Hepatitis B overview: Difference between revisions
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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 [[Hepatitis B surface antigen|surface antigen]]-[[antibody]], are important in the [[pathogenesis]] of hepatitis B.<ref name="pmid25989114">{{cite journal| author=Zhang YY, Hu KQ| title=Rethinking the pathogenesis of hepatitis B virus (HBV) infection. | journal=J Med Virol | year= 2015 | volume= 87 | issue= 12 | pages= 1989-99 | pmid=25989114 | doi=10.1002/jmv.24270 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25989114 }} </ref><ref name="pmid27570126">{{cite journal| author=Chang KM, Liu M| title=Chronic hepatitis B: immune pathogenesis and emerging immunotherapeutics. | journal=Curr Opin Pharmacol | year= 2016 | volume= 30 | issue= | pages= 93-105 | pmid=27570126 | doi=10.1016/j.coph.2016.07.013 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27570126 }} </ref> | 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 [[Hepatitis B surface antigen|surface antigen]]-[[antibody]], are important in the [[pathogenesis]] of hepatitis B.<ref name="pmid25989114">{{cite journal| author=Zhang YY, Hu KQ| title=Rethinking the pathogenesis of hepatitis B virus (HBV) infection. | journal=J Med Virol | year= 2015 | volume= 87 | issue= 12 | pages= 1989-99 | pmid=25989114 | doi=10.1002/jmv.24270 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25989114 }} </ref><ref name="pmid27570126">{{cite journal| author=Chang KM, Liu M| title=Chronic hepatitis B: immune pathogenesis and emerging immunotherapeutics. | journal=Curr Opin Pharmacol | year= 2016 | volume= 30 | issue= | pages= 93-105 | pmid=27570126 | doi=10.1016/j.coph.2016.07.013 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27570126 }} </ref> | ||
[[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]].<ref name=CDC-Viral-Hepatitis>Centers for Disease Control and Prevention. Viral Hepatitis http://www.cdc.gov/hepatitis/ Accessed on October 4th, 2016</ref> | [[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]].<ref name=CDC-Viral-Hepatitis>Centers for Disease Control and Prevention. Viral Hepatitis http://www.cdc.gov/hepatitis/ Accessed on October 4th, 2016</ref> | ||
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. | 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. | The diagnosis of [[hepatitis B]] is made by [[biochemical]] assessment of [[liver]] function. | ||
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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 [[HBsAg|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.<ref name="CDC1">Center for Disease Control and Prevention. Hepatitis B Epidemiology and Prevention of Vaccine-Preventable Diseases 2012.http://www.cdc.gov/vaccines/pubs/pinkbook/hepb.html</ref><ref name=Hepatology> 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</ref> | 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 [[HBsAg|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.<ref name="CDC1">Center for Disease Control and Prevention. Hepatitis B Epidemiology and Prevention of Vaccine-Preventable Diseases 2012.http://www.cdc.gov/vaccines/pubs/pinkbook/hepb.html</ref><ref name=Hepatology> 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</ref> | ||
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|interferon alpha-2a]] and [[pegylated interferon-alpha-2a]].<ref name="pmid11799479">{{cite journal| author=Vargas HE, Dodson FS, Rakela J| title=A concise update on the status of liver transplantation for hepatitis B virus: the challenges in 2002. | journal=Liver Transpl | year= 2002 | volume= 8 | issue= 1 | pages= 2-9 | pmid=11799479 | doi=10.1053/jlts.2002.29765 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11799479 }} </ref><ref name="pmid2202639">{{cite journal| author=Omata M| title=Significance of extrahepatic replication of hepatitis B virus. | journal=Hepatology | year= 1990 | volume= 12 | issue= 2 | pages= 364-6 | pmid=2202639 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2202639 }} </ref> | 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 drug|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|interferon alpha-2a]] and [[pegylated interferon-alpha-2a]].<ref name="pmid11799479">{{cite journal| author=Vargas HE, Dodson FS, Rakela J| title=A concise update on the status of liver transplantation for hepatitis B virus: the challenges in 2002. | journal=Liver Transpl | year= 2002 | volume= 8 | issue= 1 | pages= 2-9 | pmid=11799479 | doi=10.1053/jlts.2002.29765 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11799479 }} </ref><ref name="pmid2202639">{{cite journal| author=Omata M| title=Significance of extrahepatic replication of hepatitis B virus. | journal=Hepatology | year= 1990 | volume= 12 | issue= 2 | pages= 364-6 | pmid=2202639 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2202639 }} </ref> | ||
