Hepatitis E laboratory tests: Difference between revisions
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__NOTOC__ | __NOTOC__ | ||
{{Hepatitis E}} | {{Hepatitis E}} | ||
{{CMG}}; {{AE | {{CMG}}; {{AE}} {{JS}} | ||
==Overview== | ==Overview== | ||
Hepatitis E cannot be distinguished from other types of [[hepatitis]] based on clinical manifestations alone. Although blood markers of liver injury, such as elevated [[aminotransferases]] may be identified, definitive diagnosis of hepatitis E is done by [[serologic]] tests. [[Viral load]] and [[antibody]] titers will vary according to the stage of the [[infection]]: during the [[incubation period]], the [[HEV|virus]] may be detected in blood and in stool; during the clinical manifestation of the disease, [[ALT]] and [[AST]] are often elevated, the [[HEV|virus]] may be detected in stool, and anti-HEV [[IgM]] and anti-HEV [[IgG]] may be detected; during the recovery phase, [[IgM]] levels decrease, being detected during 3 to 12 months, while [[IgG]] levels may remain detectable throughout many years. [[Amplification]] techniques are also useful for detecting [[HEV infection]], viral [[genotyping]], and identifying specific [[genomic]] sequences. | |||
==Laboratory Findings== | ==Laboratory Findings== | ||
Every patient with acute or chronic hepatitis | Every patient with acute or chronic hepatitis that cannot be explained by other causes, should be tested for hepatitis E.<ref name="pmid22537448">{{cite journal| author=Wedemeyer H, Pischke S, Manns MP| title=Pathogenesis and treatment of hepatitis e virus infection. | journal=Gastroenterology | year= 2012 | volume= 142 | issue= 6 | pages= 1388-1397.e1 | pmid=22537448 | doi=10.1053/j.gastro.2012.02.014 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22537448 }} </ref> Hepatitis E may be diagnosed by detecting either the [[HEV]] [[nucleic acids]], or the [[antibodies]] against the [[HEV|virus]]. Due to the short permanence of the [[HEV|virus]] in blood and feces, and to the ease of the technique, [[serologic]] studies are usually preferred. Unfortunately, the available assays show different [[specificity]] and [[sensitivity]], and are only available at certain centers.<ref name="pmid23013075">{{cite journal| author=Hoofnagle JH, Nelson KE, Purcell RH| title=Hepatitis E. | journal=N Engl J Med | year= 2012 | volume= 367 | issue= 13 | pages= 1237-44 | pmid=23013075 | doi=10.1056/NEJMra1204512 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23013075 }} </ref><ref name="pmid22549046">{{cite journal| author=Kamar N, Bendall R, Legrand-Abravanel F, Xia NS, Ijaz S, Izopet J et al.| title=Hepatitis E. | journal=Lancet | year= 2012 | volume= 379 | issue= 9835 | pages= 2477-88 | pmid=22549046 | doi=10.1016/S0140-6736(11)61849-7 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22549046 }} </ref> Acute hepatitis E is diagnosed by the detection of anti-HEV [[IgM]] against viral [[antigens]], often by [[enzyme immunoassay]].<ref name="pmid19321696">{{cite journal| author=Legrand-Abravanel F, Thevenet I, Mansuy JM, Saune K, Vischi F, Peron JM et al.| title=Good performance of immunoglobulin M assays in diagnosing genotype 3 hepatitis E virus infections. | journal=Clin Vaccine Immunol | year= 2009 | volume= 16 | issue= 5 | pages= 772-4 | pmid=19321696 | doi=10.1128/CVI.00438-08 | pmc=PMC2681577 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19321696 }} </ref> | ||
