Liver transplantation is sometimes recommended for cases of cirrhosis or hepatocellular carcinoma.
Hepatitis B infection has been preventable by vaccination since 1982. As of 2022, the hepatitis B vaccine is between 98% and 100% effective in preventing infection. The vaccine is administered in several doses; after an initial dose, two or three more vaccine doses are required at a later time for full effect. The World Health Organization recommends infants receive the vaccine within 24 hours after birth when possible. National programs have made the hepatitis B vaccine available for infants in 190 countries as of the end of 2021. To further prevent infection, the WHO recommends testing all donated blood for hepatitis B before using it for transfusion. Using antiviral prophylaxis to prevent mother-to-child transmission is also recommended, as is following safe sex practices, including the use of condoms. In 2016, the WHO set a goal of eliminating viral hepatitis as a threat to global public health by 2030. Achieving this goal would require the development of therapeutic treatments to cure chronic hepatitis B, as well as preventing its transmission and using vaccines to prevent new infections.
An estimated 296 million people, or 3.8% of the global population, had chronic hepatitis B infections as of 2019. Another 1.5 million developed acute infections that year, and 820,000 deaths occurred as a result of HBV. Cirrhosis and liver cancer are responsible for most HBV-related deaths. The disease is most prevalent in Africa and in the Western Pacific region. Infection rates are 1.5% in Europe and 0.5% in the Americas. According to some estimates, about a third of the world's population has been infected with hepatitis B at one point in their lives. Hepatitis B was originally known as "serum hepatitis".
Signs and symptoms
Acute infection with virus is associated with acute viral hepatitis, an illness that begins with general ill-health, loss of appetite, nausea, vomiting, body aches, mild fever, and dark urine, and then progresses to development of jaundice. The illness lasts for a few weeks and then gradually improves in most affected people. A few people may have a more severe form of liver disease known as fulminant hepatic failure and may die as a result. The infection may be entirely asymptomatic and may go unrecognized.Chronic infection with virus may be asymptomatic or may be associated with chronic inflammation of the liver, leading to cirrhosis over a period of several years. This type of infection dramatically increases the incidence of hepatocellular carcinoma. Across Europe, hepatitis B and C cause approximately 50% of hepatocellular carcinomas. Chronic carriers are encouraged to avoid consuming alcohol as it increases their risk for cirrhosis and liver cancer. virus has been linked to the development of membranous glomerulonephritis.
Symptoms outside of the liver are present in 1–10% of HBV-infected people and include serum-sickness–like syndrome, acute necrotizing vasculitis, membranous glomerulonephritis, and papular acrodermatitis of childhood. The serum-sickness–like syndrome occurs in the setting of acute, often preceding the onset of jaundice. The clinical features are fever, skin rash, and polyarteritis. The symptoms often subside shortly after the onset of jaundice but can persist throughout the duration of acute. About 30–50% of people with acute necrotizing vasculitis are HBV carriers. HBV-associated nephropathy has been described in adults but is more common in children. Membranous glomerulonephritis is the most common form. Other immune-mediated hematological disorders, such as essential mixed cryoglobulinemia and aplastic anemia, have been described as part of the extrahepatic manifestations of HBV infection, but their association is not as well-defined; therefore, they probably should not be considered etiologically linked to HBV.
Cause
Transmission
Transmission of virus results from exposure to infectious blood or body fluids containing blood. HBV is 50 to 100 times more infectious than human immunodeficiency virus. HBV can be transmitted through several routes of infection. In vertical transmission, HBV is passed from mother to child during childbirth. Without intervention, a mother who is positive for HBsAg has a 20% risk of passing the infection to her offspring at the time of birth. This risk is as high as 90% if the mother is also positive for HBeAg.Early life horizontal transmission can occur through bites, lesions, certain sanitary habits, or other contact with secretions. Though HBV is found in virtually every bodily secretion and excretion, only blood, semen, and vaginal secretions have been shown to be infective. Adult horizontal transmission is known to occur through sexual contact, blood transfusions and transfusion with other human blood products, re-use of contaminated needles and syringes. Breastfeeding after proper immunoprophylaxis does not appear to contribute to mother-to-child-transmission of HBV.
Virology
Structure
virus is a member of the hepadnavirus family. The virus particle consists of an outer lipid envelope and an icosahedral nucleocapsid core composed of core protein. These virions are 30–42 nm in diameter. The nucleocapsid encloses the viral DNA and a DNA polymerase that has reverse transcriptase activity. The outer envelope contains embedded proteins that are involved in viral binding of, and entry into, susceptible cells. The virus is one of the smallest enveloped animal viruses. The 42 nm virions, which are capable of infecting liver cells known as hepatocytes, are referred to as "Dane particles". In addition to the Dane particles, filamentous and spherical bodies lacking a core can be found in the serum of infected individuals. These particles are not infectious and are composed of the lipid and protein that forms part of the surface of the virion, which is called the surface antigens, and is produced in excess during the life cycle of the virus.Genome
The genome of HBV is made of circular DNA, but it is unusual because the DNA is not fully double-stranded. One end of the full length strand is linked to the HBV DNA polymerase. The genome is 3020–3320 nucleotides long and 1700–2800 nucleotides long. The negative-sense is complementary to the viral mRNA. The viral DNA is found in the nucleus soon after infection of the cell. The partially double-stranded DNA is rendered fully double-stranded by completion of the sense strand and removal of a protein molecule from the sense strand and a short sequence of RNA from the sense strand. Non-coding bases are removed from the ends of the sense strand and the ends are rejoined. There are four known genes encoded by the genome, called C, X, P, and S. The core protein is coded for by gene C, and its start codon is preceded by an upstream in-frame AUG start codon from which the pre-core protein is produced. HBeAg is produced by proteolytic processing of the pre-core protein. In some rare strains of the virus known as hepatitis B virus precore mutants, no HBeAg is present.The DNA polymerase is encoded by gene P. Gene S is the gene that codes for the surface antigen. The HBsAg gene is one long open reading frame but contains three in frame "start" codons that divide the gene into three sections, pre-S1, pre-S2, and S. Because of the multiple start codons, polypeptides of three different sizes called large, middle, and small are produced. There is a myristyl group, which plays an important role in infection, on the amino-terminal end of the preS1 part of the large protein. In addition to that, N terminus of the L protein have virus attachment and capsid binding sites. Because of that, the N termini of half of the L protein molecules are positioned outside the membrane and the other half positioned inside the membrane.
The function of the protein coded for by gene X is not fully understood but it is associated with the development of liver cancer. It stimulates genes that promote cell growth and inactivates growth regulating molecules.