Hepatitis B 

hepatitis B virus (HBV) which affects the liver. It was originally known as "serum hepatitis". Many people have no symptoms during the initial infection. Some develop a rapid onset of sickness with vomiting, yellow skin, dark urine and abdominal pain. Often these symptoms last a few weeks and rarely result in death. It may take 30 to 180 days for symptoms to begin. Less than 10% of those infected develop chronic hepatitis B. In those with chronic disease cirrhosis and liver cancer may eventually develop.      

 

 

 The hepatitis B virus reproduces in liver cells, but the virus itself is not the direct cause of damage to the liver. Rather, the presence of the virus triggers an immune response from the body as the body tries to eliminate the virus and recover from the infection. This immune response causes inflammation and may seriously injure liver calls. Therefore, there is a balance between the protective and destructive effects of the immune response to the hepatitis B virus. 

 

The infection has been preventable by vaccination since 1982. During the initial infection, care is based on the symptoms present. In those who develop chronic disease antiviral medication such as tenofovir or interferon maybe useful, however these drugs are expensive.
About a third of the world population has been infected at one point in their lives, including 350 million who are chronic carriers. Over 750,000 people die of hepatitis B each year. The disease has caused outbreaks in parts of Asia and Africa, and it is now only common in China and sub-Saharan Africa. Between 5 and 10% of adults in sub-Saharan Africa and East Asia have chronic disease. Research is in progress to create edible HBV vaccines in foods such as potatoes, carrots, and bananas. The disease may affect other apes aswell.

 

History

The earliest record of an epidemic caused by hepatitis B virus was made by Lurman in 1885. An outbreak of smallpox occurred in Bremen in 1883 and 1,289 shipyard employees were vaccinated with lymph from other people. After several weeks, and up to eight months later, 191 of the vaccinated workers became ill with jaundice and were diagnosed as suffering from serum hepatitis. Other employees who had been inoculated with different batches of lymph remained healthy. Lurman's paper, now regarded as a classical example of an epidemiological study, proved that contaminated lymph was the source of the outbreak. Later, numerous similar outbreaks were reported following the introduction, in 1909, of hypodermic needles that were used, and, more importantly, reused, for administering Salvarsan for the treatment of syphilis. The virus was not discovered until 1966 when Baruch Blumberg, then working at the National Institutes of Health (NIH), discovered the Australia antigen (later known to be hepatitis B surface antigen, or HBsAg) in the blood of Australian aboriginal people. Although a virus had been suspected since the research published by MacCallum in 1947, D.S. Dane and others discovered the virus particle in 1970 by electron microscopy. By the early 1980s the genome of the virus had been sequenced, and the first vaccines were being tested.

In 2004, an estimated 350 million individuals were infected worldwide. National and regional prevalence ranges from over 10% in Asia to under 0.5% in the United States and northern Europe.
Routes of infection include vertical transmission (such as through childbirth), early life horizontal transmission (bites, lesions, and sanitary habits), and adult horizontal transmission (sexual contact, intravenous drug use).
The primary method of transmission reflects the prevalence of chronic HBV infection in a given area. In low prevalence areas such as the continental United States and Western Europe, injection drug abuse and unprotected sex are the primary methods, although other factors may also be important. In moderate prevalence areas, which include Eastern Europe, Russia, and Japan, where 2–7% of the population is chronically infected, the disease is predominantly spread among children. In high-prevalence areas such as China and South East Asia, transmission during childbirth is most common, although in other areas of high endemicity such as Africa, transmission during childhood is a significant factor. The prevalence of chronic HBV infection in areas of high endemicity is at least 8% with 10-15% prevalence in Africa/Far East. As of 2010, China has 120 million infected people, followed by India and Indonesia with 40 million and 12 million, respectively. According to World Health Organization (WHO), an estimated 600,000 people die every year related to the infection.
In the United States about 19,000 new cases occurred in 2011 down nearly 90% from 1990.

 in 2004, an estimated 350 million individuals were infected worldwide. National and regional prevalence ranges from over 10% in Asia to under 0.5% in the United States and northern Europe.
Routes of infection include vertical transmission (such as through childbirth), early life horizontal transmission (bites, lesions, and sanitary habits), and adult horizontal transmission (sexual contact, intravenous drug use).
The primary method of transmission reflects the prevalence of chronic HBV infection in a given area. In low prevalence areas such as the continental United States and Western Europe, injection drug abuse and unprotected sex are the primary methods, although other factors may also be important. In moderate prevalence areas, which include Eastern Europe, Russia, and Japan, where 2–7% of the population is chronically infected, the disease is predominantly spread among children. In high-prevalence areas such as China and South East Asia, transmission during childbirth is most common, although in other areas of high endemicity such as Africa, transmission during childhood is a significant factor. The prevalence of chronic HBV infection in areas of high endemicity is at least 8% with 10-15% prevalence in Africa/Far East. As of 2010, China has 120 million infected people, followed by India and Indonesia with 40 million and 12 million, respectively. According to World Health Organization (WHO), an estimated 600,000 people die every year related to the infection.
In the United States about 19,000 new cases occurred in 2011 down nearly 90% from 1990.