Throughout the course of infection, serologic markers will vary according to the stage of the disease:<ref name="pmid23013075">{{cite journal| author=Hoofnagle JH, Nelson KE, Purcell RH| title=Hepatitis E. | journal=N Engl J Med | year= 2012 | volume= 367 | issue= 13 | pages= 1237-44 | pmid=23013075 | doi=10.1056/NEJMra1204512 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23013075 }} </ref> | Throughout the course of [[infection]], [[serologic]] markers will vary according to the stage of the disease:<ref name="pmid23013075">{{cite journal| author=Hoofnagle JH, Nelson KE, Purcell RH| title=Hepatitis E. | journal=N Engl J Med | year= 2012 | volume= 367 | issue= 13 | pages= 1237-44 | pmid=23013075 | doi=10.1056/NEJMra1204512 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23013075 }} </ref><ref name="pmid22549046">{{cite journal| author=Kamar N, Bendall R, Legrand-Abravanel F, Xia NS, Ijaz S, Izopet J et al.| title=Hepatitis E. | journal=Lancet | year= 2012 | volume= 379 | issue= 9835 | pages= 2477-88 | pmid=22549046 | doi=10.1016/S0140-6736(11)61849-7 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22549046 }} </ref><ref name="pmid22537448">{{cite journal| author=Wedemeyer H, Pischke S, Manns MP| title=Pathogenesis and treatment of hepatitis e virus infection. | journal=Gastroenterology | year= 2012 | volume= 142 | issue= 6 | pages= 1388-1397.e1 | pmid=22537448 | doi=10.1053/j.gastro.2012.02.014 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22537448 }} </ref> | ||
{| style="border: 2px solid #DCDCDC; font-size: 90%; width: 30%;" | |||
|+ '''Laboratory findings''' | |||
|- | |||
! style="width: 75px; background: #4479BA; text-align: center;"|{{fontcolor|#FFF|Stage of Infection}} | |||
! style="width: 200px; background: #4479BA; text-align: center;"| {{fontcolor|#FFF|Findings}} | |||
|- | |||
| style="background: #F5F5F5; padding: 5px; text-align: center;"| '''Incubation period''' | |||
| style="background: #DCDCDC; padding: 5px;"| | |||
*Rise of [[viremia]] | |||
*Detection of [[HEV]] in stool | |||
|- | |||
| style="background: #F5F5F5; padding: 5px; text-align: center;"| '''Symptom onset''' | |||
| style="background: #DCDCDC; padding: 5px;"| | |||
*[[IgM]] and [[IgG]] antibody detection | |||
*Elevations on serum [[aminotransferase]]s ([[ALT]], [[AST]]) and [[symptom]] onset | |||
*[[HEV]] detected in stool | |||
|- | |||
| style="background: #F5F5F5; padding: 5px; text-align: center;"| '''Recovery''' | |||
| style="background: #DCDCDC; padding: 5px;"| | |||
*[[Viral]] clearance | |||
*Increase of [[IgG]] titers (detectable for years to life) | |||
*Decrease of [[IgM]] levels (detectable for 3 to 12 months) | |||
*[[HEV]] detected in stool during the initial period of recovery | |||
|- | |||
|} | |||
The | The detection of increased levels of anti-HEV [[IgG]] may indicate recent [[HEV]] infection.<ref name="pmid22537448">{{cite journal| author=Wedemeyer H, Pischke S, Manns MP| title=Pathogenesis and treatment of hepatitis e virus infection. | journal=Gastroenterology | year= 2012 | volume= 142 | issue= 6 | pages= 1388-1397.e1 | pmid=22537448 | doi=10.1053/j.gastro.2012.02.014 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22537448 }} </ref> | ||
Several assays are based on the [[HEV]] [[genotype]], therefore, even though the [[specificity]] may be high, [[sensitivity]] of different tests for the remaining [[genotype]]s may be lower.<ref name="pmid22537448">{{cite journal| author=Wedemeyer H, Pischke S, Manns MP| title=Pathogenesis and treatment of hepatitis e virus infection. | journal=Gastroenterology | year= 2012 | volume= 142 | issue= 6 | pages= 1388-1397.e1 | pmid=22537448 | doi=10.1053/j.gastro.2012.02.014 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22537448 }} </ref> | |||
[[Immunocompromised]] patients may have a delayed [[immune response]] to [[HEV]], hence delayed [[seroconversion]]. For that reason, these patients should be tested for HEV RNA.<ref name="pmid19866448">{{cite journal| author=Pischke S, Suneetha PV, Baechlein C, Barg-Hock H, Heim A, Kamar N et al.| title=Hepatitis E virus infection as a cause of graft hepatitis in liver transplant recipients. | journal=Liver Transpl | year= 2010 | volume= 16 | issue= 1 | pages= 74-82 | pmid=19866448 | doi=10.1002/lt.21958 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19866448 }} </ref> The [[RNA]] of the virus may be detected in blood and stool for several weeks, and if quantified, it may be a marker to evaluate the response to treatment.