Hepatitis B overview: Difference between revisions
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==Historical Perspective== | ==Historical Perspective== | ||
The first descriptions of [[hepatitis]] (epidemic [[jaundice]]) are generally attributed to Hippocrates, who identified the disorder during the 5<sup>th</sup> century BCE.<ref name="CDC1">Center for Disease Control and Prevention.Epidemiology and Prevention of Vaccine Preventable Diseases 2012. http://www.cdc.gov/vaccines/pubs/pinkbook/hepa.html</ref> In 1885, the earliest identifiable occurrence of hepatitis B virus was documented by Lurman.<ref name="Hussey1981">{{cite journal|last1=Hussey|first1=Hugh H.|title=The Hepatitis B Saga|journal=JAMA: The Journal of the American Medical Association|volume=245|issue=13|year=1981|pages=1317|issn=0098-7484|doi=10.1001/jama.1981.03310380021018}}</ref> In 1947, the current nomenclature of [[hepatitis A]] (so-called infectious hepatitis) and [[hepatitis B]] (so-called serum hepatitis) was proposed by MacCallum and Bauer. By this time, it was already known that in comparison with hepatitis A, hepatitis B. | |||
Throughout the 20th century, advancements in the recognition, isolation, classification, and prevention of hepatitis B were achieved. Today, the focus around HBV remains on the spread of awareness and prevention across the world, especially in endemic areas that would benefit greatly from immunization programs.<ref name="pmid10194463">{{cite journal| author=Mahoney FJ| title=Update on diagnosis, management, and prevention of hepatitis B virus infection. | journal=Clin Microbiol Rev | year= 1999 | volume= 12 | issue= 2 | pages= 351-66 | pmid=10194463 | doi= | pmc=PMC88921 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10194463 }} </ref><ref name=serum-hepatitis>Neefe, John R., Sydney S. Gellis, and Joseph Stokes. "Homologous serum hepatitis and infectious (epidemic) hepatitis: Studies in volunteers bearing on immunological and other characteristics of the etiological agents." The American journal of medicine 1.1 (1946): 3-22.</ref> | Throughout the 20th century, advancements in the recognition, isolation, classification, and prevention of hepatitis B were achieved. Today, the focus around HBV remains on the spread of awareness and prevention across the world, especially in endemic areas that would benefit greatly from immunization programs.<ref name="pmid10194463">{{cite journal| author=Mahoney FJ| title=Update on diagnosis, management, and prevention of hepatitis B virus infection. | journal=Clin Microbiol Rev | year= 1999 | volume= 12 | issue= 2 | pages= 351-66 | pmid=10194463 | doi= | pmc=PMC88921 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10194463 }} </ref><ref name=serum-hepatitis>Neefe, John R., Sydney S. Gellis, and Joseph Stokes. "Homologous serum hepatitis and infectious (epidemic) hepatitis: Studies in volunteers bearing on immunological and other characteristics of the etiological agents." The American journal of medicine 1.1 (1946): 3-22.</ref> | ||
Revision as of 18:03, 14 October 2016
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Hepatitis B |
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Diagnosis |
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Treatment |
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Case Studies |
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Hepatitis B overview On the Web |
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American Roentgen Ray Society Images of Hepatitis B overview |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Jolanta Marszalek, M.D. [2]; João André Alves Silva, M.D. [3]; Sara Mehrsefat, M.D. [4]
Overview
Chronic Hepatitis B virus (HBV) is a major global health problem, according to the World Health Organization (WHO).[1][2] Hepatitis B virus (HBV) is a double-stranded DNA virus belonging to the family Hepadnaviridae. It is responsible for hepatitis B virus infection in humans, which attacks the liver and causes both acute and chronic disease. During HBV infection, the host's immune response causes both hepatocellular damage and viral clearance. The HBV virion binds to a receptor at the surface of the hepatocyte and enters the cell, where it uses the host's cell mechanisms to replicate its genome and proteins. Transmission occurs from exposure to infectious blood or body fluids. Hepatitis B is often associated with hepatocellular carcinoma. Immune complexes, such as surface antigen-antibody, are important in the pathogenesis of hepatitis B.[3][4] Hepatitis B must be differentiated from other diseases that cause fever, nausea, vomiting, jaundice, hepatomegaly, icteric sclera, elevated ALT, and/or elevated AST, such as other viral hepatitis strains, alcoholic hepatitis, and autoimmune hepatitis.[5] Generally, the highest risk for HBV infection is associated with certain lifestyles, occupations, or environments in which contact with blood from infected persons is frequent. The diagnosis of hepatitis B is made by biochemical assessment of liver function.
