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==Overview==
==Overview==
[[Liver function test]]s for assessment of severity of the disease.
There are no diagnostic [[laboratory]] findings exclusively associated with portal hypertension. Laboratory findings related with the diagnosis of [[cirrhosis]], as the most common underlying disease for portal hypertension, include indirect serum markers and direct [[fibrosis]] markers. Indirect serum markers are [[platelet count]], [[AST]]/[[ALT]] index, [[AST]]/[[platelet]] ratio index, and Lok score. Direct [[fibrosis]] markers are fibrotest, fibrometer, hepascore, [[hyaluronic acid]], and enhanced liver [[fibrosis]].
 
==Laboratory Findings==
*There are no diagnostic [[laboratory]] findings exclusively associated with portal hypertension.
*Laboratory findings related with the diagnosis of [[cirrhosis]], as the most common underlying disease for portal hypertension, include indirect serum markers and direct fibrosis markers.
 
=== Indirect serum markers ===
 
==== Platelet count ====
* Reduced [[platelet count]] is the most frequent test used to diagnose portal hypertension in [[chronic liver disease]].<ref name="pmid23058320">{{cite journal |vauthors=Berzigotti A, Seijo S, Arena U, Abraldes JG, Vizzutti F, García-Pagán JC, Pinzani M, Bosch J |title=Elastography, spleen size, and platelet count identify portal hypertension in patients with compensated cirrhosis |journal=Gastroenterology |volume=144 |issue=1 |pages=102–111.e1 |year=2013 |pmid=23058320 |doi=10.1053/j.gastro.2012.10.001 |url=}}</ref>
* 78% of the patients with [[cirrhosis]] have [[thrombocytopenia]].<ref name="pmid19281860">{{cite journal |vauthors=Qamar AA, Grace ND, Groszmann RJ, Garcia-Tsao G, Bosch J, Burroughs AK, Ripoll C, Maurer R, Planas R, Escorsell A, Garcia-Pagan JC, Patch D, Matloff DS, Makuch R, Rendon G |title=Incidence, prevalence, and clinical significance of abnormal hematologic indices in compensated cirrhosis |journal=Clin. Gastroenterol. Hepatol. |volume=7 |issue=6 |pages=689–95 |year=2009 |pmid=19281860 |pmc=4545534 |doi=10.1016/j.cgh.2009.02.021 |url=}}</ref>
* The probability of [[esophageal varices]] are low when the [[platelet count]] is normal.<ref name="pmid26047908">{{cite journal |vauthors=de Franchis R |title=Expanding consensus in portal hypertension: Report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension |journal=J. Hepatol. |volume=63 |issue=3 |pages=743–52 |year=2015 |pmid=26047908 |doi=10.1016/j.jhep.2015.05.022 |url=}}</ref>
 
==== AST/ALT index ====
* The [[AST]]/[[ALT]] ratio was first described by De Ritis, known also as De Ritis ratio.<ref name="pmid13447217">{{cite journal |vauthors=DE RITIS F, COLTORTI M, GIUSTI G |title=An enzymic test for the diagnosis of viral hepatitis; the transaminase serum activities |journal=Clin. Chim. Acta |volume=2 |issue=1 |pages=70–4 |year=1957 |pmid=13447217 |doi= |url=}}</ref>
* Elevated levels of [[AST]]/[[ALT]] index reflects the hepatocellular damage or death.<ref name="pmid24353357">{{cite journal| author=Botros M, Sikaris KA| title=The de ritis ratio: the test of time. | journal=Clin Biochem Rev | year= 2013 | volume= 34 | issue= 3 | pages= 117-30 | pmid=24353357 | doi= | pmc=3866949 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24353357  }}</ref>
* The [[AST]]/[[ALT]] ratio of more than 1 in [[chronic hepatitis]] is suggestive of [[cirrhosis]].<ref name="pmid3135226">{{cite journal |vauthors=Williams AL, Hoofnagle JH |title=Ratio of serum aspartate to alanine aminotransferase in chronic hepatitis. Relationship to cirrhosis |journal=Gastroenterology |volume=95 |issue=3 |pages=734–9 |year=1988 |pmid=3135226 |doi= |url=}}</ref>
 