 

Transmission

The virus is transmitted by exposure to infectious blood or body fluids. Infection around the time of birth is the most frequent way hepatitis B is acquired in areas of the world where the disease is common. In areas where the disease is rare intravenous drug use and sex are the most frequent routes of infection. Other risk factors include working in a healthcare setting, blood transfusions, dialysis, sharing razors or toothbrushes with an infected person, travel in countries where the infection rate is high, 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 sterility. The hepatitis B viruses cannot be spread by holding hands, sharing eating utensils or drinking glasses, kissing, hugging, coughing, sneezing, or breastfeeding. It is 50 to 100 times more infectious than HIV.

 

Signs and symptoms

The symptoms of Hepatitis B include the following:

• Tendency of mild fever
• Increasing tiredness
• Joint pains
• Aching limbs symptoms
• Loosing of the appetite
• Sickness filling
• Vomiting tendency
• Alcohol intolerance etc.

Moreover it may also be developed as jaundice, a disease which is quite be able to make your skin as well as eyes yellow.  Though this happen in your due to the color substance inside our blood or billirubin.

Structure Hepatitis B virus (HBV)

 is a member of the hepadnavirus family. The virus particle (virion) consists of an outer lipid envelope and an icosahedral nucleocapsid core composed of 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, and the 42 nM virions, which are capable of infecting 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 (HBsAg), and is produced in excess during the life cycle of the virus.

 B virus primarily interferes with the functions of the liver by replicating in liver cells, known as hepatocytes. A functional receptor is NTCP.There is evidence that the receptor in the closely related duck hepatitis B virus is carboxypeptidase D. The virions bind to the host cell via the preS domain of the viral surface antigen and are subsequently internalized by endocytosis. HBV-preS-specific receptors are expressed primarily on hepatocytes; however, viral DNA and proteins have also been detected in extrahepatic sites, suggesting that cellular receptors for HBV may also exist on extrahepatic cells.

During HBV infection, the host immune response causes both hepatocellular damage and viral clearance. Although the innate immune response does not play a significant role in these processes, the adaptive immune response, in particular virus-specific cytotoxic T lymphocytes(CTLs), contributes to most of the liver injury associated with HBV infection. CTLs eliminate HBV infection by killing infected cells and producing antiviral cytokines, which are then used to purge HBV from viable hepatocytes. Although liver damage is initiated and mediated by the CTLs, antigen-nonspecific inflammatory cells can worsen CTL-induced immunopathology, and platelets activated at the site of infection may facilitate the accumulation of CTLs in the liver.

   

Diagnosis

Infection with hepatitis B is suspected when the medical history and the physical examination reveal risk factors for the infection or symptoms and signs that are suggestive of hepatitis B. Abnormalities in the liver tests (blood tests) also can raise suspicion; however, abnormal liver tests can result from many conditions that affect the liver. The diagnosis of hepatitis B can be made only with specific hepatitis B virus blood tests. These tests are known as hepatitis 'markers' or 'serology.'
Markers found in the blood can confirm hepatitis B infection and differentiate acute from chronic infection. These markers are substances produced by the hepatitis B virus (antigens) and antibodies produced by the immune system to fight the virus. Hepatitis B virus has three antigens for which there are commonly-used tests - the surface antigen (HBsAg), the core antigen (HBcAg) and the e antigen (HBeAg).

HBsAg and anti-HBs

The presence of hepatitis B surface antigen (HBsAg) in the blood indicates that the patient is currently infected with the virus. HBsAg appears an average of four weeks after initial exposure to the virus. Individuals who recover from acute hepatitis B infections clear the blood of HBsAg within approximately four months after the onset of symptoms. These individuals develop antibodies to HBsAg (anti-HBs). Anti-HBs provides complete immunity to subsequent hepatitis B viral infection. Similarly, individuals who are successfully vaccinated against hepatitis B produce anti-HBs in the blood.
Patients who fail to clear the virus during an acute episode develop chronic hepatitis B. The diagnosis of chronic hepatitis B is made when the HBsAg is present in the blood for at least six months. In chronic hepatitis B, HBsAg can be detected for many years, and anti-HBs does not appear.