==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/ | 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. Hepatitis B Epidemiology and Prevention of Vaccine-Preventable Diseases 2012.http://www.cdc.gov/vaccines/pubs/pinkbook/hepb.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. | ||
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> | ||
==Pathophysiology== | ==Pathophysiology== | ||
The intracellular [[hepatitis B virus]] is a non-cytopathic virus that causes little or no damage to the cell.<ref name=WHO-Guideline-Hepatitis-B> 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</ref> 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 cell's mechanisms to replicate its own [[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.<ref name="pmid25989114">{{cite journal| author=Zhang YY, Hu KQ| title=Rethinking the pathogenesis of hepatitis B virus (HBV) infection. | journal=J Med Virol | year= 2015 | volume= 87 | issue= 12 | pages= 1989-99 | pmid=25989114 | doi=10.1002/jmv.24270 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25989114 }} </ref><ref name="pmid27570126">{{cite journal| author=Chang KM, Liu M| title=Chronic hepatitis B: immune pathogenesis and emerging immunotherapeutics. | journal=Curr Opin Pharmacol | year= 2016 | volume= 30 | issue= | pages= 93-105 | pmid=27570126 | doi=10.1016/j.coph.2016.07.013 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27570126 }} </ref> | The intracellular [[hepatitis B virus]] is a non-cytopathic virus that causes little or no damage to the cell.<ref name=WHO-Guideline-Hepatitis-B> 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</ref> 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 cell's mechanisms to replicate its own [[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.<ref name="pmid25989114">{{cite journal| author=Zhang YY, Hu KQ| title=Rethinking the pathogenesis of hepatitis B virus (HBV) infection. | journal=J Med Virol | year= 2015 | volume= 87 | issue= 12 | pages= 1989-99 | pmid=25989114 | doi=10.1002/jmv.24270 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25989114 }} </ref><ref name="pmid27570126">{{cite journal| author=Chang KM, Liu M| title=Chronic hepatitis B: immune pathogenesis and emerging immunotherapeutics. | journal=Curr Opin Pharmacol | year= 2016 | volume= 30 | issue= | pages= 93-105 | pmid=27570126 | doi=10.1016/j.coph.2016.07.013 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27570126 }} </ref> | ||
==Causes== | ==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.<ref name=Baron>{{Cite book |author=Zuckerman AJ |chapter=Hepatitis Viruses |title=Baron's Medical Microbiology |editor=Baron S, ''et al'' |edition=4th |publisher=University of Texas Medical Branch |year=1996|url=http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed.section.3738|isbn=0-9631172-1-1 }}</ref> | 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 of the virus.<ref name=Baron>{{Cite book |author=Zuckerman AJ |chapter=Hepatitis Viruses |title=Baron's Medical Microbiology |editor=Baron S, ''et al'' |edition=4th |publisher=University of Texas Medical Branch |year=1996|url=http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed.section.3738|isbn=0-9631172-1-1 }}</ref> | ||
HBV is divided into four major [[serotype|serotypes]] (adr, adw, ayr, ayw) based on antigenic [[epitope|epitopes]] presented on its envelope [[proteins]] and ten [[genotype|genotypes]] (A-J) according to overall [[nucleotide]] sequence variation of the [[genome]].<ref name="pmid8666521">{{cite journal |author=Magnius LO, Norder H |title=Subtypes, genotypes and molecular epidemiology of the hepatitis B virus as reflected by sequence variability of the S-gene |journal=[[Intervirology]] |volume=38 |issue=1-2 |pages=24–34 |year=1995 |pmid=8666521 |doi= |url= |accessdate=2012-02-08}}</ref><ref name="pmid21199523">{{cite journal| author=Lin CL, Kao JH| title=The clinical implications of hepatitis B virus genotype: Recent advances. | journal=J Gastroenterol Hepatol | year= 2011 | volume= 26 Suppl 1 | issue= | pages= 123-30 | pmid=21199523 | doi=10.1111/j.1440-1746.2010.06541.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21199523 }} </ref> | |||
==Differentiating Hepatitis B from other Diseases== | ==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]] | [[Hepatitis B]] must be differentiated from other diseases that cause [[fever]], [[nausea]], [[vomiting]], [[jaundice]], [[hepatomegaly]], icteric [[sclera]], and/or elevated [[ALT]] and [[AST]], such as other forms of [[viral hepatitis]], [[alcoholic hepatitis]], and [[autoimmune hepatitis]].<ref name=CDC-Viral-Hepatitis>Centers for Disease Control and Prevention. Viral Hepatitis http://www.cdc.gov/hepatitis/ Accessed on October 4th, 2016</ref><ref name="pmid520102">{{cite journal| author=Cohen JA, Kaplan MM| title=The SGOT/SGPT ratio--an indicator of alcoholic liver disease. | journal=Dig Dis Sci | year= 1979 | volume= 24 | issue= 11 | pages= 835-8 | pmid=520102 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=520102 }} </ref><ref name="pmid3135226">{{cite journal| author=Williams AL, Hoofnagle JH| title=Ratio of serum aspartate to alanine aminotransferase in chronic hepatitis. Relationship to cirrhosis. | journal=Gastroenterology | year= 1988 | volume= 95 | issue= 3 | pages= 734-9 | pmid=3135226 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3135226 }} </ref> | ||