==== AST/platelet ratio index ====
* Since both [[AST]] and [[platelet count]] are predictors of [[cirrhosis]] and [[fibrosis]] in [[liver]], [[AST]] to [[platelet]] ratio index (APRI) is postulated to multiply the diagnostic value.
* The APRI is significantly correlated with the stage of [[fibrosis]] in [[liver]], more than [[AST]] or [[platelet]] count separately.
<br>
<math display="block">APRI = [(AST/ULN)/platelet count(10^{9}/L)] \times 100</math><small>ULN= Upper limit of normal</small>
<br>
 
* APRI ≤ 0.50 is suggestive of absence of fibrosis and APRI > 1.50 is suggestive of presence of the significant [[fibrosis]].<ref name="pmid12883497">{{cite journal |vauthors=Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS, Lok AS |title=A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C |journal=Hepatology |volume=38 |issue=2 |pages=518–26 |year=2003 |pmid=12883497 |doi=10.1053/jhep.2003.50346 |url=}}</ref>
 
==== Lok ====
* The best [[serologic]] test for portal hypertension and [[esophageal varices]] is Lok score.
* The score is calculated through following formula: <ref name="pmid15986415">{{cite journal |vauthors=Lok AS, Ghany MG, Goodman ZD, Wright EC, Everson GT, Sterling RK, Everhart JE, Lindsay KL, Bonkovsky HL, Di Bisceglie AM, Lee WM, Morgan TR, Dienstag JL, Morishima C |title=Predicting cirrhosis in patients with hepatitis C based on standard laboratory tests: results of the HALT-C cohort |journal=Hepatology |volume=42 |issue=2 |pages=282–92 |year=2005 |pmid=15986415 |doi=10.1002/hep.20772 |url=}}</ref>
<br>
<math display="block">\log_{Predicting Cirrhosis}= -5.56 -0.0089 \times platelet (\times10^{3}/mm^3) + 1.26\times AST/ALT ratio + 5.27 \times INR</math>
<br>
* The Lok score of more than 0.73 is suggesting [[fibrosis]] and [[cirrhosis]] of the [[liver]].<ref name="pmid25732434">{{cite journal |vauthors=Procopet B, Cristea VM, Robic MA, Grigorescu M, Agachi PS, Metivier S, Peron JM, Selves J, Stefanescu H, Berzigotti A, Vinel JP, Bureau C |title=Serum tests, liver stiffness and artificial neural networks for diagnosing cirrhosis and portal hypertension |journal=Dig Liver Dis |volume=47 |issue=5 |pages=411–6 |year=2015 |pmid=25732434 |doi=10.1016/j.dld.2015.02.001 |url=}}</ref>
 
==== FIB-4 ====
* [[Fibrosis]]-4 (FIB-4) index is a simple non-invasive [[serologic]] method for diagnosing the [[fibrosis]] and [[cirrhosis]] in [[liver]].
* The FIB-4 index is calculated through following formula:
<br>
<math display="block">FIB-4 = Age \times AST [U/L]/ \sqrt{platelet [10^9]\times ALT[U/L]}</math>
<br>
 
* FIB-4 index of less than 1.6 excludes the [[cirrhosis]], while FIB-4 more than 3.6 is diagnostic of [[cirrhosis]].<ref name="KimKim2010">{{cite journal|last1=Kim|first1=Beom Kyung|last2=Kim|first2=Do Young|last3=Park|first3=Jun Yong|last4=Ahn|first4=Sang Hoon|last5=Chon|first5=Chae Yoon|last6=Kim|first6=Ja Kyung|last7=Paik|first7=Yong Han|last8=Lee|first8=Kwan Sik|last9=Park|first9=Young Nyun|last10=Han|first10=Kwang Hyub|title=Validation of FIB-4 and comparison with other simple noninvasive indices for predicting liver fibrosis and cirrhosis in hepatitis B virus-infected patients|journal=Liver International|volume=30|issue=4|year=2010|pages=546–553|issn=14783223|doi=10.1111/j.1478-3231.2009.02192.x}}</ref>
 