Anti-HBc

In acute hepatitis, a specific class of early antibodies (IgM) appears that is directed against the hepatitis B core antigen (anti-HBc IgM). Later, another class of antibody, anti-HBc IgG, develops and persists for life, regardless of whether the individual recovers or develops chronic infection. Only anti-HBc IgM can be used to diagnose an acute hepatitis B infection.

 

HBeAg, anti-HBe, and pre-core mutations

Hepatitis B e antigen (HBeAg) is present when the hepatitis B virus is actively multiplying, whereas the production of the antibody, anti-HBe, (also called HBeAg seroconversion) signifies a more inactive state of the virus and a lower risk of transmission.
In some individuals infected with hepatitis B virus, the genetic material for the virus has undergone a structural change, called a pre-core mutation. This mutation results in an inability of the hepatitis B virus to produce HBeAg, even though the virus is actively reproducing. This means that even though no HBeAg is detected in the blood of people with the mutation, the hepatitis B virus is still active in these people and they can infect others.

Hepatitis B virus DNA

The best marker of hepatitis B virus reproduction is the level of hepatitis B virus DNA in the blood. Detection of hepatitis B virus DNA in a blood sample signals that the virus is actively multiplying. In acute hepatitis, HBV DNA is present soon after infection, but is eliminated over time in patients' who clear the infection. In chronic hepatitis, levels of HBV DNA often continue to be elevated for many years and then decrease as the immune system controls the virus. HBV DNA levels are sometimes referred to as the 'viral load'.

How are the hepatitis B blood tests interpreted?

The following table gives the usual interpretation for sets of results from hepatitis B blood (serological) tests.

Most Likely Status*	Tests	Results
Susceptible, not infected, not immune	HBsAg anti-HBc anti-HBs	negative negative negative
Immune due to natural infection	HBsAg anti-HBc anti-HBs	negative positive positive
Immune do to hepatitis B vaccination	HBsAg anti-HBc anti-HBS	negative negative positive
Acutely infected	HBsAg anti-HBc IgM anti-HBc anti-HBs	positive positive positive negative
Chronically infected	HBsAg anti-HBc IgM anti-HBc anti-HBs	positive positive negative negative

*Interpretation of the hepatitis B virus blood tests should always be made by an experienced clinician with knowledge of the patient's medical history, physical examination, and results of the standard liver blood tests.

Hepatitis B vaccine

Vaccines for the prevention of hepatitis B have been routinely recommended for infants since 1991 in the United States. Most vaccines are given in three doses over a course of months. A protective response to the vaccine is defined as an anti-HBs antibody concentration of at least 10 mIU/ml in the recipient's serum. The vaccine is more effective in children and 95 percent of those vaccinated have protective levels of antibody. This drops to around 90% at 40 years of age and to around 75 percent in those over 60 years. The protection afforded by vaccination is long lasting even after antibody levels fall below 10 mIU/ml. Vaccination at birth is recommended for all infants of HBV infected mothers. A combination of hepatitis B immune globulin and an accelerated course of HBV vaccine prevents perinatal HBV transmission in around 90% of cases.
All those with a risk of exposure to body fluids such as blood should be vaccinated, if not already. Testing to verify effective immunization is recommended and further doses of vaccine are given to those who are not sufficiently immunized.
In assisted reproductive technology, sperm washing is not necessary for males with hepatitis B to prevent transmission, unless the female partner has not been effectively vaccinated. In females with hepatitis B, the risk of transmission from mother to child with IVF is no different from the risk in spontaneous conception.
Those at high risk of infection should be tested as there is effective treatment for those who have the disease. Groups that screening is recommended for include those who have not been vaccinated and one of the following: people from areas of the world where hepatitis B occurs in more than 2%, those with HIV, intravenous drug users, men who have sex with men, and those who live with someone with hepatitis B.