==Epidemiology and Demographics== | ==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 | 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 people in the United States, and more than 240 million people worldwide.<ref name=WHO-Guideline-Hepatitis-B> 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</ref><ref name="CDC">Center for Disease Control and Prevention. Guidelines for Hepatitis Sureveillance and Case Management 2009.http://www.cdc.gov/hepatitis/Statistics/SurveillanceGuidelines.htm</ref> | ||
==Risk Factors== | ==Risk Factors== | ||
Generally, the highest risk for HBV infection is associated with lifestyles, occupations, or environments in which contact with blood from infected | Generally, the highest risk for HBV infection is associated with lifestyles, occupations, or environments in which contact with [[blood]] from infected patients is frequent. High-risk populations include immigrants/refugees from areas of high HBV endemicity, clients in mental health institutions, [[injecting drug users]], men who have sex with men (MSM), patients receiving [[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 post-exposure [[prophylaxis]].<ref name="Pnkbk">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</ref> | ||
==Screening== | ==Screening== | ||
High risk groups should be tested for [[HBV]] infection. These include immigrants/refugees from areas of intermediate or high [[endemic|endemicity]], | High-risk groups should be tested for [[HBV]] infection. These include immigrants/refugees from areas of intermediate or high [[endemic|endemicity]], patients with chronically elevated [[aminotransferases]], [[immunocompromised]] individuals, and people with a history of injection drug use ([[intravenous drug use (recreational)|IDU]]).<ref name=USPTF-HepatitsB>U.S Preventive Services Task Force. Hepatitis B. (2016) https://www.uspreventiveservicestaskforce.org/BrowseRec/Search?s=hepatitis+b Accessed on October 10th, 2016</ref> | ||
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]] | Additionally, screening for [[hepatocellular carcinoma]] should extend to any [[HBV]] carrier over 40 years of age with persistent or intermittent [[ALT]] elevation and/or high [[HBV]] [[DNA]] levels (>2,000 IU/mL).<ref name=Hepatology> 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</ref> | ||
==Natural History, Complications and Prognosis== | ==Natural History, Complications and Prognosis== | ||
The course of hepatitis B | The course of hepatitis B is 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.<ref name=WHO-Guideline-Hepatitis-B> 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</ref> 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 [[acute liver failure|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 the mode of [[transmission]]. These patients may experience the following symptoms: [[fatigue]], [[nausea]], [[vomiting]], [[anorexia]], [[abdominal pain]], 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]] patients, the risk of developing chronic disease is increased.<ref name=WHO-Guideline-Hepatitis-B> 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</ref><ref>{{cite book | last = Mandell | first = Gerald | title = Mandell, Douglas, and Bennett's principles and practice of infectious diseases | publisher = Elsevier/Churchill Livingstone | location = New York | year = 2005 | isbn = 0443066434 }}</ref> | ||
==Diagnosis== | ==Diagnosis== | ||
===Diagnostic criteria=== | ===Diagnostic criteria=== | ||
The diagnosis of [[hepatitis]] is made by [[biochemical]] assessment of [[liver]] function. A [[diagnosis]] is confirmed by the presence of specific [[antigens]] and/or [[antibodies]] in [[serum|sera]]. Three clinically useful antigen-antibody systems have been identified for hepatitis B. These include 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).<ref name=WHO-Guideline-Hepatitis-B> 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</ref> | |||
[[Image:HBV serum markers.png|center|thumb|500px|Hepatitis B viral antigens and antibodies detectable in the blood following acute infection]] | [[Image:HBV serum markers.png|center|thumb|500px|Hepatitis B viral antigens and antibodies detectable in the blood following acute infection - CC BY 3.0, https://en.wikipedia.org/w/index.php?curid=14144661]] | ||