==== Forns ====
* The Forns score is designated for diagnosing mild [[fibrosis]] in cirrhotic patients.
* Forns [[fibrosis]] score is calculated using 4 factors of [[platelet count]], [[Gamma glutamyl transferase|gamma glutamyl transferase (GGT)]], [[age]], and [[cholesterol]] level.
<br>
<math display="block">Forns = 7.8111 - 3.131 \times\ln (platelet) + 0.781 \times \ln (GTT)+3.467\times \ln (age) - 0.014 \times (cholesterol)</math>
<br>
* Forns score of less than 4.2 excludes severe [[fibrosis]] in cirrhotic patients, with a reliable [[Negative predictive value|negative predictive value (NPV)]].<ref name="Forns2002">{{cite journal|last1=Forns|first1=X|title=Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model|journal=Hepatology|volume=36|issue=4|year=2002|pages=986–992|issn=02709139|doi=10.1053/jhep.2002.36128}}</ref>
 
=== Direct fibrosis markers ===
 
==== Fibrotest ====
* Fibrotest is a simple non-invasive test which is exclusively for [[liver]] [[fibrosis]] measurement, suggested by [[WHO]].<ref name="urlBioPredictive Library - FibroTest Publications">{{cite web |url=http://library.biopredictive.com/article/325/ |title=BioPredictive Library - FibroTest Publications |format= |work= |accessdate=}}</ref>
* Calculation of fibrotest is through 5 factors including [[Gamma-glutamyltransferase|GGT]], total [[bilirubin]] (bili), [[Alpha 2-macroglobulin|alpha-2-macroglobulin]] (A2MG), [[apolipoprotein A1]] (ApoA1), and [[haptoglobin]] (HG).
<br>
<small>
<math display="block">FibroTest = 4.467\times\log_{10} [A2MG(g/L)] - 1.357 \times log_{10} [HG(g/L)] + 1.017 \times log_{10}[GMT(IU/L)] + 0.0281 \times[age(years)] + 1.737 \times log_{10} [Bili( \mu mol/L)] -1.184 \times[ApoA1(g/L)] + 0.301 \times sex - 5.54 </math><small>Sex: (female= 0, male= 1)</small>
<br>
</small>
* Fibrotest score of less than 0.1 suggests very mild or absence of fibrosis and score of more than 0.6 strongly revealed moderate to severe fibrosis.<ref name="urlcdn.intechopen.com">{{cite web |url=http://cdn.intechopen.com/pdfs-wm/18776.pdf |title=cdn.intechopen.com |format= |work= |accessdate=}}</ref>
 
==== Fibrometer ====
* Fibrometer score is a non-invasive test for diagnosing severe stages of [[fibrosis]] among patients with [[cirrhosis]] and portal hypertension.<ref name="CasteraVilgrain2013">{{cite journal|last1=Castera|first1=Laurent|last2=Vilgrain|first2=Valérie|last3=Angulo|first3=Paul|title=Noninvasive evaluation of NAFLD|journal=Nature Reviews Gastroenterology & Hepatology|volume=10|issue=11|year=2013|pages=666–675|issn=1759-5045|doi=10.1038/nrgastro.2013.175}}</ref>
* Calculating fibrometer is by means of seven factors, including [[glucose]] (Glc), [[ferritin]], [[platelet count]], [[ALT]], [[Body weight|body weight (BW)]], and [[age]].
<br>
<small>
<math display="block">FibroMeter = 0.4184 \times Glc [mmol/L] + 0.0701 \times AST [U/L] + 0.00008 \times ferritin [\mu g/L] - 0.0102 \times platelet [g/L] - 0.0260 \times ALT [U/L] + 0.0459 \times BW [kg] + 0.0842 \times age [years] + 11.6226 </math>
</small>
<br>
* FibroMeter score of less than 0.36 reveals absence of significant [[fibrosis]], and score of more than 0.36 is suggestive of dramatic [[fibrosis]].<ref name="urlcdn.intechopen.com" />
 