<ref name="pmid22537448">{{cite journal| author=Wedemeyer H, Pischke S, Manns MP| title=Pathogenesis and treatment of hepatitis e virus infection. | journal=Gastroenterology | year= 2012 | volume= 142 | issue= 6 | pages= 1388-1397.e1 | pmid=22537448 | doi=10.1053/j.gastro.2012.02.014 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22537448 }} </ref><ref name="pmid21307208">{{cite journal| author=Baylis SA, Hanschmann KM, Blümel J, Nübling CM, HEV Collaborative Study Group| title=Standardization of hepatitis E virus (HEV) nucleic acid amplification technique-based assays: an initial study to evaluate a panel of HEV strains and investigate laboratory performance. | journal=J Clin Microbiol | year= 2011 | volume= 49 | issue= 4 | pages= 1234-9 | pmid=21307208 | doi=10.1128/JCM.02578-10 | pmc=PMC3122834 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21307208 }} </ref> | |||
Hepatitis E | ===Enzyme Immunoassays=== | ||
Enzyme [[immunoassays]] are directed to the [[ORF]]2 and [[ORF]]3 proteins. These tests have low [[sensitivity]] and [[specificity]], requiring further improvements.<ref name="pmid21932388">{{cite journal| author=Aggarwal R, Jameel S| title=Hepatitis E. | journal=Hepatology | year= 2011 | volume= 54 | issue= 6 | pages= 2218-26 | pmid=21932388 | doi=10.1002/hep.24674 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21932388 }} </ref> | |||
===RT-PCR=== | |||
[[Amplification]] techniques are used for the identification of [[HEV]] [[nucleic acids]]. These techniques also allow:<ref name="pmid21932388">{{cite journal| author=Aggarwal R, Jameel S| title=Hepatitis E. | journal=Hepatology | year= 2011 | volume= 54 | issue= 6 | pages= 2218-26 | pmid=21932388 | doi=10.1002/hep.24674 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21932388 }} </ref> | |||
*Detection of [[HEV infection]] | |||
*[[Genotyping]] of [[HEV]] | |||
*Identification of specific [[genomic]] sequences | |||
[[Amplification]] techniques may have low [[sensitivity]] because when performed, [[viral load]] in blood and feces may be low or unidentifiable.<ref name="pmid21932388">{{cite journal| author=Aggarwal R, Jameel S| title=Hepatitis E. | journal=Hepatology | year= 2011 | volume= 54 | issue= 6 | pages= 2218-26 | pmid=21932388 | doi=10.1002/hep.24674 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21932388 }} </ref> | |||
==References== | ==References== | ||
{{reflist|2}} | {{reflist|2}} | ||
{{WS}} | |||
{{WH}} | |||
[[Category:Hepatitis|E]] | [[Category:Hepatitis|E]] | ||
[[Category:Viruses]] | [[Category:Viruses]] | ||
[[Category:Gastroenterology]] | |||
[[Category:Emergency mdicine]] | |||
[[Category:Disease]] | |||
[[Category:Up-To-Date]] | |||
[[Category:Infectious disease]] | [[Category:Infectious disease]] | ||
[[Category: | [[Category:Hepatology]] | ||
Latest revision as of 22:07, 29 July 2020
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]
Overview
Hepatitis E cannot be distinguished from other types of hepatitis based on clinical manifestations alone. Although blood markers of liver injury, such as elevated aminotransferases may be identified, definitive diagnosis of hepatitis E is done by serologic tests. Viral load and antibody titers will vary according to the stage of the infection: during the incubation period, the virus may be detected in blood and in stool; during the clinical manifestation of the disease, ALT and AST are often elevated, the virus may be detected in stool, and anti-HEV IgM and anti-HEV IgG may be detected; during the recovery phase, IgM levels decrease, being detected during 3 to 12 months, while IgG levels may remain detectable throughout many years. Amplification techniques are also useful for detecting HEV infection, viral genotyping, and identifying specific genomic sequences.