===History and symptom=== | ===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.<ref name="CDC1">Center for Disease Control and Prevention. Hepatitis B Epidemiology and Prevention of Vaccine-Preventable Diseases 2012.http://www.cdc.gov/vaccines/pubs/pinkbook/hepb.html</ref> | 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.<ref name="CDC1">Center for Disease Control and Prevention. Hepatitis B Epidemiology and Prevention of Vaccine-Preventable Diseases 2012.http://www.cdc.gov/vaccines/pubs/pinkbook/hepb.html</ref> It is critical to obtain an accurate and thorough history in cases of 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]].<ref name="pmid19399815">{{cite journal| author=Rotman Y, Brown TA, Hoofnagle JH| title=Evaluation of the patient with hepatitis B. | journal=Hepatology | year= 2009 | volume= 49 | issue= 5 Suppl | pages= S22-7 | pmid=19399815 | doi=10.1002/hep.22976 | pmc=PMC2881483 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19399815 }} </ref><ref name="pmid19714720">{{cite journal| author=Lok AS, McMahon BJ| title=Chronic hepatitis B: update 2009. | journal=Hepatology | year= 2009 | volume= 50 | issue= 3 | pages= 661-2 | pmid=19714720 | doi=10.1002/hep.23190 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19714720 }} </ref> | ||
===Physical examination=== | ===Physical examination=== | ||
For the majority of patients with acute and chronic [[hepatitis B]] ([[HBV]]), the physical examination is normal.<ref name="pmid19399815">{{cite journal| author=Rotman Y, Brown TA, Hoofnagle JH| title=Evaluation of the patient with hepatitis B. | journal=Hepatology | year= 2009 | volume= 49 | issue= 5 Suppl | pages= S22-7 | pmid=19399815 | doi=10.1002/hep.22976 | pmc=PMC2881483 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19399815 }} </ref> | For the majority of patients with acute and chronic [[hepatitis B]] ([[HBV]]), the physical examination is normal.<ref name="pmid19399815">{{cite journal| author=Rotman Y, Brown TA, Hoofnagle JH| title=Evaluation of the patient with hepatitis B. | journal=Hepatology | year= 2009 | volume= 49 | issue= 5 Suppl | pages= S22-7 | pmid=19399815 | doi=10.1002/hep.22976 | pmc=PMC2881483 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19399815 }} </ref> | ||
===Laboratory tests=== | ===Laboratory tests=== | ||
The diagnosis of [[hepatitis]] is made by the biochemical assessment of [[liver function]]. An initial laboratory evaluation usually reveals increased [[bilirubin]] levels; increased [[ALT]], [[AST]], and [[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 [[HBsAg|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.<ref name=WHO-Guideline-Hepatitis-B> 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</ref><ref name="CDC1">Center for Disease Control and Prevention. Hepatitis B Epidemiology and Prevention of Vaccine-Preventable Diseases 2012.http://www.cdc.gov/vaccines/pubs/pinkbook/hepb.html</ref><ref name=Hepatology> 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</ref> | |||
[[image:HepB Assay Results.jpg|thumb|center|800px|Hepatitis B assay results <SMALL> Adapted from ''[http://www.who.int/en/ World Health Organization]''<ref>{{Cite web | title = WHO | url = http://www.who.int/en/}}</ref></SMALL>]] | [[image:HepB Assay Results.jpg|thumb|center|800px|Hepatitis B assay results <SMALL> Adapted from ''[http://www.who.int/en/ World Health Organization]''<ref>{{Cite web | title = WHO | url = http://www.who.int/en/}}</ref></SMALL>]] | ||
===CT=== | ===CT=== | ||
[[CT | [[CT scans]] may diagnose and/or monitor [[biliary]] obstruction, [[cirrhosis]], and [[hepatocellular carcinoma]] in hepatitis B patients.:<ref name="pmid18333158">{{cite journal| author=Bialecki ES, Di Bisceglie AM| title=Diagnosis of hepatocellular carcinoma. | journal=HPB (Oxford) | year= 2005 | volume= 7 | issue= 1 | pages= 26-34 | pmid=18333158 | doi=10.1080/13651820410024049 | pmc=PMC2023919 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18333158 }} </ref> | ||
===MRI=== | ===MRI=== | ||
An [[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]].<ref name="pmid18333158">{{cite journal| author=Bialecki ES, Di Bisceglie AM| title=Diagnosis of hepatocellular carcinoma. | journal=HPB (Oxford) | year= 2005 | volume= 7 | issue= 1 | pages= 26-34 | pmid=18333158 | doi=10.1080/13651820410024049 | pmc=PMC2023919 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18333158 }} </ref> | |||
===Ultrasound=== | ===Ultrasound=== | ||
[[Ultrasounds]] 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 [[ultrasound|echographically]] evaluated every 6 months. | |||
==Treatment== | ==Treatment== | ||
===Medical therapy=== | ===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 [[alanine transaminase|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]] | 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 therapy|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 [[alanine transaminase|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 (e.g., [[Lamivudine]], [[Adefovir]], [[Tenofovir]], [[Telbivudine]] and [[Entecavir]]) and [[immune system]] modulators, including [[Interferon|interferon alpha-2a]] and [[pegylated interferon-alpha-2a]].