In the majority of patients with acute and chronic hepatitis B (HBV), symptoms may initially be non-specific and physical examination will be normal.[6] The diagnosis of hepatitis B is made by biochemical assessment of liver function. Initial laboratory evaluation usually reveals increased bilirubin, ALT, AST, and alkaline phosphatase, as well as decreased protein. Prothrombin time may be prolonged in cases of hepatocellular necrosis. Serologic markers, such as Hepatitis B surface antigen (HBsAg); anti-HBsAg; anti-HBc IgM and anti-HBc IgG; hepatitis Be antigen; and anti-HBeAg confirm the diagnosis of hepatitis B.[2][7]
In the majority of adult patients, the body is able to eliminate the virus without treatment. Currently, there is no treatment available for acute hepatitis B infection. Early antiviral treatment may only be required in fewer than 1% of patients with fulminant hepatitis. Treatment of chronic infection may be necessary to reduce the risk of cirrhosis and liver cancer. Treatment lasts between six months and a year, depending on the medication and genotype. Although none of the available drugs can clear the infection, they can stop the virus from replicating, thus minimizing liver damage. These include the antiviral drugs Lamivudine, Adefovir, Tenofovir, Telbivudine, and Entecavir, as well as immune system modulators such as interferon alpha-2a and pegylated interferon-alpha-2a.[8][9]
Historical Perspective
The first descriptions of hepatitis (epidemic jaundice) are generally attributed to Hippocrates, who identified the disorder during the 5th century BCE.[10] In 1885, the earliest identifiable occurrence of hepatitis B virus was documented by Lurman.[11] In 1947, the current nomenclature of hepatitis A (so-called infectious hepatitis) and hepatitis B (so-called serum hepatitis) was proposed by MacCallum and Bauer. By this time, it was already known that in comparison with hepatitis A, hepatitis B. Throughout the 20th century, advancements in the recognition, isolation, classification, and prevention of hepatitis B were achieved. Today, the focus around HBV remains on the spread of awareness and prevention across the world, especially in endemic areas that would benefit greatly from immunization programs.[12][13]
Pathophysiology
The intracellular hepatitis B virus is a non-cytopathic virus that causes little or no damage to the cell.[1] During HBV infection, the host immune response causes both hepatocellular damage and viral clearance. The HBV virion binds to a receptor at the surface of the hepatocyte and enters the cell, where it uses the host's cell mechanisms to replicate its genome and proteins. Different viral antigens and antibodies are detected in serum throughout the course of the disease, such as: HBsAg, HBcAg, HBeAg, anti-HBs, anti-HBC and anti-HBe. Transmission occurs from exposure to infectious blood or body fluids. Hepatitis B is often associated with hepatocellular carcinoma. Immune complexes, such as surface antigen-antibody, are important in the pathogenesis of hepatitis B.[3][4]
Causes
The hepatitis B virus is responsible for causing hepatitis B. HBV is a double stranded DNA virus belonging to the family Hepadnaviridae. The viral particle consists of an outer lipid envelope and an icosahedral nucleocapsid core composed of protein. The nucleocapsid encloses the viral DNA. HBV DNA polymerase has reverse transcriptase activity. It shows tropism for hepatocytes. Humans are the only natural reservoir.[14] The virus is divided into four major serotypes (adr, adw, ayr, ayw) based on antigenic epitopes presented on its envelope proteins and ten genotypes (A-J) according to overall nucleotide sequence variation of the genome.[15][16]
Differentiating Hepatitis B from other Diseases
Hepatitis B must be differentiated from other diseases that cause fever, nausea, vomiting, jaundice, hepatomegaly, icteric sclera, elevated ALT, AST, such as other viral hepatitis, alcoholic hepatitis, and autoimmune hepatitis.[5][17][18]
Epidemiology and Demographics
Chronic Hepatitis B (HBV) is a major global health problem. According to the World Health Organization (WHO), more than 2 billion people have been infected with HBV. It is a major cause of chronic liver disease worldwide, affecting an estimated 1.25 million persons in the U.S., and more than 240 million people world wide.[1][2]
Risk Factors
Generally, the highest risk for HBV infection is associated with lifestyles, occupations, or environments in which contact with blood from infected persons is frequent. High-risk populations include immigrants/refugees from areas of high HBV endemicity, clients in mental health institutions, injection drug users, and homosexually active men, patients of hemodialysis, and household contacts of HBV carriers. Perinatal transmission from mother to infant at birth is very efficient. If the mother is positive for both HBsAg and HBeAg, 70%–90% of infants will become infected in the absence of postexposure prophylaxis.[19]
Screening