==== Hepascore ====
* Hepascore is a scale for determining the level of [[fibrosis]] in [[liver]].
* The hepascore calculation is consisted of multiple factors, such as [[Alpha-2-Macroglobulin|A2MG]], [[hyaluronic acid]], [[Gamma-glutamyltransferase|GGT]], total [[bilirubin]], along with [[age]] and sex.<ref name="pmid6055434">{{cite journal |vauthors=Pereira HG, Tumova B, Webster RG |title=Antigenic relationship between influenza A viruses of human and avian origins |journal=Nature |volume=215 |issue=5104 |pages=982–3 |year=1967 |pmid=6055434 |doi= |url=}}</ref>
<br>
<math display="block">Logistic regression = y = \exp [-4.185818-(0.0249 \times age) + (0.7464 \times sex) + (1.0039\times A2MG) + (0.032 \times hyaluronic acid) + (0.0691 \times bilirubin) -(0.0012 \times GGT)]</math>
<br>
 
<math display="block">HepaScore= \tfrac{y}{y+1} </math>
<br>
* The cut-off point of 0.84 is set for [[diagnosis]] of [[cirrhosis]] in patients with portal hypertension.<ref name="urlcdn.intechopen.com" />
 
==== Hyaluronic acid ====
* [[Hyaluronic acid]] is a non-routine test for diagnosis of [[cirrhosis]] ([[sensitivity]] 78%, [[specificity]] 88%).
* In a patient with cirrhotic liver the plasma level of [[hyaluronic acid]] is increased up to 2 to 10-fold.<ref name="urlcdn.intechopen.com" />
* The cut-off point for [[hyaluronic acid]] is 60 μg/L.
 
==== Enhanced liver fibrosis ====
*Enhanced liver [[fibrosis]] (ELF) score is shows a reasonable correlation with the stage of [[fibrosis]] in [[chronic liver disease]].
*ELF score is calculated by means of [[Tissue inhibitor of metalloproteinases|tissue inhibitor of metalloproteinases 1]] (TIMP-1), amino-terminal [[propeptide]] of type III [[procollagen]] (PIIINP), and [[hyaluronic acid]] (HA).
<br>
<math display="block">ELF score = 2.494+ 0.846 \times \ln (HA) + 0.735 \times \ln (PIIINP) + 0.391\times\ln (TIMP-1) </math>
<br>
*The reference point for ELF score is 6.72 and the variable of '[[age]]' found to be the most effective factor on the score.<ref name="LichtinghagenPietsch2013">{{cite journal|last1=Lichtinghagen|first1=Ralf|last2=Pietsch|first2=Daniel|last3=Bantel|first3=Heike|last4=Manns|first4=Michael P.|last5=Brand|first5=Korbinian|last6=Bahr|first6=Matthias J.|title=The Enhanced Liver Fibrosis (ELF) score: Normal values, influence factors and proposed cut-off values|journal=Journal of Hepatology|volume=59|issue=2|year=2013|pages=236–242|issn=01688278|doi=10.1016/j.jhep.2013.03.016}}</ref>
 
==References==
==References==
{{reflist|2}}
{{reflist|2}}
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Latest revision as of 17:50, 7 December 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Eiman Ghaffarpasand, M.D. [2]

Overview

There are no diagnostic laboratory findings exclusively associated with portal hypertension. Laboratory findings related with the diagnosis of cirrhosis, as the most common underlying disease for portal hypertension, include indirect serum markers and direct fibrosis markers. Indirect serum markers are platelet count, AST/ALT index, AST/platelet ratio index, and Lok score. Direct fibrosis markers are fibrotest, fibrometer, hepascore, hyaluronic acid, and enhanced liver fibrosis.