<ref name="pmid11799479">{{cite journal| author=Vargas HE, Dodson FS, Rakela J| title=A concise update on the status of liver transplantation for hepatitis B virus: the challenges in 2002. | journal=Liver Transpl | year= 2002 | volume= 8 | issue= 1 | pages= 2-9 | pmid=11799479 | doi=10.1053/jlts.2002.29765 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11799479 }} </ref><ref name="pmid2202639">{{cite journal| author=Omata M| title=Significance of extrahepatic replication of hepatitis B virus. | journal=Hepatology | year= 1990 | volume= 12 | issue= 2 | pages= 364-6 | pmid=2202639 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2202639 }} </ref><ref name="pmid8629297">{{cite journal| author=McGory RW, Ishitani MB, Oliveira WM, Stevenson WC, McCullough CS, Dickson RC et al.| title=Improved outcome of orthotopic liver transplantation for chronic hepatitis B cirrhosis with aggressive passive immunization. | journal=Transplantation | year= 1996 | volume= 61 | issue= 9 | pages= 1358-64 | pmid=8629297 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8629297 }} </ref><ref name="pmid15776431">{{cite journal| author=Marzano A, Gaia S, Ghisetti V, Carenzi S, Premoli A, Debernardi-Venon W et al.| title=Viral load at the time of liver transplantation and risk of hepatitis B virus recurrence. | journal=Liver Transpl | year= 2005 | volume= 11 | issue= 4 | pages= 402-9 | pmid=15776431 | doi=10.1002/lt.20402 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15776431 }} </ref> | ||
===Surgery=== | ===Surgery=== | ||
Surgery is usually not indicated for the treatment of hepatitis B. However, for patients with advanced [[liver damage secondary]] to HBV infection or [[liver failure]] in fulminant hepatitis, [[liver transplantation]] may be beneficial. | |||
===Primary Prevention=== | ===Primary Prevention=== | ||
The risk of [[transmission]] of hepatitis B may be diminished by following | The risk of [[transmission]] of hepatitis B may be diminished by following measures proposed by the [[WHO]]. These include [[vaccination]] of all infants within 24 hours of birth; [[vaccination]] of members of certain risk groups, such as travelers to [[endemic]] areas and healthcare workers (if they have not been vaccinated yet); avoidance of sexual contact with a person who has acute or [[chronic hepatitis B]]; and avoiding sharing personal items such as razors or toothbrushes. The [[HBV]] vaccine is effective in preventing [[HBV infection|HBV infections]] when it is administered either before or shortly after exposure.<ref name=WHO-Guideline-Hepatitis-B> 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</ref><ref name=MMWR-Hepatitis-B>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 </ref><ref name=MMWR-Hepatitis> 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</ref> | ||
====Vaccination==== | ====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]]) | The [[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, including 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.<ref name=WHO-Guideline-Hepatitis-B> 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</ref><ref Name=Hepatitis-B-Vac>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.</ref>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.<ref name=WHO-Guideline-Hepatitis-B> 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</ref><ref name=hepatitis-B-virus>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.</ref> | 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 further advises that the first dose should be given as soon as possible after birth.<ref name=WHO-Guideline-Hepatitis-B> 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</ref><ref Name=Hepatitis-B-Vac>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.</ref> 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 small proportion of vaccinated children (5–10%) have a poor response to [[vaccination]], and will remain susceptible as adults to acquisition of HBV infection.<ref name=WHO-Guideline-Hepatitis-B> 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</ref><ref name=hepatitis-B-virus>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.</ref> | ||
====Vertical transmission==== | ====Vertical transmission==== | ||
Hepatitis B virus (HBV) infection in a pregnant woman poses a serious risk to the fetus. 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]].<ref name=CDC-Perinatal-Transmission> 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</ref> | Hepatitis B virus ([[HBV]]) infection in a pregnant woman poses a serious risk to the fetus. 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]].<ref name=CDC-Perinatal-Transmission> 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</ref> | ||
===Secondary Prevention=== | ===Secondary Prevention=== | ||
Hepatitis B Immunoglobulin (HBIG) is a form of passive [[immunization]] when given shortly before | 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.<ref name=WHO-Guideline-Hepatitis-B> 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</ref><ref name=MMWR-Hepatitis> 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</ref> | ||
==References == | ==References == | ||
{{Reflist|2}} | {{Reflist|2}} | ||
{{WH}} | {{WH}} | ||
{{WS}} | {{WS}} | ||
[[Category:Gastroenterology]] | |||
[[Category:FinalQCRequired]] | |||