High risk groups should be tested for HBV infection. These include immigrants/refugees from areas of intermediate or high endemicity, persons with chronically elevated aminotransferases, immunocompromised individuals, and persons with a history of injection drug use(IDU).[20] Additionally, screening for hepatocellular carcinoma should extend to any HBV carrier over 40 years with persistent or intermittent ALT elevation and/or high HBV DNA level >2,000 IU/mL.[7]
Natural History, Complications and Prognosis
The course of hepatitis B may be extremely variable. Hepatitis B has different clinical manifestations depending on the patient’s age at infection, immune status, and the stage at which the disease is recognized.[1] During the incubation period patients may experience flu-like symptoms, such as nausea, vomiting, and headaches. A person infected with hepatitis B virus may recover completely, become an asymptomatic carrier of the virus, develop chronic disease, or develop fulminant hepatitis. In acute hepatitis B, the incubation period may range from 45 to 120 days, depending on the amount of virus in the inoculum, host factors, and mode of transmission. These patients may experience the following symptoms: fatigue, nausea, vomiting, anorexia, abdominal discomfort, and jaundice. In most cases, no special diet or treatment are necessary. The risk of developing chronic hepatitis decreases with age, with infants having the highest risk. Chronic hepatitis may progress to: cirrhosis, liver failure, or hepatocellular carcinoma. In most cases the prognosis of acute hepatitis is good, with symptoms lasting 2 to 3 weeks. However, in infants and immunocompromised persons, the risk of developing chronic disease is increased.[1][21]
Diagnosis
Diagnostic criteria
Diagnosis of hepatitis is made by biochemical assessment of liver function. Diagnosis is confirmed by demonstration in sera of specific antigens and/or antibodies. Three clinical useful antigen-antibody systems have been identified for hepatitis B, such as: hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs); antibody (anti-HBc IgM and anti-HBc IgG) to hepatitis B core antigen (HBcAg) and hepatitis B e antigen (HBeAg) and antibody to HBeAg (anti-HBe).[1]
History and symptom
50% of adult patients and the majority of infants and children with acute HBV do not present with symptoms. Symptoms may initially be non-specific.[2] Proper and thorough history taking is important in both acute and chronic HBV infections in order to determine modes of infection transmission as well as to assess risk factors for the progression of HBV-related liver disease.[6][22]
Physical examination
For the majority of patients with acute and chronic hepatitis B (HBV), the physical examination is normal.[6]
Laboratory tests
Diagnosis of hepatitis is made by biochemical assessment of liver function. Initial laboratory evaluation usually reveals: increased bilirubin levels; increased ALT, AST, alkaline phosphatase and decreased protein. Prothrombin time may be prolonged in cases of hepatocellular necrosis and hemoglobin may be low. Initial lymphopenia and neutropenia may be followed by lymphocytosis. Serologic markers, such as Hepatitis B surface antigen (HBsAg); anti-HBsAg; anti-HBc IgM and anti-HBc IgG; hepatitis B e antigen and anti-HBeAg confirm the diagnosis of hepatitis B. These levels fluctuate throughout the course of the disease.[1][2][7]
CT
CT scan may diagnose and/or monitor biliary obstruction, cirrhosis and hepatocellular carcinoma, in hepatitis B patients.:[24]
MRI
The MRI may be used to diagnose/monitor biliary obstruction, cirrhosis, and hepatocellular carcinoma in hepatitis B patients. MRI findings in these patients may include nodular appearance and signs of portal hypertension, such as ascites and splenomegaly.[24]
Ultrasound
The ultrasound may be used as a screening tool in patients with chronic hepatitis for the early detection of hepatic cirrhosis. HBsAg carriers with cirrhosis should be echographically evaluated every 6 months.
Treatment
Medical therapy
The majority of adults are able to eliminate the virus without treatment. Currently, there is no treatment available for acute hepatitis B infection. Symptomatic treatment may be indicated. Early antiviral treatment may only be required in fewer than 1% of patients, whose hepatitis B takes a very aggressive course, such as in cases of fulminant hepatitis. Treatment of chronic infection may be necessary to reduce the risk of cirrhosis and liver cancer. Chronically infected patients with persistently elevated serum alanine aminotransferase and HBV DNA levels are candidates for therapy. Treatment lasts from six months to a year, depending on the medication and genotype. Although none of the available drugs can clear the infection, they can stop the virus from replicating, thus minimizing liver damage. These include antiviral drugs Lamivudine, Adefovir, Tenofovir, Telbivudine and Entecavir, and immune system modulators, such as interferon alpha-2a and pegylated interferon-alpha-2a.[8][9][25][26]
Surgery
The treatment of hepatitis B usually involves no surgical procedures. However, among patients with advanced liver damage secondary to HBV infection or liver failure in fulminant hepatitis, liver transplantation may be beneficial.