Laboratory Findings

  • There are no diagnostic laboratory findings exclusively associated with portal hypertension.
  • Laboratory findings related with the diagnosis of cirrhosis, as the most common underlying disease for portal hypertension, include indirect serum markers and direct fibrosis markers.

Indirect serum markers

Platelet count

AST/ALT index

AST/platelet ratio index


<math display="block">APRI = [(AST/ULN)/platelet count(10^{9}/L)] \times 100</math>ULN= Upper limit of normal

  • APRI ≤ 0.50 is suggestive of absence of fibrosis and APRI > 1.50 is suggestive of presence of the significant fibrosis.[7]

Lok


<math display="block">\log_{Predicting Cirrhosis}= -5.56 -0.0089 \times platelet (\times10^{3}/mm^3) + 1.26\times AST/ALT ratio + 5.27 \times INR</math>

FIB-4


<math display="block">FIB-4 = Age \times AST [U/L]/ \sqrt{platelet [10^9]\times ALT[U/L]}</math>

  • FIB-4 index of less than 1.6 excludes the cirrhosis, while FIB-4 more than 3.6 is diagnostic of cirrhosis.[10]

Forns


<math display="block">Forns = 7.8111 - 3.131 \times\ln (platelet) + 0.781 \times \ln (GTT)+3.467\times \ln (age) - 0.014 \times (cholesterol)</math>

Direct fibrosis markers

Fibrotest


<math display="block">FibroTest = 4.467\times\log_{10} [A2MG(g/L)] - 1.357 \times log_{10} [HG(g/L)] + 1.017 \times log_{10}[GMT(IU/L)] + 0.0281 \times[age(years)] + 1.737 \times log_{10} [Bili( \mu mol/L)] -1.184 \times[ApoA1(g/L)] + 0.301 \times sex - 5.54 </math>Sex: (female= 0, male= 1)

  • Fibrotest score of less than 0.1 suggests very mild or absence of fibrosis and score of more than 0.6 strongly revealed moderate to severe fibrosis.[13]

Fibrometer


<math display="block">FibroMeter = 0.4184 \times Glc [mmol/L] + 0.0701 \times AST [U/L] + 0.00008 \times ferritin [\mu g/L] - 0.0102 \times platelet [g/L] - 0.0260 \times ALT [U/L] + 0.0459 \times BW [kg] + 0.0842 \times age [years] + 11.6226 </math>

  • FibroMeter score of less than 0.36 reveals absence of significant fibrosis, and score of more than 0.36 is suggestive of dramatic fibrosis.[13]

Hepascore


<math display="block">Logistic regression = y = \exp [-4.185818-(0.0249 \times age) + (0.7464 \times sex) + (1.0039\times A2MG) + (0.032 \times hyaluronic acid) + (0.0691 \times bilirubin) -(0.0012 \times GGT)]</math>

<math display="block">HepaScore= \tfrac{y}{y+1} </math>

Hyaluronic acid

Enhanced liver fibrosis


<math display="block">ELF score = 2.494+ 0.846 \times \ln (HA) + 0.735 \times \ln (PIIINP) + 0.391\times\ln (TIMP-1) </math>

  • The reference point for ELF score is 6.72 and the variable of 'age' found to be the most effective factor on the score.[16]