 

Treatment

Acute hepatitis B infection does not usually require treatment and most adults clear the infection spontaneously. Early antiviral treatment may be required in fewer than 1% of people, whose infection takes a very aggressive course (fulminant hepatitis) or who are immunocompromised. On the other hand, treatment of chronic infection may be necessary to reduce the risk of cirrhosis and liver cancer. Chronically infected individuals with persistently elevated serum alanine aminotransferase, a marker of liver damage, and HBV DNA levels are candidates for therapy. Treatment lasts from six months to a year, depending on medication and genotype.
Although none of the available drugs can clear the infection, they can stop the virus from replicating, thus minimizing liver damage. As of 2008, there are seven medications licensed for treatment of hepatitis B infection in the United States. These include antiviral drugs lamivudine (Epivir), adefovir (Hepsera), tenofovir (Viread), telbivudine (Tyzeka) and entecavir (Baraclude), and the two immune system modulators interferon alpha-2a and PEGylated interferon alpha-2a (Pegasys). The use of interferon, which requires injections daily or thrice weekly, has been supplanted by long-acting PEGylated interferon, which is injected only once weekly. However, some individuals are much more likely to respond than others, and this might be because of the genotype of the infecting virus or the person's heredity. The treatment reduces viral replication in the liver, thereby reducing the viral load (the amount of virus particles as measured in the blood). Response to treatment differs between the genotypes. Interferon treatment may produce an e antigen seroconversion rate of 37% in genotype A but only a 6% seroconversion in type D. Genotype B has similar seroconversion rates to type A while type C seroconverts only in 15% of cases. Sustained e antigen loss after treatment is ~45% in types A and B but only 25–30% in types C and D.

Society and culture

World Hepatitis Day, observed July 28, aims to raise global awareness of hepatitis B and hepatitis C and encourage prevention, diagnosis and treatment. It has been led by the World Hepatitis Alliance since 2007 and in May 2010, it got global endorsement from the World Health Organization.