[[Category:Emergency mdicine]] | |||
[[Category:Disease]] | |||
[[Category:Up-To-Date]] | |||
[[Category:Infectious disease]] | |||
[[Category:Hepatology]] | |||
Latest revision as of 22:05, 29 July 2020
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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.[7][8]
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.[9][10]
Historical Perspective
The first descriptions of hepatitis (epidemic jaundice) are generally attributed to Hippocrates, who identified the disorder during the 5th century BCE.[7] 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. 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 cell's mechanisms to replicate its own 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 of the virus.[14] HBV 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, and/or elevated ALT and AST, such as other forms of 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 people in the United States, and more than 240 million people worldwide.[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 patients is frequent. High-risk populations include immigrants/refugees from areas of high HBV endemicity, clients in mental health institutions, injecting drug users, men who have sex with men (MSM), patients receiving 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 post-exposure prophylaxis.[19]
Screening
High-risk groups should be tested for HBV infection. These include immigrants/refugees from areas of intermediate or high endemicity, patients with chronically elevated aminotransferases, immunocompromised individuals, and people with a history of injection drug use (IDU).[20] Additionally, screening for hepatocellular carcinoma should extend to any HBV carrier over 40 years of age with persistent or intermittent ALT elevation and/or high HBV DNA levels (>2,000 IU/mL).[8]
Natural History, Complications and Prognosis
The course of hepatitis B is 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 the mode of transmission. These patients may experience the following symptoms: fatigue, nausea, vomiting, anorexia, abdominal pain, 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 patients, the risk of developing chronic disease is increased.[1][21]
Diagnosis
Diagnostic criteria
The diagnosis of hepatitis is made by biochemical assessment of liver function. A diagnosis is confirmed by the presence of specific antigens and/or antibodies in sera. Three clinically useful antigen-antibody systems have been identified for hepatitis B. These include 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.[7] It is critical to obtain an accurate and thorough history in cases of 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
The diagnosis of hepatitis is made by the biochemical assessment of liver function. An initial laboratory evaluation usually reveals increased bilirubin levels; increased ALT, AST, and 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][7][8]
CT
CT scans may diagnose and/or monitor biliary obstruction, cirrhosis, and hepatocellular carcinoma in hepatitis B patients.:[24]
MRI
An 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
Ultrasounds 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 (e.g., Lamivudine, Adefovir, Tenofovir, Telbivudine and Entecavir) and immune system modulators, including interferon alpha-2a and pegylated interferon-alpha-2a.[9][10][25][26]
Surgery
Surgery is usually not indicated for the treatment of hepatitis B. However, for 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 measures proposed by the WHO. These include vaccination of all infants within 24 hours of birth; vaccination of members of certain risk groups, such as travelers to endemic areas and healthcare workers (if they have not been vaccinated yet); avoidance of sexual contact with a person who has acute or chronic hepatitis B; and avoiding sharing personal items such as razors or toothbrushes. The HBV vaccine is effective in preventing HBV infections when it is administered either before or shortly after exposure.[1][27][28]
Vaccination
The 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, including 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 further advises 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 small 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 the fetus. 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 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 7.3 Center for Disease Control and Prevention. Hepatitis B Epidemiology and Prevention of Vaccine-Preventable Diseases 2012.http://www.cdc.gov/vaccines/pubs/pinkbook/hepb.html
- ↑ 8.0 8.1 8.2 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
- ↑ 9.0 9.1 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.
- ↑ 10.0 10.1 Omata M (1990). "Significance of extrahepatic replication of hepatitis B virus". Hepatology. 12 (2): 364–6. PMID 2202639.
- ↑ 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.
- ↑ "WHO".
- ↑ 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