References

  1. Berzigotti A, Seijo S, Arena U, Abraldes JG, Vizzutti F, García-Pagán JC, Pinzani M, Bosch J (2013). "Elastography, spleen size, and platelet count identify portal hypertension in patients with compensated cirrhosis". Gastroenterology. 144 (1): 102–111.e1. doi:10.1053/j.gastro.2012.10.001. PMID 23058320.
  2. Qamar AA, Grace ND, Groszmann RJ, Garcia-Tsao G, Bosch J, Burroughs AK, Ripoll C, Maurer R, Planas R, Escorsell A, Garcia-Pagan JC, Patch D, Matloff DS, Makuch R, Rendon G (2009). "Incidence, prevalence, and clinical significance of abnormal hematologic indices in compensated cirrhosis". Clin. Gastroenterol. Hepatol. 7 (6): 689–95. doi:10.1016/j.cgh.2009.02.021. PMC 4545534. PMID 19281860.
  3. de Franchis R (2015). "Expanding consensus in portal hypertension: Report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension". J. Hepatol. 63 (3): 743–52. doi:10.1016/j.jhep.2015.05.022. PMID 26047908.
  4. DE RITIS F, COLTORTI M, GIUSTI G (1957). "An enzymic test for the diagnosis of viral hepatitis; the transaminase serum activities". Clin. Chim. Acta. 2 (1): 70–4. PMID 13447217.
  5. Botros M, Sikaris KA (2013). "The de ritis ratio: the test of time". Clin Biochem Rev. 34 (3): 117–30. PMC 3866949. PMID 24353357.
  6. 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.
  7. Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS, Lok AS (2003). "A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C". Hepatology. 38 (2): 518–26. doi:10.1053/jhep.2003.50346. PMID 12883497.
  8. Lok AS, Ghany MG, Goodman ZD, Wright EC, Everson GT, Sterling RK, Everhart JE, Lindsay KL, Bonkovsky HL, Di Bisceglie AM, Lee WM, Morgan TR, Dienstag JL, Morishima C (2005). "Predicting cirrhosis in patients with hepatitis C based on standard laboratory tests: results of the HALT-C cohort". Hepatology. 42 (2): 282–92. doi:10.1002/hep.20772. PMID 15986415.
  9. Procopet B, Cristea VM, Robic MA, Grigorescu M, Agachi PS, Metivier S, Peron JM, Selves J, Stefanescu H, Berzigotti A, Vinel JP, Bureau C (2015). "Serum tests, liver stiffness and artificial neural networks for diagnosing cirrhosis and portal hypertension". Dig Liver Dis. 47 (5): 411–6. doi:10.1016/j.dld.2015.02.001. PMID 25732434.
  10. Kim, Beom Kyung; Kim, Do Young; Park, Jun Yong; Ahn, Sang Hoon; Chon, Chae Yoon; Kim, Ja Kyung; Paik, Yong Han; Lee, Kwan Sik; Park, Young Nyun; Han, Kwang Hyub (2010). "Validation of FIB-4 and comparison with other simple noninvasive indices for predicting liver fibrosis and cirrhosis in hepatitis B virus-infected patients". Liver International. 30 (4): 546–553. doi:10.1111/j.1478-3231.2009.02192.x. ISSN 1478-3223.
  11. Forns, X (2002). "Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model". Hepatology. 36 (4): 986–992. doi:10.1053/jhep.2002.36128. ISSN 0270-9139.
  12. "BioPredictive Library - FibroTest Publications".
  13. 13.0 13.1 13.2 13.3 "cdn.intechopen.com" (PDF).
  14. Castera, Laurent; Vilgrain, Valérie; Angulo, Paul (2013). "Noninvasive evaluation of NAFLD". Nature Reviews Gastroenterology & Hepatology. 10 (11): 666–675. doi:10.1038/nrgastro.2013.175. ISSN 1759-5045.
  15. Pereira HG, Tumova B, Webster RG (1967). "Antigenic relationship between influenza A viruses of human and avian origins". Nature. 215 (5104): 982–3. PMID 6055434.
  16. Lichtinghagen, Ralf; Pietsch, Daniel; Bantel, Heike; Manns, Michael P.; Brand, Korbinian; Bahr, Matthias J. (2013). "The Enhanced Liver Fibrosis (ELF) score: Normal values, influence factors and proposed cut-off values". Journal of Hepatology. 59 (2): 236–242. doi:10.1016/j.jhep.2013.03.016. ISSN 0168-8278.

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