References

1. Chang MH (June 2007). "Hepatitis B virus infection". Semin Fetal Neonatal Med 12 (3): 160–167. doi:10.1016/j.siny.2007.01.013. PMID 17336170.
2. Sleisenger, MH; Feldman M; Friedman LS (2006). Fordtran's gastrointestinal and liver disease: pathophysiology, diagnosis, management (8th ed.). Philadelphia: Saunders.
3. "Hepatitis B FAQs for the Public — Transmission". U.S. Centers for Disease Control and Prevention (CDC). Retrieved 2011-11-29.
4. Viral Hepatitis (4th ed. ed.). Hoboken: Wiley. 2013. p. 83. ISBN 9781118637302. |first1= missing |last1= in Authors list (help)
5. "Hepatitis B". National Institute of Health. Retrieved 2010-11-23.
6. "Understanding Hepatitis -- the Basics". WebMD.
7. Pungpapong S, Kim WR, Poterucha JJ (2007). "Natural History of Hepatitis B Virus Infection: an Update for Clinicians". Mayo Clinic Proceedings 82 (8): 967–975. doi:10.4065/82.8.967. PMID 17673066.
8. Schilsky ML (2013). "Hepatitis B "360"". Transplantation Proceedings 45 (3): 982–985. doi:10.1016/j.transproceed.2013.02.099. PMID 23622604.
9. Williams R (2006). "Global challenges in liver disease". Hepatology (Baltimore, Md.) 44 (3): 521–526. doi:10.1002/hep.21347. PMID 16941687.
10. Terrault N, Roche B, Samuel D; Roche; Samuel (July 2005). "Management of the hepatitis B virus in the liver transplantation setting: a European and an American perspective". Liver Transpl. 11 (7): 716–32. doi:10.1002/lt.20492. PMID 15973718.
11. El-Serag HB, Rudolph KL; Rudolph (June 2007). "Hepatocellular carcinoma: epidemiology and molecular carcinogenesis". Gastroenterology 132 (7): 2557–76. doi:10.1053/j.gastro.2007.04.061. PMID 17570226.
12. El-Serag HB (22 September 2011). "Hepatocellular carcinoma". New England Journal of Medicine 365 (12): 1118–27. doi:10.1056/NEJMra1001683. PMID 21992124.
13. Gan SI, Devlin SM, Scott-Douglas NW, Burak KW; Devlin; Scott-Douglas; Burak (October 2005). "Lamivudine for the treatment of membranous glomerulopathy secondary to chronic hepatitis B infection". Canadian journal of gastroenterology = Journal canadien de gastroenterologie 19 (10): 625–9. PMID 16247526.
14. Dienstag JL (February 1981). "Hepatitis B as an immune complex disease". Seminars in Liver Disease 1 (1): 45–57. doi:10.1055/s-2008-1063929. PMID 6126007
15. Trepo C, Guillevin L; Guillevin (May 2001). "Polyarteritis nodosa and extrahepatic manifestations of HBV infection: the case against autoimmune intervention in pathogenesis". Journal of Autoimmunity 16 (3): 269–74. doi:10.1006/jaut.2000.0502. PMID 11334492.
16. Alpert E, Isselbacher KJ, Schur PH; Isselbacher; Schur (July 1971). "The pathogenesis of arthritis associated with viral hepatitis. Complement-component studies". The New England Journal of Medicine 285 (4): 185–9. doi:10.1056/NEJM197107222850401. PMID 4996611.
17. Liang TJ (May 2009). "Hepatitis B: the virus and disease". Hepatology (Baltimore, Md.) 49 (5 Suppl): S13–21. doi:10.1002/hep.22881. PMC 2809016. PMID 19399811.
18. Gocke DJ, Hsu K, Morgan C, Bombardieri S, Lockshin M, Christian CL; Hsu; Morgan; Bombardieri; Lockshin; Christian (December 1970). "Association between polyarteritis and Australia antigen". Lancet 2 (7684): 1149–53. doi:10.1016/S0140-6736(70)90339-9. PMID 4098431.
19. Lai KN, Li PK, Lui SF, Au TC, Tam JS, Tong KL, Lai FM; Li; Lui; Au; Tam; Tong; Lai (May 1991). "Membranous nephropathy related to hepatitis B virus in adults". The New England Journal of Medicine 324 (21): 1457–63. doi:10.1056/NEJM199105233242103. PMID 2023605.
20. Takekoshi Y, Tanaka M, Shida N, Satake Y, Saheki Y, Matsumoto S; Tanaka; Shida; Satake; Saheki; Matsumoto (November 1978). "Strong association between membranous nephropathy and hepatitis-B surface antigenaemia in Japanese children". Lancet 2 (8099): 1065–8. doi:10.1016/S0140-6736(78)91801-9. PMID 82085.
21. Zuckerman AJ (1996). "Hepatitis Viruses". In Baron S, et al. Baron's Medical Microbiology (4th ed.). University of Texas Medical Branch. ISBN 0-9631172-1-1.
22. Locarnini S (2004). "Molecular Virology of Hepatitis B Virus". Seminars in Liver Disease 24: 3–10. doi:10.1055/s-2004-828672. PMID 15192795.
23. Harrison T (2009). Desk Encyclopedia of General Virology. Boston: Academic Press. p. 455. ISBN 0-12-375146-2.
24. Howard CR (1986). "The Biology of Hepadnaviruses". Journal of General Virology 67 (7): 1215–1235. doi:10.1099/0022-1317-67-7-1215. PMID 3014045.
25. Kay A, Zoulim F; Zoulim (2007). "Hepatitis B virus genetic variability and evolution". Virus research 127 (2): 164–176. doi:10.1016/j.virusres.2007.02.021. PMID 17383765.
26. Beck J, Nassal M; Nassal (January 2007). "Hepatitis B virus replication". World J. Gastroenterol. 13 (1): 48–64. doi:10.3748/wjg.v13.i1.48. PMC 4065876. PMID 17206754.
27. Li W, Miao X, Qi Z, Zeng W, Liang J, Liang Z; Miao; Qi; Zeng; Liang; Liang (2010). "Hepatitis B virus X protein upregulates HSP90alpha expression via activation of c-Myc in human hepatocarcinoma cell line, HepG2". Virol. J. 7: 45. doi:10.1186/1743-422X-7-45. PMC 2841080. PMID 20170530.
28. Yan H, Zhong G, Xu G, He W, Jing Z, Gao Z, Huang Y, Qi Y, Peng B, Wang H, Fu L, Song M, Chen P, Gao W, Ren B, Sun Y, Cai T, Feng X, Sui J, Li W; Zhong; Xu; He; Jing; Gao; Huang; Qi; Peng; Wang; Fu; Song; Chen; Gao; Ren; Sun; Cai; Feng; Sui; Li (2012). "Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus". ELife 1: e00049. doi:10.7554/eLife.00049. PMC 3485615. PMID 23150796.
29. Bruss V (January 2007). "Hepatitis B virus morphogenesis". World J. Gastroenterol. 13 (1): 65–73. PMC 4065877. PMID 17206755.
30. Kramvis A, Kew M, François G; Kew; François (March 2005). "Hepatitis B virus genotypes". Vaccine 23 (19): 2409–23. doi:10.1016/j.vaccine.2004.10.045. PMID 15752827.
31. Magnius LO, Norder H; Norder (1995). "Subtypes, genotypes and molecular epidemiology of the hepatitis B virus as reflected by sequence variability of the S-gene". Intervirology 38 (1–2): 24–34. PMID 8666521.