Primary Prevention
The risk of transmission of hepatitis B may be diminished by following certain measures proposed by the WHO. These include: vaccination of all infants within 24 hours of birth; vaccination of certain risk groups, such as travelers to endemic areas and healthcare workers (if these have not been vaccinated yet); avoidance of sexual contact with a person who has acute or chronic hepatitis B; and avoiding to share personal items, such as razors or toothbrushes. HBV vaccine is effective in preventing HBV infections when it is given either before exposure or shortly after exposure.[1][27][28]
Vaccination
Hepatitis B vaccine is the most effective tool in preventing the transmission of HBV and HDV. Vaccines are composed of the surface antigen of HBV (HBsAg), and are produced by two different methods include plasma derived and recombinant DNA. The primary hepatitis B immunization series conventionally consists of three doses of vaccine. Vaccination of infants and, in particular, delivery of hepatitis B vaccine within 24 hours of birth is 90–95% effective in preventing infection with HBV as well as decreasing HBV transmission if followed by at least two other doses. WHO recommends universal hepatitis B vaccination for all infants, and that the first dose should be given as soon as possible after birth.[1][29]This strategy has resulted in a dramatic decrease in the prevalence of CHB among young children in regions of the world where universal infant vaccination programs have been implemented. A proportion of vaccinated children (5–10%) have a poor response to vaccination, and will remain susceptible as adults to acquisition of HBV infection.[1][30]
Vertical transmission
Hepatitis B virus (HBV) infection in a pregnant woman poses a serious risk to her infant at birth. Without postexposure immunoprophylaxis, approximately 40% of infants born to HBV-infected mothers in the United States will develop chronic HBV infection, approximately one-fourth of whom will eventually die from chronic liver disease.[31]
Secondary Prevention
Hepatitis B Immunoglobulin (HBIG) is a form of passive immunization when given shortly before, or soon after exposure to hepatitis B virus. It is also administered in combination with HBV vaccines to newborns of HBsAg positive mothers.[1][28]
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 World Health Organization, Guidelines for the Prevention, Care, and Treatment of persons with chronic Hepatitis B Infection. (March 2015). http://apps.who.int/iris/bitstream/10665/154590/1/9789241549059_eng.pdf Accessed on October 4th, 2016
- ↑ 2.0 2.1 2.2 2.3 2.4 Center for Disease Control and Prevention. Guidelines for Hepatitis Sureveillance and Case Management 2009.http://www.cdc.gov/hepatitis/Statistics/SurveillanceGuidelines.htm
- ↑ 3.0 3.1 Zhang YY, Hu KQ (2015). "Rethinking the pathogenesis of hepatitis B virus (HBV) infection". J Med Virol. 87 (12): 1989–99. doi:10.1002/jmv.24270. PMID 25989114.
- ↑ 4.0 4.1 Chang KM, Liu M (2016). "Chronic hepatitis B: immune pathogenesis and emerging immunotherapeutics". Curr Opin Pharmacol. 30: 93–105. doi:10.1016/j.coph.2016.07.013. PMID 27570126.
- ↑ 5.0 5.1 Centers for Disease Control and Prevention. Viral Hepatitis http://www.cdc.gov/hepatitis/ Accessed on October 4th, 2016
- ↑ 6.0 6.1 6.2 Rotman Y, Brown TA, Hoofnagle JH (2009). "Evaluation of the patient with hepatitis B." Hepatology. 49 (5 Suppl): S22–7. doi:10.1002/hep.22976. PMC 2881483. PMID 19399815.
- ↑ 7.0 7.1 7.2 AASLD guidelines for treatment of chronic hepatitis B. Hepatology (2016)http://onlinelibrary.wiley.com/doi/10.1002/hep.28156/full Accessed on October 10th, 2016
- ↑ 8.0 8.1 Vargas HE, Dodson FS, Rakela J (2002). "A concise update on the status of liver transplantation for hepatitis B virus: the challenges in 2002". Liver Transpl. 8 (1): 2–9. doi:10.1053/jlts.2002.29765. PMID 11799479.
- ↑ 9.0 9.1 Omata M (1990). "Significance of extrahepatic replication of hepatitis B virus". Hepatology. 12 (2): 364–6. PMID 2202639.