Laboratory Findings
Every patient with acute or chronic hepatitis that cannot be explained by other causes, should be tested for hepatitis E.[1] Hepatitis E may be diagnosed by detecting either the HEV nucleic acids, or the antibodies against the virus. Due to the short permanence of the virus in blood and feces, and to the ease of the technique, serologic studies are usually preferred. Unfortunately, the available assays show different specificity and sensitivity, and are only available at certain centers.[2][3] Acute hepatitis E is diagnosed by the detection of anti-HEV IgM against viral antigens, often by enzyme immunoassay.[4]
Throughout the course of infection, serologic markers will vary according to the stage of the disease:[2][3][1]
| Stage of Infection | Findings |
|---|---|
| Incubation period | |
| Symptom onset | |
| Recovery |
The detection of increased levels of anti-HEV IgG may indicate recent HEV infection.[1] Several assays are based on the HEV genotype, therefore, even though the specificity may be high, sensitivity of different tests for the remaining genotypes may be lower.[1]
Immunocompromised patients may have a delayed immune response to HEV, hence delayed seroconversion. For that reason, these patients should be tested for HEV RNA.[5] The RNA of the virus may be detected in blood and stool for several weeks, and if quantified, it may be a marker to evaluate the response to treatment.[1][6]
Enzyme Immunoassays
Enzyme immunoassays are directed to the ORF2 and ORF3 proteins. These tests have low sensitivity and specificity, requiring further improvements.[7]
RT-PCR
Amplification techniques are used for the identification of HEV nucleic acids. These techniques also allow:[7]
- Detection of HEV infection
- Genotyping of HEV
- Identification of specific genomic sequences
Amplification techniques may have low sensitivity because when performed, viral load in blood and feces may be low or unidentifiable.[7]
References
- ↑ 1.0 1.1 1.2 1.3 1.4 Wedemeyer H, Pischke S, Manns MP (2012). "Pathogenesis and treatment of hepatitis e virus infection". Gastroenterology. 142 (6): 1388–1397.e1. doi:10.1053/j.gastro.2012.02.014. PMID 22537448.
- ↑ 2.0 2.1 Hoofnagle JH, Nelson KE, Purcell RH (2012). "Hepatitis E." N Engl J Med. 367 (13): 1237–44. doi:10.1056/NEJMra1204512. PMID 23013075.
- ↑ 3.0 3.1 Kamar N, Bendall R, Legrand-Abravanel F, Xia NS, Ijaz S, Izopet J; et al. (2012). "Hepatitis E." Lancet. 379 (9835): 2477–88. doi:10.1016/S0140-6736(11)61849-7. PMID 22549046.
- ↑ Legrand-Abravanel F, Thevenet I, Mansuy JM, Saune K, Vischi F, Peron JM; et al. (2009). "Good performance of immunoglobulin M assays in diagnosing genotype 3 hepatitis E virus infections". Clin Vaccine Immunol. 16 (5): 772–4. doi:10.1128/CVI.00438-08. PMC 2681577. PMID 19321696.
- ↑ Pischke S, Suneetha PV, Baechlein C, Barg-Hock H, Heim A, Kamar N; et al. (2010). "Hepatitis E virus infection as a cause of graft hepatitis in liver transplant recipients". Liver Transpl. 16 (1): 74–82. doi:10.1002/lt.21958. PMID 19866448.
- ↑ Baylis SA, Hanschmann KM, Blümel J, Nübling CM, HEV Collaborative Study Group (2011). "Standardization of hepatitis E virus (HEV) nucleic acid amplification technique-based assays: an initial study to evaluate a panel of HEV strains and investigate laboratory performance". J Clin Microbiol. 49 (4): 1234–9. doi:10.1128/JCM.02578-10. PMC 3122834. PMID 21307208.
- ↑ 7.0 7.1 7.2 Aggarwal R, Jameel S (2011). "Hepatitis E." Hepatology. 54 (6): 2218–26. doi:10.1002/hep.24674. PMID 21932388.