- ↑ Center for Disease Control and Prevention.Epidemiology and Prevention of Vaccine Preventable Diseases 2012. http://www.cdc.gov/vaccines/pubs/pinkbook/hepa.html
- ↑ Hussey, Hugh H. (1981). "The Hepatitis B Saga". JAMA: The Journal of the American Medical Association. 245 (13): 1317. doi:10.1001/jama.1981.03310380021018. ISSN 0098-7484.
- ↑ Mahoney FJ (1999). "Update on diagnosis, management, and prevention of hepatitis B virus infection". Clin Microbiol Rev. 12 (2): 351–66. PMC 88921. PMID 10194463.
- ↑ Neefe, John R., Sydney S. Gellis, and Joseph Stokes. "Homologous serum hepatitis and infectious (epidemic) hepatitis: Studies in volunteers bearing on immunological and other characteristics of the etiological agents." The American journal of medicine 1.1 (1946): 3-22.
- ↑ 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.
- ↑ Magnius LO, Norder H (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.
|access-date=requires|url=(help) - ↑ Lin CL, Kao JH (2011). "The clinical implications of hepatitis B virus genotype: Recent advances". J Gastroenterol Hepatol. 26 Suppl 1: 123–30. doi:10.1111/j.1440-1746.2010.06541.x. PMID 21199523.
- ↑ Cohen JA, Kaplan MM (1979). "The SGOT/SGPT ratio--an indicator of alcoholic liver disease". Dig Dis Sci. 24 (11): 835–8. PMID 520102.
- ↑ Williams AL, Hoofnagle JH (1988). "Ratio of serum aspartate to alanine aminotransferase in chronic hepatitis. Relationship to cirrhosis". Gastroenterology. 95 (3): 734–9. PMID 3135226.
- ↑ Center for Disease Control and Prevention. Epidemiology and Prevention of Vaccine-Preventable Diseases. Hepatitis B 2012.http://www.cdc.gov/vaccines/pubs/pinkbook/hepb.html
- ↑ U.S Preventive Services Task Force. Hepatitis B. (2016) https://www.uspreventiveservicestaskforce.org/BrowseRec/Search?s=hepatitis+b Accessed on October 10th, 2016
- ↑ Mandell, Gerald (2005). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. New York: Elsevier/Churchill Livingstone. ISBN 0443066434.
- ↑ Lok AS, McMahon BJ (2009). "Chronic hepatitis B: update 2009". Hepatology. 50 (3): 661–2. doi:10.1002/hep.23190. PMID 19714720.
- ↑ "http://www.who.int/en/". External link in
|title=(help) - ↑ 24.0 24.1 Bialecki ES, Di Bisceglie AM (2005). "Diagnosis of hepatocellular carcinoma". HPB (Oxford). 7 (1): 26–34. doi:10.1080/13651820410024049. PMC 2023919. PMID 18333158.
- ↑ McGory RW, Ishitani MB, Oliveira WM, Stevenson WC, McCullough CS, Dickson RC; et al. (1996). "Improved outcome of orthotopic liver transplantation for chronic hepatitis B cirrhosis with aggressive passive immunization". Transplantation. 61 (9): 1358–64. PMID 8629297.
- ↑ Marzano A, Gaia S, Ghisetti V, Carenzi S, Premoli A, Debernardi-Venon W; et al. (2005). "Viral load at the time of liver transplantation and risk of hepatitis B virus recurrence". Liver Transpl. 11 (4): 402–9. doi:10.1002/lt.20402. PMID 15776431.
- ↑ Morbidity and Mortality Weekly Report. A Comprehensive Immunization Strategy to Eliminate Transmission of Hepatitis B Virus Infection in the United States. (2006). http://www.cdc.gov/mmwr/PDF/rr/rr5516.pdf Accessed on October 4th, 2016
- ↑ 28.0 28.1 Centers for Disease Control and Prevention. Prevention and Control of Infections with Hepatitis Viruses in Correctional Settings http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5201a1.htm Accessed on October 4th 2016
- ↑ Ni JD, Xiong YZ, Wang XJ, Xiu LC. Does increased hepatitis B vaccination dose lead to a better immune response in HIV- infected patients than standard dose vaccination: a meta-analysis? Int J STD AIDS. 2013;24(2):117–22.
- ↑ Liu CJ, Liou JM, Chen DS, Chen P J.Natural course and treatment of dual hepatitis B virus and hepatitis C virus infections. J Formos Med Assoc Taiwan. 2005;104(11):783–91.
- ↑ Centers for Disease Control and Prevention. Viral Hepatitis - Hepatitis B Information. Perinatal Transmission (2016) http://www.cdc.gov/hepatitis/hbv/perinatalxmtn.htm Accessed on October 5th, 2016